text stringlengths 559 401k | source stringlengths 13 121 |
|---|---|
Science and Islam (2009) is a three-part BBC documentary about the history of science in medieval Islamic civilization presented by Jim Al-Khalili. The series is accompanied by the book Science and Islam: A History written by Ehsan Masood.
== Episodes ==
"The Language of Science"
"The Empire of Reason"
"The Power of Doubt"
== Interviews ==
The documentary contains several short segments with scientists and historians of science:
George Saliba
Simon Schaffer
Peter Pormann (medicine)
Amira K. Bennison
Okasha El Daly (egyptology)
Ian Stewart (algebra)
Nader El-Bizri
== See also ==
List of Islamic films
== External links ==
Science and Islam at BBC Online
Science and Islam at IMDb
"The Language of Science"
"The Empire of Reason"
"The Power of Doubt"
"Medieval Islam Influences", Reel Truth Science Documentaries.
"Ibn al-Haytham & Optics", Reel Truth Science Documentaries.
"Islamic Knowledge", Reel Truth Science Documentaries. | Wikipedia/Science_and_Islam_(documentary) |
The Bahá'í Faith teaches that there is a harmony or unity between science and religion, and that true science and true religion can never conflict. This principle is rooted in various statements in the Bahá'í scriptures. Some scholars have argued that ideas in the philosophy of science resonate with the Bahá'í approach. In addition, scholars have noted the Bahá'í view of interpreting religious scriptures symbolically rather than literally as conducive to harmony with scientific findings. The Bahá'í community and leadership have also applied their teachings on science and religion with the goal of the betterment of society, for instance by providing education and technology.
== The principle of the harmony of science and religion ==
The principle of the harmony of science (or reason) and religion (or faith) has been a verbalized principle of the religion since ʻAbdu'l-Bahá's journeys to the West from 1910 to 1913 as an extension of the view of the singularness of reality to be explored through independent investigations by reasoned and spiritual methods. It had been discussed without the specific wording a decade earlier via a compilation Anton Haddad put together with Mírzá Abu'l-Faḍl along with their own perspective - a subject that was subsequently taken up by American Bahá'ís. Saiedi characterizes the relationship between science and the Bahá'í Faith, and the Bahá'í Faith and the importance of reason, as "one of its main spiritual principles."
The Bahá'í view of science has been summarized as emphasizing recognition of the process of science, although not one isolated to the "scientific method" from a set of values and societal choices and understandings, not mere faith in the conclusions which are always open to refinement, without casting so much doubt that the process of science is somehow lacking because it is influenced by current understandings and conditions to which religion can have a strong influence.
'Abdu'l-Bahá told jokes at the expense of materialist scientists. However, according to Phelps, he reserved his harshest condemnations for religious people who took religious scripture literally, who he said "…have become the cause of much of the conflict in the world, whether between different faith communities or between science and religion…"
=== In the Bahá'í writings ===
While writing on the Bahá'í views on science, certain excerpts from Bahá'í scriptures are commonly used by experts; the following are a few examples.
Nader Saiedi, adjunct professor at UCLA, notes Bahá'u'lláh criticized a pursuit of pseudoscience which claimed that "…numerous esoteric sciences is required to understand the mysteries of the sacred Word."
Phelps quotes Bahá'u'lláh on the issue of language and understanding:
[S]ince all do not possess the same degree of spiritual understanding, certain statements will inevitably be made, and there shall arise, as a consequence, as many differing opinions as there are human minds and as many divergent beliefs as there are created things. This is certain and settled, and can in no wise be averted…. Our aim is that thou shouldst urge all the believers to show forth kindness and mercy and to overlook certain shortcomings among them, that differences may be dispelled; true harmony be established; and the censure and reproach, the hatred and dissension, seen among the peoples of former times may not arise anew.
'Abdu'l-Bahá anonymously published The Secret of Divine Civilization in 1875 in Iran, noting how the country had declined among the nations "as a result of poor education, bad governance, ignorance of scientific advances, rejection of innovation, and the atrophy of the life of the mind." and later restated Bahá'u'lláh's teaching, saying:
Religious teaching which is at variance with science and reason is human invention and imagination unworthy of acceptance, for the antithesis and opposite of knowledge is superstition born of the ignorance of man. If we say religion is opposed to science, we lack knowledge of either true science or true religion, for both are founded upon the premises and conclusions of reason, and both must bear its test.” (The Promulgation of Universal Peace)
Religion and science are the two wings upon which man’s intelligence can soar into the heights, with which the human soul can progress. It is not possible to fly with one wing alone! Should a man try to fly with the wing of religion alone he would quickly fall into the quagmire of superstition, whilst on the other hand, with the wing of science alone he would also make no progress, but fall into the despairing slough of materialism. (Paris Talks )
Scientific knowledge is the highest attainment upon the human plane, for science is the discoverer of realities. It is of two kinds: material and spiritual. Material science is the investigation of natural phenomena; divine science is the discovery and realization of spiritual verities. The world of humanity must acquire both. (The Promulgation of Universal Peace)
Shoghi Effendi, head of the religion 1921–1957, offered a vision of the future including this principle:
In such a world society, science and religion, the two most potent forces in human life, will be reconciled, will co-operate, and will harmoniously develop…. The economic resources of the world will be organized, its sources of raw materials will be tapped and fully utilized, its markets will be co-ordinated and developed, and the distribution of its products will be equitably regulated. (World Order of Bahá'u'lláh)
The Bahá'í International Community released a statement in 1995, The Prosperity of Humankind which says in part:
For the vast majority of the world’s population, the idea that human nature has a spiritual dimension—indeed that its fundamental identity is spiritual—is a truth requiring no demonstration. It is a perception of reality that can be discovered in the earliest records of civilization and that has been cultivated for several millennia by every one of the great religious traditions of humanity’s past. Its enduring achievements in law, the fine arts, and the civilizing of human intercourse are what give substance and meaning to history. In one form or another its promptings are a daily influence in the lives of most people on earth and, as events around the world today dramatically show, the longings it awakens are both inextinguishable and incalculably potent.
and further:
Future generations … will find almost incomprehensible the circumstance that, in an age paying tribute to an egalitarian philosophy and related democratic principles, development planning should view the masses of humanity as essentially recipients of benefits from aid and training. Despite acknowledgment of participation as a principle, the scope of the decision making left to most of the world’s population is at best secondary, limited to a range of choices formulated by agencies inaccessible to them and determined by goals that are often irreconcilable with their perceptions of reality.
The scholar Graham Hassall summarizes that statement saying it "demonstrates the breath-taking scope of the Bahá'í program of governance reform, from local to global levels, and encompasses not only political and legal fundamentals, but the roles of science and technology in the global distribution of knowledge and power." and university professor Sabet Behrooz called "…a brilliant statement … (showing) the necessity of harmony between science and religion …(which) must be the guiding light and the organizing principle of our endeavors in integrative studies of the Bahá'í Faith."
== Implications ==
A number of scholars have offered commentary on the Bahá'í teachings on science and religion. Saiedi outlines several implications of the Bahá'í view of an agreement between religion and science or reason:
religious evolution of understanding laws and institutions.
religion is not a substitute or competition with science but have a mutual reciprocity because of their individual qualities
rather than take religious statements literally, the Bahá'í Faith provides a lexicon of interpretations or allegorical relationships of past statements
an acceptance of the laws of nature as an expression of divine will and so called miracles are not evidence otherwise.
Phelps lists the following three points:
that ultimate reality is ineffable
that humility about what can be understood and applied is itself "the highest degree of human attainment"
that religious scripture is metaphorical, not literal.
Farzam Arbab, project developer and Bahá'í administrator, also states that religious literalism is a problem.
Ian Kluge, independent scholar, observed a relationship between the Bahá'í stance of science and reason and the Bahá'í teaching on independent investigation for the individual where without reason and faith together, quoting `Abdu'l-Bahá, "...the heart finds no rest in it, and real faith is impossible..." and beyond the individual to societal progress which would be "...trapped in traditional worldviews or paradigms, be they religious, cultural, intellectual, or scientific..." and appealed to Aristotle’s four-fold causality which to him "...suggests that science deals with material and efficient causality whereas religion deals with issues related to formal and final causality."
Scholars have also drawn parallels between Bahá'í views of science and the views of various philosophers. Karlberg and Smith underscore and summarize the work of Alan Chalmers and Peter Godfrey-Smith who had published university press texts, in relation to the Bahá'í Faith on a number of points. Arbab appealed to Thomas Nagel's thoughts on "sophisticated secularism." Roland Faber elaborated this approach in parallel with the philosophy of Alfred North Whitehead (so-called Process philosophy) and William S. Hatcher drew on the ideas of Aristotle, Avicenna, Bertrand Russell, and Stephen Hawking in his defence of the Bahá'í view.
Sociologist Margit Warburg quotes a 1978 letter from the Universal House of Justice "The principle of the harmony of science and religion means not only that religious teachings should be studied with the light of reason and evidence as well as of faith and inspiration, but also that everything in this creation, all aspects of human life and knowledge, should be studied in light of revelation as well as in that of purely rational investigation." From it Warburg sees a "clear stance in the dilemma between academic freedom and acceptance of religious premises" and the issues of where "possible conflict with doctrines that can be tested empirically" can occur. She notes that at the inauguration of the chair for Bahá'í Studies at Hebrew University of Jerusalem, Peter Khan spoke saying in part that the place of Bahá'í understanding between science and religion was not in the "narrow definitions of legitimate scholarly activity in some disciplines within the academic community" criticizing the materialistic scientific studies of religion, asking that Bahá'í scholars, in Warburg's words, "should not comply with their academic tradition" which ignore the spiritual inputs of religion which will conflict with the Bahá'í Faith's own teachings. Warburg criticizes Khan's statement as a spokesman of the Bahá'í Faith in this situation and what it could mean for Bahá'í administration. "That is precisely what is at stake in the case of the controversial sources to Babi and Baha’i history, as well as concerning the sources to the construction of Abraham."
Behrooz Sabet proposed a review of the progressive nature of religion and scholarly activity with history and present contexts in 2000. He stated that "An integrative approach to understanding the implications of the Bahá'í teachings, however, follows developmental processes that begin as primarily internal and evolve in a direction of externalization and fusion with other branches of knowledge. Historically, religions show a similarity of patterns in the development of learning and scholarship methods. For instance, in earlier configurations of integrative studies, a conflict between internal and external is unavoidable since the internal values of the emerging religion are based on a prescriptive (or declarative) style of thinking that presupposes the existence of an inherent circle of unity among its teachings, while the dominant mode of scholarship in the scientific and academic community may view the validity of those presuppositions untenable. Generally speaking, absolutist positions and authoritarian attitudes expressed by the gatekeepers of knowledge in both science and religion have obscured people's clarity of vision and hindered the union of these two essential entities of human life. In the Bahá'í view, universal teachings of religion should be interpreted within the context of the relativity of human comprehension and the historical nature of knowledge."
== Applications ==
Others have addressed the work of a relationship between science and religion in practical expressions of development. Matthew Weinberg and Arbab, Boicu and Zabihi-Maghaddam, reviewed cases of a social engagement in locally meaningful progress that included a cooperative engagement between religion and science in particular processes.
The influence of the Bahá'í teaching on science and religion was visible in the practice of the religion dating back to the 1870s in the face of a perception of a lot of superstition of Iranian society and taking a stance towards education, science, and technology. Scholars Filip Boicu and Siyamak Zabihi-Maghaddam underscored the Bahá'í view on education directly related to this teaching of the religion which led to some early Bahá'í schools in Iran. Boicu and Zabihi-Maghaddam, recalling the Bahá'í experience in Iran on early schooling which had been extended about education of girls, followed developments of three models of education - Anisa, FUNDAEC, and the Core Curriculum - all of which had direct applications of the teaching and only being distinguished on the application between the individual alone, the individual in a society, and the last one being of all people in the whole of society and a global community.
In the early 20th century, as the Bahá'í Faith was expanding in the United States, the Bahá'í community viewed the issue of race according to another Bahá'í principle – the oneness of humanity – which had been expressed earlier but was further substantiated by 1912 during `Abdu'l-Bahá's talks to American audiences. The idea of interracial unity was counter to views of the majority of scientists of the coming decades and for a time in government policies, which endorsed eugenics as legal steps against Indigenous Americans, people of African descent, and generally People of Color, and other practices according to white-society standards, and similarly in other countries such as when the religion was banned in Germany under the Nazis. However, the American Bahá'í community did not respond by denigrating the scholarly thought of the day, but rather by supporting the then-minority view of scholars who opposed scientific racism. Marion Carpenter, a notable early American Bahá'í youth, is quoted in 1925 saying “Not religion or science, but religion and science, the combination of faith and reason, is the teaching of Bahá’u’lláh to the world today.” The American scientist Herbert Miller defended interracial unity at a Bahá'í-sponsored World Unity Conference in 1926 in Cleveland.
Project analyst Matthew Weinberg outlined socioeconomic development cases using the non-profit ISGP - the Institute for Studies for Global Prosperity, "a non-profit organization working in collaboration with the Baha’i International Community", in India, Uganda, and Brazil. In India stakeholders in a project developed an engagement of religion and science anchored in community of practice was seen as a majority point of view of the participants in the conference and the Indian National Spiritual Assembly established an office - the "Secretariat for the Promotion of the Discourse on Science, Religion, and Development" in 2001. They had successive meetings in 2004 and 2007 and ongoing. In Uganda work reached a point in 2001 working with IGSP that Ugandan president Yoweri Museveni encouraged the work of nurturing social unity "by championing the equality of women and men, alleviating poverty, and overcoming entrenched patterns of corruption." Again materialistic approaches were seen as failing alone. In Brazil again in 2001 a program of action was initiated, seminars were held and a group formed to develop analysis of the system published a book and simultaneously application in some local community "Centers of Learning" and one as a pilot project, but to advance the group needed to approach the work with some values: "To set out on a new path requires courage—not an arrogant disposition that demands swift and radical action, but one that is tempered with humility and wisdom. It requires an environment where the dynamics of individual and collective transformation are fully considered; where it is realized that growth and change are organic, that they are gradual and slow, and that they involve constant action, evaluation, and study; and where it is understood that, in pursuing such transformation, one is faced with an ongoing tension between absorbing setbacks and gaining new ground."
== Influence ==
Sociologist Michael McMullen found that Bahá'í converts in the United States appreciated the teaching of a harmony between science and religion as resolving their sense of these. They had been disillusioned with traditional organized religion but found that the Bahá'í Faith's use of science to inform religion "makes sense and provides meaning in a globalized world", and appreciated that the Bahá'í Faith had an evolutionary perspective on revelation via the teaching of progressive revelation. Post-doctoral scholar in Ottoman Studies and faculty at the Wilmette Institute, Necati Alkan documented the case of Muslim intellectual Abdullah Cevdet (1869–1932) in looking at the influence of the Bahá'í Faith and the teaching of the harmony of science and religion specifically as a model of reform but which was not accepted by the Turkish Muslim community.
== Bahá'í views on evolution ==
ʻAbdu'l-Bahá discussed evolution, including making claims that appear to contradict the modern doctrine of common descent for all earthly life. For example, in Some Answered Questions he said:
...from the beginning of man's existence on this planet until he assumed his present shape, form, and condition, a long time must have elapsed, and he must have traversed many stages before reaching his present condition. But from the beginning of his existence man has been a distinct species.
His teachings were widely interpreted as a kind of parallel evolution, in which humans had a separate line of descent to some primitive form, separate from animals. But the emphasis on the harmony of science and religion and the success of the modern evolutionary paradigm resulted in at least 19 books and articles from 16 authors over the period of 1990 to 2009 trying to address how Bahá'ís should view evolution in light of ʻAbdu'l-Bahá's statements, the majority of which took universal common ancestry as fact and attempted to reconcile with a new interpretation of the statements. Two articles by Keven Brown and Eberhard von Kitzing, jointly published under the title Evolution and Bahá'í Belief (2001), stand out as the only book-length review of the issue by Bahá'ís during the period, and has been well received.
The new understanding viewed the apparent meaning of parallel evolution as an unfortunate misunderstanding that should be carefully studied and interpreted in terms that make sense today. Gary Matthews wrote,
...the apparent contradiction is nothing more than a question of semantics: perhaps ʻAbdu'l-Bahá is merely dating man's beginning as a distinct species from the soul's first appearance, to emphasize that we do not derive our higher spiritual nature from our animal forebears."
This understanding was included in the Foreword to the 2014 printing of Some Answered Questions, stating:
...[ʻAbdu'l-Bahá's] concern is not with the mechanisms of evolution but with the philosophical, social, and spiritual implications of the new theory. His use of the term "species", for example, evokes the concept of eternal or permanent archetypes, which is not how the term is defined in contemporary biology. For Bahá'ís, the science of evolution is accepted..."
Not all Bahá'ís were convinced of the argument that ʻAbdu'l-Bahá's statements are in complete alignment with modern evolutionary theory. Salman Oskooi wrote his 2009 thesis on the subject and was unconvinced by the various authors trying to reconcile the issue with modern science, writing that ʻAbdu'l-Bahá's statements have an "apparent discord with science", "appear uninterpretable in any sense but their apparent meaning", and the apparent meaning is that "humans have been distinct from other beings since the time of some primitive stage of our evolution." Oskooi concluded that ʻAbdu'l-Bahá was fallible on scientific matters, but that the issue does not contradict the fundamental premise of the faith. Also in 2009, Ian Kluge wrote that, "There is no question that ʻAbdu'l-Bahá's views on human evolution are in conflict with current scientific thought", but he concluded that religion cannot "uncritically agree with science on all its pronouncements at all times" due to the changing nature of science itself.
According to Bahá'í philosopher Ali Murad Davoudi, Bahá'í holy writings rarely comment on scientific findings, and when they do, they are mostly aimed at refuting non-scientific and ideology-oriented results that some have deduced from science. As an example, ʻAbdu'l-Bahá's comments on evolution aim at refuting the prescription and justification of war, competition, and denial of the spiritual aspect of human being that some ideologies have deduced from evolution. In the foreword of Some Answered Questions a similar point is raised: "A careful review of ‘Abdu’l‑Bahá’s statements in this volume and in other sources suggests that His concern is not with the mechanisms of evolution but with the philosophical, social, and spiritual implications of the new theory. ... For Bahá’ís, the science of evolution is accepted, but the conclusion that humanity is merely an accidental branch of the animal kingdom—with all its attendant social implications—is not."
In 2023, Bryan Donaldson published On the Originality of Species, attempting to address the issue from the point of view of new research in evolutionary biology that could plausibly support the idea of "independent and parallel growth of many categories of plants and animals out of a network of gene-sharing unicellular roots." Donaldson points to a variety of trends in evolutionary thought since the late 1990s, concluding that,
...it is no longer necessary to conclude that the concept of independent or 'parallel' descent is incompatible with science. In fact, the trend of discovery has clearly been in the direction of agreement... This new understanding appears to me to have only been possible since about 2015.
== See also ==
Dialectic
== Notes ==
== Citations ==
== References ==
== Further reading ==
Filson, Gerald. Mind: ‘the Power of the Human Spirit'. Journal of Bahá’í Studies, vol. 32, no. 3-4, July 2023, pp. 9-53.
Phelps, Steven (2022). "Ch. 17: The harmony of science and religion". In Stockman, Robert H. (ed.). The World of the Bahá'í Faith. Oxfordshire, UK: Routledge. pp. 211–216. ISBN 978-1-138-36772-2. | Wikipedia/Baháʼí_Faith_and_science |
The Religious Society of Friends, commonly known as Quakers, encouraged some values which may have been conducive to encouraging scientific talents. A theory suggested by David Hackett Fischer in his book Albion's Seed indicated early Quakers in the US preferred "practical study" to the more traditional studies of Greek or Latin popular with the elite. Another theory suggests their avoidance of dogma or clergy gave them a greater flexibility in response to science.
Despite those arguments a major factor is agreed to be that the Quakers were initially discouraged or forbidden to go to the major law or humanities schools in Britain due to the Test Act. They also at times faced similar discriminations in the United States, as many of the colonial universities had a Puritan or Anglican orientation. This led them to attend "Godless" institutions or forced them to rely on hands-on scientific experimentation rather than academia.
Because of these issues it has been stated that Quakers are better represented in science than most religions. Some sources, including Pendlehill (Thomas 2000) and Encyclopædia Britannica, indicate that for over two centuries they were overrepresented in the Royal Society. Mention is made of this possibility in studies referenced in religiosity and intelligence and in a book by Arthur Raistrick. Regardless of whether this is still accurate, there have been several noteworthy members of this denomination in science.
Other notable scientists had Quaker backgrounds without being practicing Quakers themselves. These include John Bardeen, whose mother was a Quaker, and Karl Barry Sharpless, who attended a Quaker school and stated that Quaker values contributed to his success as a chemist. Together with Frederick Sanger (listed below), this means that three of the four individuals who as of 2023 have won two Nobel Prizes in science categories were raised by Quakers.
== Some Quakers in science ==
William Allen – more known for abolitionism and penal reform; a Fellow of the Royal Society and the Linnean Society of London
James Backhouse – botanist and missionary; author abbreviation "Backh"
Wilson Baker – organic chemist
John Bartram – described as the "father of American botany"; founded Bartram Botanical Gardens in Kingsessing on the bank of the Schuylkill River
Anna McClean Bidder – marine zoologist and first president of Lucy Cavendish College, Cambridge
Kenneth E. Boulding – systems theorist and economist
Russell Brain, 1st Baron Brain – neurologist known for Brain's reflex; became a Quaker in 1931 and gave the Swarthmore Lecture in 1944, "Man, Society and Religion", in which he stressed the importance of a social conscience
Jocelyn Bell Burnell – discovered the first radio pulsars with her thesis advisor Antony Hewish; raised Quaker in Northern Ireland; volunteered in local and national Quaker activities up to at least the 1970s; her Swarthmore Lecture was titled "Broken for Life"; still an active Quaker
John Cassin – ornithologist
Ezra Townsend Cresson – entomologist
Peter Collinson – botanist with some interest in electricity; his family belonged to the Gracechurch meeting of the Religious Society of Friends
Edward Drinker Cope – early paleontologist who took part in the Bone Wars and for whom Cope's Rule is named
John Dalton – taught at a Quaker school, but is best known for work in atomic theory.
Jeremiah Dixon – surveyor and astronomer known for the Mason–Dixon line
Henry Doubleday – horticulturist and lace designer
Arthur Stanley Eddington – astrophysicist known especially for the Eddington experiment and as a populariser of science, active in the Quaker Guild of Teachers, attended meetings regularly; his Swarthmore Lecture was titled "Science and the Unseen World"
George Ellis – co-authored The Large Scale Structure of Space-Time with University of Cambridge physicist Stephen Hawking; won the 2004 Templeton Prize and got involved with the Quaker Service Fund
John Fothergill – physician and botanist; Fothergilla (witch alder) is named for him
Robert Were Fox the Younger – geologist active in the early days of the British Association for the Advancement of Science
Ursula Franklin – metallurgist and physicist
George Graham – clockmaker and geophysicist who discovered the diurnal variation of the terrestrial magnetic field
John Gummere – astronomer
Richard Harlan – naturalist
Thomas Hodgkin – lived in the more ultra-orthodox era of Quakerism so wore plain clothes and spoke in a formal manner; Hodgkin's disease is named for him
Rush D. Holt, Jr. – Congressman; former assistant director of the Princeton Plasma Physics Laboratory; beat Watson; has a patent for a "method for maintaining a correct density gradient in a non-convecting solar pond"
Luke Howard – meteorologist known for work in cloud types and nomenclature
George Barker Jeffery – known for Jeffery's equations and translating works on the theory of relativity to English; his Swarthmore Lecture was "Christ, Yesterday and Today"
Isaac Lea – conchologist born a Quaker
Graceanna Lewis – ornithologist and social reformer
Joseph Jackson Lister – known for his role in the development of the optical microscope; his son, Joseph Lister, 1st Baron Lister, was a pioneer in surgical sterile techniques, but left the Quakers and joined the Scottish Episcopal Church
Kathleen Lonsdale – prominent crystallographer; discovered the planar hexagonal structure of benzene; became a Quaker in 1935, as such, she was a committed pacifist and served time in Holloway prison during World War II because she refused to register for civil defense duties or to pay the resulting fine; her Swarthmore Lecture was titled "Removing the Causes of War"
Maria Mitchell – astronomer who was raised as a Quaker but later adopted Christian Unitarianism
Frank Morley – mathematician specializing in algebra and geometry and known for Morley's trisector theorem. Was the son of two Quakers
Frederick Parker-Rhodes – plant pathologist and linguistics researcher, also active in other fields
William Philips – founder of the Geological Society of London
Lewis Fry Richardson – meteorologist; his Quaker beliefs exempted him from military service during World War I
Frederick Sanger – biochemist, two-time winner of the Nobel Prize in Chemistry; raised Quaker
Lucy Say – naturalist, nature artist, and first female member of the Academy of Natural Sciences of Philadelphia
Thomas Say – entomologist, conchologist, and herpetologist
Joseph Hooton Taylor, Jr. – astrophysicist and winner of the 1993 Nobel Prize in Physics for his discovery with Russell Alan Hulse of a "new type of pulsar, a discovery that has opened up new possibilities for the study of gravitation"
Silvanus P. Thompson – known for his book Calculus Made Easy; developed an idea of a telegraph submarine cable; his Swarthmore Lecture was titled "The Quest for Truth"
William Homan Thorpe – President of the British Ornithologists' Union from 1955 to 1960; his Swarthmore Lecture was titled "Quakers and Humanists"
Daniel Hack Tuke – expert on mental illness; came from a long line of Quakers from York who were interested in mental illness and concerned with those afflicted
Caspar Wistar – anatomist in colonial America
Thomas Young – polymath and child prodigy; raised Quaker.
== See also ==
List of Friends schools
List of Quakers
Relationship between religion and science
Christianity and science
== References ==
== Further reading ==
Quakers in Science and Industry by Arthur Raistrick. ISBN 1-85072-106-8
Thomas, Anne (April 24, 2000), This I Know Experimentally, Spring 2000 Monday Night Lecture Series: Science and Religion, Pendle Hill (published October 6, 2003), archived from the original on May 1, 2006, retrieved June 29, 2009 | Wikipedia/Quakers_in_science |
Rocks of Ages: Science and Religion in the Fullness of Life is a 1999 book about the relationship between science and religion by the Harvard paleontologist Stephen Jay Gould. First published by Ballantine Books, it was reprinted by Vintage Books. The book is a volume in the series, The Library of Contemporary Thought.
== Summary ==
Gould addresses the conflict between secular scientists and religious believers who question or deny scientific theory when it is in discrepancy with religious teachings on the origin and nature of the natural world. Borrowing a term from the Catholic Church, Gould describes science and religion as each comprise a separate magisterium of human understanding. Science defines the natural world, and religion the moral world. If each realm is separate, then according to Gould, they are not in conflict. He calls this the principle of non-overlapping magisteria, abbreviated NOMA.
== Reception ==
The book has been reviewed extensively, and commented on by both sides of the conflict he addresses.
== See also ==
Intelligent design
Richard Dawkins
Moral Landscape
== References ==
== External links ==
Rocks of Ages at Ballantine Books website | Wikipedia/Rocks_of_Ages:_Science_and_Religion_in_the_Fullness_of_Life |
The State of Tennessee v. John Thomas Scopes, commonly known as the Scopes trial or Scopes Monkey Trial, was an American legal case from July 10 to July 21, 1925, in which a high school teacher, John T. Scopes, was accused of violating the Butler Act, a Tennessee state law which outlawed the teaching of human evolution in public schools. The trial was deliberately staged in order to attract publicity to the small town of Dayton, Tennessee, where it was held. Scopes was unsure whether he had ever actually taught evolution, but he incriminated himself deliberately so the case could have a defendant. Scopes was represented by the American Civil Liberties Union, which had offered to defend anyone accused of violating the Butler Act in an effort to challenge the constitutionality of the law.
Scopes was found guilty and was fined $100 (equivalent to $1,800 in 2024), but the verdict was overturned on a technicality. William Jennings Bryan, a three-time presidential candidate and former secretary of state, argued for the prosecution, while famed labor and criminal lawyer Clarence Darrow served as the principal defense attorney for Scopes. The trial publicized the fundamentalist–modernist controversy, which set modernists, who believed evolution could be consistent with religion, against fundamentalists, who believed the word of God as revealed in the Bible took priority over all human knowledge. The case was thus seen both as a theological contest and as a trial on whether evolution should be taught in schools. The trial became a symbol of the larger social anxieties associated with the cultural changes and modernization that characterized the decade of the 1920s in the United States. It also served its purpose of drawing intense national publicity and highlighted the growing influence of mass media, having been covered by news outlets around the country and being the first trial in American history to be nationally broadcast by radio.
== Background and origins ==
=== Butler Act ===
Tennessee State Representative John Washington Butler, a Tennessee farmer and head of the World Christian Fundamentals Association, lobbied state legislatures to pass anti-evolution laws. He succeeded when the Butler Act was signed into law in Tennessee, on March 21, 1925. Butler later stated, "I didn't know anything about evolution ... I'd read in the papers that boys and girls were coming home from school and telling their fathers and mothers that the Bible was all nonsense." Tennessee governor Austin Peay signed the bill to gain support among rural legislators, but believed the law would neither be enforced nor interfere with education in Tennessee schools. William Jennings Bryan, who had been campaigning against the teaching of evolution in public schools, thanked Peay enthusiastically for the bill, stating "The Christian parents of the state owe you a debt of gratitude for saving their children from the poisonous influence of an unproven hypothesis." In response, the American Civil Liberties Union (ACLU) financed a test case by offering to defend anyone accused of teaching the theory of evolution in defiance of the Butler Act.
=== Planning ===
On April 5, 1925, George Rappleyea, the local manager for the Cumberland Coal and Iron Company, arranged a meeting with county superintendent of schools Walter White and local attorney Sue K. Hicks at Robinson's Drug Store in Dayton, convincing them that the controversy of such a trial would give Dayton much needed publicity. According to Robinson, Rappleyea said "As it is, the law is not enforced. If you win, it will be enforced. If I win, the law will be repealed. We're game, aren't we?" The men then summoned 24-year-old John T. Scopes, a Dayton high school science and math teacher. The group asked Scopes, who had substituted for the regular biology teacher, to admit to teaching the theory of evolution.
Rappleyea pointed out that, while the Butler Act prohibited the teaching of the theory of evolution, the state required teachers to use George William Hunter's textbook, Civic Biology: Presented in Problems, which explicitly described and endorsed the theory of evolution, as well as scientific racism and eugenics; and that teachers were, therefore, effectively required to break the law. Scopes mentioned that while he could not remember whether he had actually taught evolution in class, he had, however, gone through the evolution chart and respective chapter with the class. He told the group that he would be willing to stand trial if they could prove that he had taught evolution and could qualify as a defendant.
Scopes urged students to testify against him and coached them in their answers. Judge John T. Raulston accelerated the convening of the grand jury and "... all but instructed the grand jury to indict Scopes, despite the meager evidence against him and the widely reported stories questioning whether the willing defendant had ever taught evolution in the classroom". Scopes was charged on May 5 and indicted on May 25 for teaching from the chapter on evolution to a high school class in violation of the Butler Act, after three students testified against him to the grand jury. One student afterwards told reporters: "I believe in part of evolution, but I don't believe in the monkey business." Scopes was nominally arrested, though he was never actually detained. Paul Patterson, owner of The Baltimore Sun, put up $500 in bail for Scopes. The original prosecutors were Herbert E. and Sue K. Hicks, two brothers who were local attorneys and friends of Scopes, but the prosecution was ultimately led by Tom Stewart, the district attorney for the 18th Circuit who later became a U.S. Senator from Tennessee. Stewart was aided by Dayton attorney Gordon McKenzie, who supported the anti-evolution bill on religious grounds, and described evolution as "detrimental to our morality" and an assault on "the very citadel of our Christian religion."
Hoping to attract major press coverage, Rappleyea went so far as to write to British novelist H. G. Wells asking him to join the defense team. Wells replied that he had no legal training in Britain, let alone in America, and declined the offer. John R. Neal, a law school professor from Knoxville, announced that he would act as Scopes' attorney whether Scopes liked it or not, and he became the nominal head of the defense team. Baptist pastor William Bell Riley, the founder and president of the World Christian Fundamentals Association, was instrumental in calling lawyer and three-time Democratic presidential nominee, former United States Secretary of State, and lifelong Presbyterian William Jennings Bryan to act as that organization's counsel. Bryan had originally been invited by Sue Hicks to become an associate of the prosecution and Bryan had readily accepted, despite the fact he had not tried a case in thirty-six years. As Scopes pointed out to James Presley in the book Center of the Storm, on which the two collaborated: "After [Bryan] was accepted by the state as a special prosecutor in the case, there was never any hope of containing the controversy within the bounds of constitutionality."
Following the recruitment of Bryan, Clarence Darrow approached John Neal of the defense team and offered his services. Neal accepted, without consulting the rest of the team or the defendant himself. The ACLU had been seeking out an addition to the defense that would parallel Bryan's political experience, but had previously indicated that they did not want Darrow involved out of concern that his staunch agnosticism would imperil the defense team's case. Darrow later claimed he was motivated to join the defense after he "realized there was no limit to the mischief that might be accomplished unless the country was aroused to the evil at hand". After many changes back and forth, the defense team consisted of Darrow; ACLU attorney Arthur Garfield Hays; Dudley Field Malone, an international divorce lawyer who had worked at the State Department; W. O. Thompson, who was Darrow's law partner; and F. B. McElwee. The defense was also assisted by librarian and Biblical authority Charles Francis Potter, who was a modernist Unitarian preacher.
== Proceedings ==
The ACLU had originally intended to oppose the Butler Act on the grounds that it violated the teacher's individual rights and academic freedom, and was therefore unconstitutional. Principally because of Clarence Darrow, this strategy changed as the trial progressed. The earliest argument proposed by the defense once the trial had begun was that there was actually no conflict between evolution and the creation account in the Bible; later, this viewpoint would be called theistic evolution. In support of this claim, they brought in eight experts on evolution. But other than Maynard Metcalf, a zoologist from Johns Hopkins University, the judge would not allow these experts to testify in person. Instead, they were allowed to submit written statements so their evidence could be used at the appeal. In response to this decision, Darrow made a sarcastic comment to Judge Raulston (as he often did throughout the trial) on how he had been agreeable only on the prosecution's suggestions. Darrow apologized the next day, keeping himself from being found in contempt of court.
The presiding judge, John T. Raulston, was accused of being biased towards the prosecution and frequently clashed with Darrow. At the outset of the trial, Raulston quoted Genesis and the Butler Act. He also warned the jury not to judge the merit of the law (which would become the focus of the trial) but on the violation of the Act, which he called a 'high misdemeanor'. The jury foreman himself was unconvinced of the merit of the Act but he acted, as did most of the jury, on the instructions of the judge.
Bryan chastised evolution for teaching children that humans were but one of 35,000 types of mammals and bemoaned the notion that human beings were descended "Not even from American monkeys, but from old world monkeys".
Darrow responded for the defense in a speech that was universally considered the oratorical climax of the trial. Arousing fears of "inquisitions", Darrow argued that the Bible should be preserved in the realm of theology and morality and not put into a course of science. In his conclusion, Darrow declared that Bryan's "duel to the death" against evolution should not be made one-sided by a court ruling that took away the chief witnesses for the defense. Darrow promised there would be no duel because "there is never a duel with the truth." The courtroom went wild when Darrow finished; Scopes declared Darrow's speech to be the dramatic high point of the entire trial and insisted that part of the reason Bryan wanted to go on the stand was to regain some of his tarnished glory.
=== Examination of Bryan ===
On the sixth day of the trial, the defense ran out of witnesses. The judge declared that all the defense testimony on the Bible was irrelevant and should not be presented to the jury (which had been excluded during the defense). On the seventh day of the trial, the defense asked the judge to call Bryan as a witness to question him on the Bible, as their own experts had been rendered irrelevant; Darrow had planned this the day before and called Bryan a "Bible expert". This move surprised those present in the court, as Bryan was a counsel for the prosecution and Bryan himself (according to a journalist reporting the trial) never made a claim of being an expert, although he did tout his knowledge of the Bible. This testimony revolved around several questions regarding Biblical stories and Bryan's beliefs (as shown below); this testimony culminated in Bryan declaring that Darrow was using the court to "slur the Bible" while Darrow replied that Bryan's statements on the Bible were "foolish".
On the seventh day of the trial, Clarence Darrow took the unorthodox step of calling William Jennings Bryan, counsel for the prosecution, to the stand as a witness in an effort to demonstrate that belief in the historicity of the Bible and its many accounts of miracles was unreasonable. Bryan accepted, on the understanding that Darrow would in turn submit to questioning by Bryan. Although Hays would claim in his autobiography that the examination of Bryan was unplanned, Darrow spent the night before in preparation. The scientists the defense had brought to Dayton—and Charles Francis Potter, a modernist minister who had engaged in a series of public debates on evolution with the fundamentalist preacher John Roach Straton—prepared topics and questions for Darrow to address to Bryan on the witness stand. Kirtley Mather, chairman of the geology department at Harvard and also a devout Baptist, played Bryan and answered questions as he believed Bryan would. Raulston had adjourned court to the stand on the courthouse lawn, ostensibly because he was "afraid of the building" with so many spectators crammed into the courtroom, but probably because of the stifling heat.
==== Adam and Eve ====
An area of questioning involved the book of Genesis, including questions about whether Eve was actually created from Adam's rib, where Cain got his wife, and how many people lived in Ancient Egypt. Darrow used these examples to suggest that the stories of the Bible could not be scientific and should not be used in teaching science, telling Bryan, "You insult every man of science and learning in the world because he does not believe in your fool religion." Bryan's declaration in response was "The reason I am answering is not for the benefit of the superior court. It is to keep these gentlemen from saying I was afraid to meet them and let them question me, and I want the Christian world to know that any atheist, agnostic, unbeliever, can question me anytime as to my belief in God, and I will answer him."
Stewart objected for the prosecution, demanding to know the legal purpose of Darrow's questioning. Bryan, gauging the effect the session was having, snapped that its purpose was "to cast ridicule on everybody who believes in the Bible". Darrow, with equal vehemence, retorted "We have the purpose of preventing bigots and ignoramuses from controlling the education of the United States."
A few more questions followed in the charged open-air courtroom. Darrow asked where Cain got his wife; Bryan answered that he would "leave the agnostics to hunt for her". When Darrow addressed the issue of the temptation of Eve by the serpent, Bryan insisted that the Bible be quoted verbatim rather than allowing Darrow to paraphrase it in his own terms. However, after another angry exchange, Judge Raulston banged his gavel, adjourning the court.
==== End of the trial ====
The confrontation between Bryan and Darrow lasted approximately two hours on the afternoon of the seventh day of the trial. It is likely that it would have continued the following morning but for Judge Raulston's announcement that he considered the whole examination irrelevant to the case and his decision that it should be "expunged" from the record. Thus Bryan was denied the chance to cross-examine the defense lawyers in return, although after the trial Bryan would distribute nine questions to the press to bring out Darrow's "religious attitude". The questions and Darrow's short answers were published in newspapers the day after the trial ended, with The New York Times characterizing Darrow as answering Bryan's questions "with his agnostic's creed, 'I don't know,' except where he could deny them with his belief in natural, immutable law".
After the defense's final attempt to present evidence was denied, Darrow asked the judge to bring in the jury only to have them come to a guilty verdict:
We claim that the defendant is not guilty, but as the court has excluded any testimony, except as to the one issue as to whether he taught that man descended from a lower order of animals, and we cannot contradict that testimony, there is no logical thing to come except that the jury find a verdict that we may carry to the higher court, purely as a matter of proper procedure. We do not think it is fair to the court or counsel on the other side to waste a lot of time when we know this is the inevitable result and probably the best result for the case.
After they were brought in, Darrow then addressed the jury:
We came down here to offer evidence in this case and the court has held under the law that the evidence we had is not admissible, so all we can do is to take an exception and carry it to a higher court to see whether the evidence is admissible or not ... we cannot even explain to you that we think you should return a verdict of not guilty. We do not see how you could. We do not ask it.
Darrow closed the case for the defense without a final summation. Under Tennessee law, when the defense waived its right to make a closing speech, the prosecution was also barred from summing up its case, preventing Bryan from presenting his prepared summation.
Scopes never testified since there was never a factual issue as to whether he had taught evolution. Scopes later admitted that, in reality, he was unsure of whether he had taught evolution (another reason the defense did not want him to testify), but the point was not contested at the trial.
William Jennings Bryan's summation of the Scopes trial, which was distributed to reporters but not read in court, read:
Science is a magnificent force, but it is not a teacher of morals. It can perfect machinery, but it adds no moral restraints to protect society from the misuse of the machine. It can also build gigantic intellectual ships, but it constructs no moral rudders for the control of storm-tossed human vessel. It not only fails to supply the spiritual element needed but some of its unproven hypotheses rob the ship of its compass and thus endanger its cargo. In war, science has proven itself an evil genius; it has made war more terrible than it ever was before. Man used to be content to slaughter his fellowmen on a single plane, the earth's surface. Science has taught him to go down into the water and shoot up from below and to go up into the clouds and shoot down from above, thus making the battlefield three times as bloody as it was before; but science does not teach brotherly love. Science has made war so hellish that civilization was about to commit suicide; and now we are told that newly discovered instruments of destruction will make the cruelties of the late war seem trivial in comparison with the cruelties of wars that may come in the future. If civilization is to be saved from the wreckage threatened by intelligence not consecrated by love, it must be saved by the moral code of the meek and lowly Nazarene. His teachings, and His teachings alone, can solve the problems that vex the heart and perplex the world.
After eight days of trial, it took the jury only nine minutes to deliberate. Scopes was found guilty on July 21 and ordered by Raulston to pay a $100 fine (equivalent to $1,800 in 2024). Raulston imposed the fine before Scopes was given an opportunity to say anything about why the court should not impose punishment upon him and after Neal brought the error to the judge's attention the defendant spoke for the first and only time in court:
Your honor, I feel that I have been convicted of violating an unjust statute. I will continue in the future, as I have in the past, to oppose this law in any way I can. Any other action would be in violation of my ideal of academic freedom—that is, to teach the truth as guaranteed in our constitution, of personal and religious freedom. I think the fine is unjust.
Bryan died suddenly five days after the trial's conclusion. The connection between the trial and his death is still debated by historians.
== Appeal to the Supreme Court of Tennessee ==
Scopes's lawyers appealed, challenging the conviction on several grounds. First, they argued that the statute was overly vague because it prohibited the teaching of "evolution", a very broad term. The court rejected that argument, holding:
Evolution, like prohibition, is a broad term. In recent bickering, however, evolution has been understood to mean the theory which holds that man has developed from some pre-existing lower type. This is the popular significance of evolution, just as the popular significance of prohibition is prohibition of the traffic in intoxicating liquors. It was in that sense that evolution was used in this act. It is in this sense that the word will be used in this opinion, unless the context otherwise indicates. It is only to the theory of the evolution of man from a lower type that the act before us was intended to apply, and much of the discussion we have heard is beside this case.
Second, the lawyers argued that the statute violated Scopes' constitutional right to free speech because it prohibited him from teaching evolution. The court rejected this argument, holding that the state was permitted to regulate his speech as an employee of the state:
He was an employee of the state of Tennessee or of a municipal agency of the state. He was under contract with the state to work in an institution of the state. He had no right or privilege to serve the state except upon such terms as the state prescribed. His liberty, his privilege, his immunity to teach and proclaim the theory of evolution, elsewhere than in the service of the state, was in no wise touched by this law.
Third, it was argued that the terms of the Butler Act violated the Tennessee State Constitution, which provided that "It shall be the duty of the General Assembly in all future periods of this government, to cherish literature and science." The argument was that the theory of the descent of man from a lower order of animals was now established by the preponderance of scientific thought, and that the prohibition of the teaching of such theory was a violation of the legislative duty to cherish science. The court rejected this argument, holding that the determination of what laws cherished science was an issue for the legislature, not the judiciary:
The courts cannot sit in judgment on such acts of the Legislature or its agents and determine whether or not the omission or addition of a particular course of study tends to cherish science.
Fourth, the defense lawyers argued that the statute violated the provisions of the Tennessee Constitution that prohibited the establishment of a state religion. The Religious Preference provisions of the Tennessee Constitution (Section 3 of Article I) stated, "no preference shall ever be given, by law, to any religious establishment or mode of worship".
Writing for the court two sittings and one year after receiving the appeal, Chief Justice Grafton Green rejected this argument, holding that the Tennessee Religious Preference clause was designed to prevent the establishment of a state religion as had been the experience in England and Scotland at the writing of the Constitution, and held:
We are not able to see how the prohibition of teaching the theory that man has descended from a lower order of animals gives preference to any religious establishment or mode of worship. So far as we know, there is no religious establishment or organized body that has in its creed or confession of faith any article denying or affirming such a theory. So far as we know, the denial or affirmation of such a theory does not enter into any recognized mode of worship. Since this cause has been pending in this court, we have been favored, in addition to briefs of counsel and various amici curiae, with a multitude of resolutions, addresses, and communications from scientific bodies, religious factions, and individuals giving us the benefit of their views upon the theory of evolution. Examination of these contributions indicates that Protestants, Catholics, and Jews are divided among themselves in their beliefs, and that there is no unanimity among the members of any religious establishment as to this subject. Belief or unbelief in the theory of evolution is no more a characteristic of any religious establishment or mode of worship than is belief or unbelief in the wisdom of the prohibition laws. It would appear that members of the same churches quite generally disagree as to these things.
Further, the court held that while the statute forbade the teaching of evolution (as the court had defined it) it did not require teaching any other doctrine and thus did not benefit any one religious doctrine or sect over others.
Nevertheless, having found the statute to be constitutional, the court set aside the conviction on appeal because of a legal technicality: the jury should have decided the fine, not the judge, since under the state constitution, Tennessee judges could not at that time set fines above $50, and the Butler Act specified a minimum fine of $100.
Justice Green added a totally unexpected recommendation:
The court is informed that the plaintiff in error is no longer in the service of the state. We see nothing to be gained by prolonging the life of this bizarre case. On the contrary, we think that the peace and dignity of the state, which all criminal prosecutions are brought to redress, will be the better conserved by the entry of a nolle prosequi herein. Such a course is suggested to the Attorney General.
Attorney General L. D. Smith immediately announced that he would not seek a retrial, while Scopes' lawyers offered angry comments on the stunning decision.
In 1968, the Supreme Court of the United States ruled in Epperson v. Arkansas 393 U.S. 97 (1968) that such bans contravene the Establishment Clause of the First Amendment because their primary purpose is religious. Tennessee had repealed the Butler Act the previous year.
== Aftermath and legacy ==
=== Creation versus evolution debate ===
The trial revealed a growing chasm in American Christianity and two ways of finding truth, one "biblical" and one "evolutionist". Author David Goetz writes that the majority of Christians denounced evolution at the time.
Author Mark Edwards contests the conventional view that in the wake of the Scopes trial, a humiliated fundamentalism retreated into the political and cultural background, a viewpoint which is evidenced in the 1955 play Inherit the Wind (and subsequent 1960 film), which fictionalized the trial, as well as in the majority of contemporary historical accounts. Rather, the cause of fundamentalism's retreat was the death of its leader, Bryan. Most fundamentalists saw the trial as a victory rather than a defeat, but Bryan's death soon after it created a leadership void that no other fundamentalist leader could fill. Bryan, unlike the other leaders, brought name recognition, respectability, and the ability to forge a broad-based coalition of fundamentalist and mainline religious groups which argued in defense of the anti-evolutionist position.
Adam Shapiro criticized the view that the Scopes trial was an essential and inevitable conflict between religion and science, claiming that such a view was "self-justifying". Instead, Shapiro emphasizes the fact that the Scopes trial was the result of particular circumstances, such as politics postponing the adoption of new textbooks.
=== Anti-evolution movement ===
The trial escalated the political and legal conflict in which strict creationists and scientists struggled over the teaching of evolution in Arizona and California science classes. Before the Dayton trial only the South Carolina, Oklahoma, and Kentucky legislatures had dealt with anti-evolution laws or riders to educational appropriations bills. After Scopes was convicted, creationists throughout the United States sought similar anti-evolution laws for their states.
By 1927, there were 13 states, both in the North and in the South, that had deliberated over some form of anti-evolution law. At least 41 bills or resolutions were introduced into the state legislatures, with some states facing the issue repeatedly. Nearly all these efforts were rejected, but Mississippi and Arkansas did put anti-evolution laws on the books after the Scopes trial, laws that would outlive the Butler Act, which was repealed in 1967. In 1968, the United States Supreme Court ruled in Epperson v. Arkansas that laws prohibiting the teaching of evolution violated the Establishment Clause of the First Amendment.
In the Southwest, anti-evolution crusaders included ministers R. S. Beal and Aubrey L. Moore in Arizona and members of the Creation Research Society in California. They sought to ban evolution as a topic for study in the schools or, failing that, to relegate it to the status of unproven hypothesis perhaps taught alongside the biblical version of creation. Educators, scientists, and other distinguished laymen favored evolution. This struggle occurred later in the Southwest than elsewhere, finally collapsing in the Sputnik era after 1957, when the national mood inspired increased trust for science in general and for evolution in particular.
The opponents of evolution made a transition from the anti-evolution crusade of the 1920s to the creation science movement of the 1960s. Despite some similarities between these two causes, the creation science movement represented a shift from overtly religious to covertly religious objections to evolutionary theory—sometimes described as a Wedge Strategy—raising what it claimed was scientific evidence in support of a literal interpretation of the Bible. Creation science also differed in terms of popular leadership, rhetorical tone, and sectional focus. It lacked a prestigious leader like Bryan, utilized pseudoscientific rather than religious rhetoric, and was a product of California and Michigan instead of the South.
=== Teaching of science ===
The Scopes trial had both short- and long-term effects in the teaching of science in schools in the United States. Though often portrayed as influencing public opinion against fundamentalism, the victory was not complete. Though the ACLU had taken on the trial as a cause, in the wake of Scopes' conviction they were unable to find more volunteers to take on the Butler law and, by 1932, had given up. The anti-evolutionary legislation was not challenged again until 1965, and in the meantime, William Jennings Bryan's cause was taken up by a number of organizations, including the Bryan Bible League and the Defenders of the Christian Faith.
The effects of the Scopes Trial on high school biology texts has not been unanimously agreed by scholars. Of the most widely used textbooks after the trial, only one included the word evolution in its index; the relevant page includes biblical quotations. Some scholars have accepted that this was the result of the Scopes Trial: for example Hunter, the author of the biology text which Scopes was on trial for teaching, revised the text by 1926 in response to the Scopes Trial controversy. However, George Gaylord Simpson challenged this notion as confusing cause and effect, and instead posited that the trend of anti-evolution movements and laws that provoked the Scopes Trial was also to blame for the removal of evolution from biological texts, and that the trial itself had little effect. The fundamentalists' target slowly veered off evolution in the mid-1930s. Miller and Grabiner suggest that as the anti-evolutionist movement died out, biology textbooks began to include the previously removed evolutionary theory. This also corresponds to the emerging demand that science textbooks be written by scientists rather than educators or education specialists.
This account of history has also been challenged. In Trying Biology Robert Shapiro examines many of the eminent biology textbooks in the 1910–1920s, and finds that while they may have avoided the word evolution to placate anti-evolutionists, the overall focus on the subject was not greatly diminished, and the books were still implicitly evolution based. It has also been suggested that the narrative of evolution's being removed from textbooks due to religious pressure, only to be reinstated decades later, was an example of "Whig history" propagated by the Biological Sciences Curriculum Study, and that the shift in the ways biology textbooks discussed evolution can be attributed to other race and class based factors.
In 1958 the National Defense Education Act was passed with the encouragement of many legislators who feared the United States education system was falling behind that of the Soviet Union. The act yielded textbooks, produced in cooperation with the American Institute of Biological Sciences, which stressed the importance of evolution as the unifying principle of biology. The new educational regime was not unchallenged. The greatest backlash was in Texas where attacks were launched in sermons and in the press. Complaints were lodged with the State Textbook Commission. However, in addition to federal support, a number of social trends had turned public discussion in favor of evolution. These included increased interest in improving public education, legal precedents separating religion and public education, and continued urbanization in the South. This led to a weakening of the backlash in Texas, as well as to the repeal of the Butler Law in Tennessee in 1967.
=== Other implications ===
Historian Randall Balmer argues that the Scopes trial and Bryan's death resulted in a decline in the influence of Christian fundamentalists in American politics. While a subculture of evangelical organizations developed over the succeeding decades, conservative Protestants were not mobilized into a distinct voting bloc and were in effect politically inactive. It was not until the rise of the Christian right in the late 1970s that conservative fundamentalists became politically active and powerful again.
=== Commemoration ===
Bryan College is a private Christian college in Dayton that was established in 1930 in honor of William Jennings Bryan. Bryan had long expressed a desire for the establishment of a fundamentalist Biblical higher educational institution, and during the trial suggested that such a school be established in Dayton.
The Rhea County Courthouse was listed on the National Register of Historic Places in 1972 and was designated a National Historic Landmark by the National Park Service in 1976 for its role in the trial. Between 1977 and 1979 a rehabilitation project was undertaken on the 1891-built courthouse, which had fallen into disrepair. This included restoring the second-floor courtroom to its appearance during the Scopes trial and the establishment of the Rhea County Heritage and Scopes Trial Museum, which opened on May 11, 1979. Located in the basement of the courthouse, this museum contains such memorabilia as the microphone used to broadcast the trial, trial records, photographs, and an audiovisual history.
Since 1988, locals have participated in a play called "Destiny in Dayton", a re-enactment of key moments of the trial in that takes place in the courtroom during July. This evolved into the larger Scopes Trial Festival in 1989, which includes vendors, craftsmen, and live music. The Tennessee Historical Commission erected a historical marker in front of the courthouse which commemorates the site of the trial. In 2005, a statue of William Jennings Bryan was dedicated on the courthouse lawn, funded by a donation from nearby Bryan College. In 2017, a statue of Clarence Darrow was unveiled near Bryan's statue, funded by a donation from the Freedom From Religion Foundation.
== Media coverage and publicity ==
The Scopes trial was covered by journalists from the South and around the world, including H. L. Mencken for The Baltimore Sun, which was also paying part of the defense's expenses. It was Mencken who provided the trial with its most colorful labels such as the "Monkey Trial" of "the infidel Scopes". It was also the first United States trial to be broadcast on national radio. Edward J. Larson, a historian who won the Pulitzer Prize for History for his book Summer for the Gods: The Scopes Trial and America's Continuing Debate Over Science and Religion (2004), notes: "Like so many archetypal American events, the trial itself began as a publicity stunt." The press coverage of the "Monkey Trial" was overwhelming. The trial served its intention to bring publicity to the town of Dayton. From The Salem Republican, June 11, 1925:
The whole matter has assumed the portion of Dayton and her merchants endeavoring to secure a large amount of notoriety and publicity with an open question as to whether Scopes is a party to the plot or not.
The front pages of major newspapers including The New York Times were dominated by the case for days. More than 200 newspaper reporters from all parts of the country and two from London were in Dayton. Twenty-two telegraphers sent out 165,000 words per day on the trial, over thousands of miles of telegraph wires hung for the purpose; more words were transmitted to Britain about the Scopes trial than for any previous American event. Trained chimpanzees performed on the courthouse lawn. Chicago's WGN radio station broadcast the trial with announcer Quin Ryan via clear-channel broadcasting first on-the-scene coverage of the criminal trial. Two movie cameramen had their film flown out daily in a small plane from a specially prepared airstrip. The event became known as the "Trial of the Century", and has been described as the most-covered trial in American history, with only the murder trial of O. J. Simpson some 70 years later receiving comparable coverage.
H.L. Mencken's trial reports were vituperative and heavily slanted against the prosecution and the jury, which he described as "unanimously hot for Genesis". He mocked the town's inhabitants as "Babbits", "yokels", "morons", "peasants", "hill-billies", and "yaps", and called Bryan a "buffoon" and his speeches "theologic bilge". He chastised the "degraded nonsense which country preachers are ramming and hammering into yokel skulls". In contrast, he called the defense "eloquent" and "magnificent". Even today, some American creationists, fighting in courts and state legislatures to demand that creationism be taught on an equal footing with evolution in the schools, have claimed that it was Mencken's trial reports in 1925 that turned public opinion against creationism. The media's portrayal of Darrow's cross-examination of Bryan, and the play and movie Inherit the Wind (1960), have been credited with causing millions of Americans to ridicule religious-based opposition to the theory of evolution.
Mencken, however, did enjoy certain aspects of Dayton, writing
The town, I confess, greatly surprised me. I expected to find a squalid Southern village, with darkies snoozing on the horse-blocks, pigs rooting under the houses and the inhabitants full of hookworm and malaria. What I found was a country town full of charm and even beauty—a somewhat smallish but nevertheless very attractive Westminster or Balair.
Mencken described Rhea County as priding itself on a kind of tolerance or what he called "lack of Christian heat", opposed to outside ideas but without hating those who held them. He pointed out that the Ku Klux Klan did not have a foothold locally, despite is power throughout much of the state. Mencken attempted to perpetrate a hoax, distributing flyers for the "Rev. Elmer Chubb", but the claims that Chubb would drink poison and preach in lost languages were ignored as commonplace by the people of Dayton, and only Commonweal magazine bit. Mencken continued to attack Bryan, including in his withering obituary of Bryan, "In Memoriam: W.J.B.", in which he charged Bryan with "insincerity"—not for his religious beliefs but for the inconsistent and contradictory positions he took on a number of political questions during his career. Years later, Mencken did question whether dismissing Bryan "as a quack pure and unadulterated" was "really just". Mencken's columns made the Dayton citizens irate and drew general indignation from the Southern press. After Raulston ruled against the admission of scientific testimony, Mencken left Dayton, declaring in his last dispatch "All that remains of the great cause of the State of Tennessee against the infidel Scopes is the formal business of bumping off the defendant." Consequently, the journalist missed Darrow's cross-examination of Bryan on Monday.
Anticipating that Scopes would be found guilty, the press fitted the defendant for martyrdom and created an onslaught of ridicule, and hosts of cartoonists added their own portrayals to the attack. Time magazine's initial coverage of the trial focused on Dayton as "the fantastic cross between a circus and a holy war". Life magazine adorned its masthead with monkeys reading books and proclaimed "the whole matter is something to laugh about." Both Literary Digest and the popular humor magazine Life (1890–1930) ran compilations of jokes and humorous observations garnered from newspapers around the country. American Experience has published a gallery of such cartoons written about the trial, and 14 such cartoons are also reprinted in L. Sprague de Camp's The Great Monkey Trial.
Overwhelmingly, the butt of these jokes was the prosecution and those aligned with it: Bryan, the city of Dayton, the state of Tennessee, and the entire South, as well as fundamentalist Christians and anti-evolutionists. Rare exceptions were found in the Southern press, where the fact that Darrow had saved Leopold and Loeb from the death penalty continued to be a source of ugly humor. The most widespread form of this ridicule was directed at the inhabitants of Tennessee. Life described Tennessee as "not up to date in its attitude to such things as evolution". Attacks on Bryan were also frequent and acidic. Life awarded him its "Brass Medal of the Fourth Class" for having "successfully demonstrated by the alchemy of ignorance hot air may be transmuted into gold, and that the Bible is infallibly inspired except where it differs with him on the question of wine, women, and wealth". Time magazine related Bryan's arrival in town with the disparaging comment "The populace, Bryan's to a moron, yowled a welcome."
== In popular culture ==
=== Stage, film and television ===
Jerome Lawrence and Robert Edwin Lee's play Inherit the Wind (1955), fictionalizes the 1925 Scopes "Monkey" Trial as a means to discuss the then-contemporary McCarthy trials. It portrays Darrow and Bryan as the characters who are named Henry Drummond and Matthew Brady. In a note at the opening of the play, the playwrights state that it is not meant to be a historical account, and there are numerous instances where events were substantially altered or invented. Despite the disclaimer in the play's preface that the trial was its "genesis" but it is "not history", the play has largely been accepted as history by the public. (Lawrence and Lee later said that it was written in response to McCarthyism and was chiefly about intellectual freedom.)
Adaptations:
Inherit the Wind was made into a 1960 film directed by Stanley Kramer, with Spencer Tracy as Drummond and Fredric March as Brady. Although there are numerous changes in the plot, they include more of the actual events which are recorded in the trial transcript, such as when Darrow implies that the court is prejudiced, being cited for contempt of court for his comments and his subsequent statement of contrition that persuaded the judge to drop the charge.
There have also been three television versions of the play, with Melvyn Douglas and Ed Begley in 1965, Jason Robards and Kirk Douglas in 1988, and Jack Lemmon and George C. Scott in 1999.
Peter Goodchild's play, The Great Tennessee Monkey Trial (1993), was based on original sources and transcripts of the Scopes trial, because it was written with the goal of being historically accurate. It was produced as part of L.A. Theatre Works' Relativity Series, which features science-themed plays and receives major funding from the Alfred P. Sloan Foundation, which seeks "to enhance public understanding of science and technology in the modern world". According to Audiofile Magazine, which pronounced this production the 2006 D.J.S. Winner of AudioFile Earphones Award: "Because there are no recordings of the actual trial, this production is certainly the next best thing." The BBC broadcast The Great Tennessee Monkey Trial in 2009, in a radio version starring Neil Patrick Harris and Ed Asner.
Gale Johnson's play Inherit the Truth (1987) was based on the original transcripts of the case. Inherit the Truth was performed yearly during the Dayton Scopes Festival until it ended its run in 2009. The play was written as a rebuttal of the 1955 play and the 1960 film, which Dayton residents claim did not accurately depict either the trial or William Jennings Bryan. In 2007 Bryan College purchased the rights to the production and began work on a student film version of the play, which was screened at that year's Scopes Festival.
The 1997 The Simpsons episode "Lisa the Skeptic" drew inspiration from the trial, along with the Cardiff Giant and Piltdown Man hoaxes.
The film Alleged (2010), a romantic drama which is set around the Scopes Trial, starring Brian Dennehy as Clarence Darrow and Fred Thompson as William Jennings Bryan, was released by Two Shoes Productions. While the main storyline is fictional, all the courtroom scenes are accurate according to the actual trial transcripts. Coincidentally, Dennehy had played Matthew Harrison Brady, the fictionalized counterpart of Bryan, in the 2007 Broadway revival of Inherit the Wind.
In 2013, the Comedy Central series Drunk History retold portions of the trial in the "Nashville" episode, with Bradley Whitford portraying Bryan, Jack McBrayer as Darrow, and Derek Waters as Scopes.
=== Art ===
Gallery: Monkey Trial shows cartoons made in reaction to the trial.
=== Literature ===
Ronald Kidd's 2006 novel, Monkey Town: The Summer of the Scopes Trial, set in summer 1925, in Dayton, Tennessee, is based on the Scopes Trial.
=== Music ===
A series of folk songs produced in reaction to the trial, from PBS' American Experience, includes:
"Bryan's Last Fight"
"Can't Make a Monkey of Me"
"Monkey Business"
"Monkey Out of Me"
"The John Scopes Trial (The Old Religion's Better After All)"
"There Ain't No Bugs"
"Monkey Biz-Ness (Down in Tennessee)" by the International Novelty Orchestra with Billy Murray is a 1925 comedy song about the Scopes Monkey Trial.
Bruce Springsteen performed a song called "Part Man, Part Monkey" during his 1988 Tunnel of Love Express Tour, and recorded a version of it in 1990 that was first released as a 1992 B-side and was later released on the 1998 multi-volume Tracks collection. The song references the Scopes trial ("They prosecuted some poor sucker in these United States / For teaching that man descended from the apes") but says that the trial could have been avoided by merely looking at how men behave around women ("They coulda settled that case without a fuss or fight / If they'd seen me chasing you, sugar, through the jungle last night / They'da called in that jury and a one two three, said / Part man, part monkey, definitely").
=== Non-fiction ===
It was not until the 1960s that the Scopes trial began to be mentioned in the history textbooks which were used in American high schools and colleges. Such textbooks usually portrayed it as an example of the conflict between fundamentalists and modernists, and it was frequently mentioned in the sections of those same textbooks which also described the rise of the second iteration of the Ku Klux Klan in the South, which occurred around the same time.
== See also ==
== Notes ==
== References ==
=== Citations ===
=== Bibliography ===
de Camp, L. Sprague (1968), The Great Monkey Trial, Doubleday, ISBN 978-0-385-04625-1
Clark, Constance Areson (2000), "Evolution for John Doe: Pictures, The Public, and the Scopes Trial Debate", Journal of American History, 87 (4): 1275–1303, doi:10.2307/2674729, ISSN 0021-8723, JSTOR 2674729, PMID 17120375
Conkin, Paul K. (1998), When All the Gods Trembled: Darwinism, Scopes, and American Intellectuals, Rowman & Littlefield Publishers, p. 185, ISBN 978-0-8476-9063-3
Edwards, Mark (2000), "Rethinking the Failure of Fundamentalist Political Antievolutionism after 1925", Fides et Historia, 32 (2): 89–106, ISSN 0884-5379, PMID 17120377
Folsom, Burton W. Jr. (1988), "The Scopes Trial Reconsidered", Continuity (12): 103–127, ISSN 0277-1446
Gatewood, Willard B. Jr., ed. (1969), Controversy in the Twenties: Fundamentalism, Modernism, & Evolution
Harding, Susan (1991), "Representing Fundamentalism: The Problem of the Repugnant Cultural Other", Social Research, 58 (2): 373–393
Grabiner, J. V. & Miller, P. D. (September 6, 1974) "Effects of the Scopes Trial", Science, New Series, Vol. 185, No. 4154, pp. 832–837
Ladouceur, Ronald P. (2008) "Ella Thea Smith and the Lost History of American High School Biology Textbooks", Journal of the History of Biology, Vol. 41, No. 3, pp. 435–471
Larson, Edward J. (1997), Summer for the Gods: The Scopes Trial and America's Continuing Debate Over Science and Religion, BasicBooks, ISBN 978-0-465-07509-6
Larson, Edward J. (2004), Evolution, Modern Library, ISBN 978-0-679-64288-6
Lienesch, Michael (2007), In the Beginning: Fundamentalism, the Scopes Trial, and the Making of the Antievolution Movement, University of North Carolina Press, pp. 350pp, ISBN 978-0-8078-3096-3
Menefee, Samuel Pyeatt (2001), "Reaping the Whirlwind: A Scopes Trial Bibliography", Regent University Law Review, 13 (2): 571–595
Moran, Jeffrey P. (2002), The Scopes Trial: A Brief History with Documents, Bedford/St. Martin's, pp. 240pp, ISBN 978-0-312-24919-9
Moran, Jeffrey P. (2004), "The Scopes Trial and Southern Fundamentalism in Black and White: Race, Region, and Religion", Journal of Southern History, 70 (1): 95–120, doi:10.2307/27648313, JSTOR 27648313, archived from the original on May 4, 2012, retrieved September 11, 2017
Shapiro, Adam R. Trying Biology: The Scopes Trial, Textbooks, and the Antievolution Movement in American Schools (2013) excerpt and text search
Smout, Kary Doyle (1998), The Creation/Evolution Controversy: A Battle for Cultural Power, Bloomsbury Academic, pp. 210 pp, ISBN 978-0-275-96262-3
Scopes, John T.; Presley, James (June 1967), Center of the Storm: Memoirs of John T. Scopes, Henry Holt & Company, ISBN 978-0-03-060340-2
Simpson, George Gaylord (February 7, 1975) "Evolution and Education", Science Vol. 187, Issue 4175, pp. 389
Tompkins, Jerry R. (1968), D-Days at Dayton: Reflections on the Scopes Trial, Louisiana State University Press, OCLC 411836
== Further reading ==
Cline, Austin. "Atheism: Scopes Monkey Trial". About.com. Archived from the original on December 25, 2018. Retrieved April 15, 2007.
Ginger, Ray. Six Days or Forever?: Tennessee v. John Thomas Scopes. London: OUP, 1974 [1958].
Haldeman-Julius, Marcet. "Impressions of the Scopes Trial". Haldeman-Julius Monthly, vol. 2.4 (Sept. 1925), pp. 323–347 (excerpt—included in Clarence Darrow's Two Great Trials (1927). Haldeman-Julius was an eye-witness and a friend of Darrow's.]
McKay, Casey Scott (2013). "Tactics, Strategies, & Battles—Oh My!: Perseverance of the Perpetual Problem Pertaining to Preaching to Public School Pupils & Why it Persists". University of Massachusetts Law Review. 8 (2): 442–464. Article 3.
Mencken, H.L. A Religious Orgy in Tennessee: A Reporter's Account of the Scopes Monkey Trial. Hoboken: Melville House, 2006.
"Monkey Trial". American Experience. PBS.
Scopes, John Thomas and William Jennings Bryan. The World's Most Famous Court Trial: Tennessee Evolution Case: A Complete Stenographic Report of the Famous Court Test. Cincinnati: National Book Co., ca. 1925.
Shapiro, Adam R. Trying Biology: The Scopes Trial, Textbooks, and the Antievolution Movement in American Schools. Chicago: UCP, 2013.
Shapiro, Adam R. "'Scopes Wasn't the First': Nebraska's 1924 Anti-Evolution Trial". Nebraska History, vol. 94 (Fall 2013), pp. 110–119.
The Church Case between Prof. Johannes du Plessis and the Dutch Reformed Church in Cape Town, South Africa, on February 27, 1930 – 1931, regarding the biblical chapter of Genesis and evolution, was a similar event. The Church lost its case. OCLC 85987149
Wineapple, Brenda. Keeping the Faith: God, Democracy, and the Trial That Riveted a Nation. New York: Random House, 2024.
== External links ==
Original materials from and news coverage of the trial:
Complete trial transcripts and other court documents at University of Minnesota Law Library
The World's Most Famous Court Trial on the website of Professor Joe Cain from UCL
Mencken's complete columns on the Scopes Trial at the Internet Archive
Papers of Warner B. Ragsdale, a reporter covering the trial in University of Maryland Library
Readings (audio) of H.L. Mencken's reports of the trial from The Baltimore Evening Sun Archived December 22, 2017, at the Wayback Machine
Scopes Trial Home Page by Douglas Linder. University of Missouri at Kansas City Law School
Bryan, William Jennings (1925). "Text of the Closing Statement of William Jennings Bryan at the trial of John Scopes". California State University Dominguez Hills. Dayton, Tennessee. Archived from the original on July 13, 2017. Retrieved July 14, 2006.
Marks, Jonathan. "Transcript of Bryan's cross-examination". University of North Carolina. Charlotte, NC. Archived from the original on June 14, 2007.
"Unpublished Photographs from 1925 Tennessee vs. John Scopes "Monkey Trial"". Smithsonian Archives.
Human Timeline (Interactive) – Smithsonian, National Museum of Natural History (August 2016).
Scopes Trial, digital collection, Tennessee Virtual Archive. | Wikipedia/Scopes_Trial |
The Blackwell Companion to Science and Christianity is a reference work in science and religion, edited by James B. Stump and Alan G. Padgett, and published by Wiley-Blackwell in 2012. It contains 54 new essays written by an international list of 55 authors, many of them leading scholars in the discipline of science and religion, and others new or up-and-coming voices in the field. The editors claim, "We are seeking to introduce and advance serious thinking and talking about science and Christianity, particularly as they interconnect. We are reflecting on the work of scientists and theologians, trying to find points of contact and points of tension which help to illuminate these practices and doctrines in clear, scholarly light." The book has received positive reviews in Choice, Reference Reviews, Themelios and Perspectives on Science and Christian Faith. The article by Sean M. Carroll generated significant attention when it was discussed on the Huffington Post.
== Contents ==
Part I - Historical Episodes
Part II - Methodology
Part III - Natural Theology
Part IV - Cosmology and Physics
Part V - Evolution
Part VI - The Human Sciences
Part VII - Christian Bioethics
Part VIII - Metaphysical Implications
Part IX - The Mind
Part X - Theology
Part XI - Significant Figures of the Twentieth Century in Science and Christianity
== References ==
== External links ==
The Blackwell Companion to Science and Christianity on the Wiley website
Google Books page
WorldCat entry | Wikipedia/The_Blackwell_Companion_to_Science_and_Christianity |
The relationship between Buddhism and science is a subject of contemporary discussion and debate among Buddhists, scientists, and scholars of Buddhism. Historically, Buddhism encompasses many types of beliefs, traditions and practices, so it is difficult to assert any single "Buddhism" in relation to science. Similarly, the issue of what "science" refers to remains a subject of debate, and there is no single view on this issue. Those who compare science with Buddhism may use "science" to refer to "a method of sober and rational investigation" or may refer to specific scientific theories, methods or technologies.
There are many examples throughout Buddhism of beliefs such as dogmatism, fundamentalism, clericalism, and devotion to supernatural spirits and deities. Nevertheless, since the 19th century, numerous modern figures have argued that Buddhism is rational and uniquely compatible with science. Some have even argued that Buddhism is "scientific" (a kind of "science of the mind" or an "inner science"). Those who argue that Buddhism is aligned with science point out certain commonalities between the scientific method and Buddhist thought. The 14th Dalai Lama, for example, in a speech to the Society for Neuroscience, listed a "suspicion of absolutes" and a reliance on causality and empiricism as common philosophical principles shared by Buddhism and science.
Buddhists also point to various statements in the Buddhist scriptures that promote rational and empirical investigation and invite people to put the teachings of the Buddha to the test before accepting them. Furthermore, Buddhist doctrines such as impermanence and emptiness have been compared to the scientific understanding of the natural world. However, some scholars have criticized the idea that Buddhism is uniquely rational and science friendly, seeing these ideas as a minor element of traditional Buddhism. Scholars like Donald Lopez Jr. have also argued that this narrative of Buddhism as rationalistic developed recently, as a part of a Buddhist modernism that arose from the encounter between Buddhism and western thought.
Furthermore, while some have compared Buddhist ideas to modern theories of evolution, quantum theory, and cosmology, other figures such as the 14th Dalai Lama have also highlighted the methodological and metaphysical differences between these traditions. For the Dalai Lama, Buddhism mainly focuses on studying consciousness from the first-person or phenomenological perspective, while science focuses on studying the objective world.
== Pre-modern Buddhism ==
=== Rational inquiry in Buddhist texts ===
Some modern commentators assert that Buddhist texts contain ideas which share commonalities with modern scientific methods, such as encouraging an impartial investigation of nature (an activity referred to as dhamma-vicaya in the Pali Canon) — the principal object of study being the nature of one's mind or self.
Several passages from the Buddhist scriptures have been seen as indicating the importance of free thinking and empirical inquiry to Buddhism. Perhaps the most popular Buddhist discourse used in this way is the Kālāma Sutta (AN 3.65). In this discourse, the Buddha is speaking to a number of villagers that are unsure of which ideas to believe. The key passage which is widely quoted states:Come, Kālāmas, do not go by oral tradition, by lineage of teaching, by hearsay, by a collection of scriptures, by logical reasoning, by inferential reasoning, by reasoned cogitation, by the acceptance of a view after pondering it, by the seeming competence of a speaker, or because you think: 'The ascetic is our guru.' But when, Kālāmas, you know for yourselves: 'These things are unwholesome; these things are blameworthy; these things are censured by the wise; these things, if accepted and undertaken, lead to harm and suffering,' then you should abandon them.The exact meaning of this passage has been widely debated and interpreted. Buddhist modernists consider this passage to show that the Buddha promoted a skeptical empirical investigation which rejected faith, dogma, scripture, Revelations and even rationalistic metaphysical speculations. Buddhist philosophers like K.N. Jayatilleke argue that this and other passages from the Buddhist scriptures indicate that early Buddhism promotes an "honest, impartial search for truth" as well as "critical investigation and personal verification" which is compatible with a scientific outlook. However, Bhikkhu Bodhi notes that this sutra does not rule out faith as an important component of the path. Another discourse, the Vīmaṃsaka Sutta (MN 47, with a Chinese parallel at MA 186) has been called "a remarkable advocacy of free inquiry" by Bhikkhu Analayo.
=== Reason and logic in Buddhist scholasticism ===
Buddhist texts contain exhortations to examine the teachings of the Buddha through reason and experience. Śāntarakṣita's (725–788 CE) Tattvasaṃgraha cites a well known scriptural passage that is also cited by the 14th Dalai Lama and other Buddhists:"O monks, like gold that is heated, cut, and rubbed, my words should be analyzed by the wise and then accepted; they should not do so out of reverence." – A Sutra on Pure Realms Spread Out in a Dense Array
Buddhism also has a long tradition of epistemology and logic. Buddhist philosophers in this tradition, such as Dignāga and Dharmakīrti, developed complex theories of knowledge which held that there were only two "instruments of knowledge" or "epistemic tools" (pramana): perception and inference.
According to Cristian Coseru, Dignāga's theory of knowledge is strongly grounded on perception. Furthermore, unlike other Indian theories of knowledge, Indian Buddhist philosophers like Dharmakīrti (fl. c. 6th or 7th century) generally rejected scripture as a major epistemic instrument. Dharmakīrti held that one should not rely on scripture to decide issues that can be discovered through rational means and that one could reject unreasonable parts of scripture. However, he did argue that when it came to "radically inaccessible things" (such as karma), one could turn to scripture (which was an uncertain and fallible source).
=== Natural philosophy and proto-scientific practices ===
The early Buddhist texts contain various ideas about the nature of the world and the universe. However, they also warn against certain speculative questions regarding about the universe. In various early discourses, the Buddha rejects certain questions about the world as "unfathomable" or "unexplainable" (Skt. avyākṛta). These include questions about the eternity and the infinity of the universe. In the Cūḷamālukya Sutta, the Buddha uses the parable of a poisoned arrow to explain his approach to these questions, his teaching is focused on how to remove the arrow of suffering, not on the particular details about the arrow and who shot the arrow (and so forth). As Paul David Numrich writes, there are thus certain questions about the world that the Buddha sees as "irrelevant to the ultimate religious goal of liberation from the human condition."
In spite of this warning found in the Buddhist texts, Indian Buddhists developed complex theories about the physical world, including atomic theories, theories of sense perception, theories of time and space and Buddhist cosmology. Apart from teaching Buddhist philosophy, medieval Buddhist universities such as Nālandā (in modern day Bihar) were important centers for the study of natural philosophy and applied sciences such as cosmology, medicine and astronomy. Ancient Buddhist philosophy explored key questions about the natural world such as the nature of space and time, the nature and existence of atoms (and their indivisibility), the origin of the world and the relationship between mind and matter. It explored these questions through philosophical analysis and Thought experiments.
Medicine was a particularly important concern for ancient Buddhists, and references to it can be in all historical layers of Buddhist literature. Nālandā University was also said to have been the site of the composition of the Aṣṭāṅgahṛdaya-saṃhitā, an influential medical work by the physician Vāgbhaṭa. According to Pierce Salguero "Buddhist texts mentioning various aspects of medicine proliferated across the Buddhist world throughout the first millenium." Because of this, Buddhism was "one of the most important vehicles for the cross-cultural diffusion of Indian Medicine in pre-modern Asia." Closely related with this ancient medicine was the practice of Indian alchemy or rasaśāstra. Practitioners of rasaśāstra experimented with various substances and metals. Rasāyana is also an important part of some of the Buddhist tantras.
The Buddhist tradition of worldly sciences continued to develop in outside of India and today survives as part of Tibetan Medicine and Tibetan astrology (which includes astronomical and astrological elements). Traditional Buddhist cosmology taught that there were multiple world systems and that the universe goes through cycles of formation, endurance and destruction. It also holds that the universe has no absolute beginning (and thus rejects creationism and theism, but also the idea that the universe arose without a cause).
== Buddhism as scientific or as compatible with science ==
=== History of the Buddhist modernist discourse ===
==== 19th century modernism ====
A commonly held modern view is that Buddhism is exceptionally compatible with science and reason, or even that it is a kind of science (perhaps a "science of the mind" or a "scientific religion"). This view arose in the modern era, as part of what has been called "Buddhist modernism," and was defended by figures such as Migettuwatte Gunananda, Anagarika Dharmapala, Paul Carus, Shaku Sōen, D.T. Suzuki, Henry Olcott, and Edwin Arnold. These modernists accepted and promoted modern scientific theories such as evolution and held that they were consistent with the Buddhist understanding of Dharma (sometimes interpreted as a "natural law").
They also held that Buddhism was a rationalist religion that did not require faith in revelation, a God, superstition and religious ritual but was based on an understanding of causality and empiricism. According to Geoffrey Samuel, some of these modernists even "suggested that Buddhism was barely a religion at all in the Western sense, but a scientifically-based philosophy in its own right." Some of these figures also dismissed the "irrational" elements of Buddhism as folk superstition. According to Martin J. Verhoeven, Buddhist modernists downplay mythic and religious elements such as traditional Indic cosmology, belief in Miracles and rituals in favor of the rational and psychological aspects of Buddhism.
Paul Carus for example, wrote that Buddha was "the first positivist, the first humanitarian, the first radical freethinker," while D.T. Suzuki held that the Buddhist view of karma can be seen as "an application in our ethical realm of the theory of the conservation of energy". Similarly, both Anagarika Dharmapala's and Shaku Sōen's presentations at the World's Parliament of Religions in 1893 presented Buddhism as being founded on the law of cause and effect (associating scientific ideas of causality with the Buddhist doctrine of dependent origination). Carus and other Buddhist modernists saw Buddhism as having certain advantages over Christianity. They held that Buddhism accepted the scientific ideal of a universe ordered by natural laws and did not require belief in a God or any being that could alter natural laws. For many Asian Buddhists, the narrative of Buddhism as rational and scientific was a useful strategy used to counter Christian and colonial attacks on Buddhism as backward. Others like Shaku Sōen, sought to create a more rational westernized Buddhism, or as he put it, to "wed the Great Vehicle [Mahayana Buddhism] to Western thought."
The idea that the Buddhist worldview was rational and scientific is also seen in the popular Buddhist Catechism, written by Henry Olcott. This book contained a chapter on Buddhism and science that rejected miracles as an explanation for the Buddha's supposedly supernatural feats and instead offered natural explanations for them (such as hypnotism and theosophical occult science). This modernist view was also promoted by early Buddhist societies in the West, such as Karl Seidenstücker and George Grimm's Society for the Buddhist Mission in Leipzig and the British Buddhist Society. George Grimm's (1868–1945) The teaching of the Buddha, the Religion of Reason (Die Lehre des Buddho, die Religion der Vernunft) is an important exposition of this rationalistic Buddhism. According to McMahan, western commentators on this topic were responding to "the Victorian crisis of faith and the emergence of the immense symbolic capital of scientific discourse." José Ignacio Cabezón notes that there were different opinions among American Buddhist modernists during the late 19th century. Some were happy to note the similarities between science and Buddhism and believed Buddhism was more compatible with science than Christianity (which was more likely to die out due to scientific findings). Other Buddhist modernists like Carus saw Buddhism as the "Religion of Science," which would make scientific truth "the last guide of a religious conception of mankind."
==== 20th and 21st centuries ====
As noted by David McMahan, the modernist idea of Buddhism as being compatible with science continued into the 20th century and remains strong today, having become "not only more voluminous but far more sophisticated throughout the late twentieth century and is now at its productive and creative zenith." The Buddhist modernist view has also been expounded by a variety of western intellectuals, including Nobel Prize–winning philosopher Bertrand Russell, who described Buddhism as "a speculative and scientific philosophy."
In the late 20th century and the early 21st, numerous publications discussing Buddhist ideas and science were released (such as James H. Austin's Zen and the Brain and works by Francisco Varela and Daniel Goleman). Furthermore, according to McMahan "the compatibility of Buddhism and modern science has not only become a staple of popular Buddhist literature, it has also become a hypothesis in a large number of quite sophisticated experimental studies." The Mind and Life Institute is at the forefront of such studies. The Institute hosts conferences on Buddhism and science and sponsors research on Buddhist meditation. McMahan also argues that "perhaps no major tradition has attempted to adopt scientific discourse more vigorously than Buddhism." Geoffrey Samuel remarks that these dialogues point to the fact that westerners (including scientists) have come to take Buddhist ideas much more seriously as a valuable system of knowledge. The Mind and Life Institute has also influenced how Tibetan Buddhism is presented to western audiences, and it is also closely connected to the 14th Dalai Lama's promotion of scientific education among Tibetan Buddhist monks.
José Ignacio Cabezón argues that modern Buddhists have at times discussed the relationship between Buddhism and science in three main ways: conflict/ambivalence, identity/similarity, and complementarity. Cabezón outlines various kinds of views regarding complementarity. One of these ideas is that there is a "similarity in method, and difference in the object of study". This sees Buddhism as mainly a science of the subjective world, while science is mainly concerned with the external and material world. In this view, both disciplines can learn from each other regarding these fields. Another view "stresses difference in method and similarity in content." This view sees Buddhism as using "nonconceptual modes of intuitive understanding that emerge as the result of the practice of meditation" which is different from the objective and conceptual scientific method and leads to self transformation.
The discourse of complementarity often seeks to unify these different disciplines, which focus on different aspects (the exterior and interior worlds, the quantitative and the qualitative, reason and intuition, etc.). This discourse generally argues that there should be a balance and harmony between these elements. Cabezon singles out Fritjof Capra's The Tao of Physics as one of the most influential examples of the discourse of complementarity. According to Capra, none other than the great physicist Werner Heisenberg said that he was in "complete agreement" with the main idea of the book, mainly that the "two basic themes" found in modern physics ("the fundamental interrelatedness and interdependence of all phenomena and the intrinsically dynamic nature of reality") are also found in eastern thought.
The discourse of complementary can also be found in the work of Daniel Goleman, who writes regarding Buddhism and psychotherapy that "when you put the two psychologies together, you get a more complete spectrum of human development." Another publication which argues for the complementarity of science and Buddhist thought is The Embodied Mind (1991, Varela, Thompson & Rosch). This book argues that Buddhism can provide a sophisticated phenomenology of embodied experience.
=== Views of Theravada Buddhists ===
Since the Buddhist modernist revival in Southeast Asia, Theravada Buddhist intellectuals (such as Anagarika Dharmapala) have generally embraced science and have seen Buddhism as compatible with its findings.
For example, K.N. Jayatilleke (1920–1970), a Sinhalese Buddhist philosopher, writes that the Pali Canon, "emphasizes the importance of the scientific outlook in dealing with the problems of morality and religion. Its specific 'dogmas' are said to be capable of verification. And its general account of the nature of man and the universe is one that accords with the findings of science rather than being at variance with them." Jayatilleke points to the early Buddhist idea that there are many worlds, suns and "world systems" (lokadhatu) as an example. He also argues that the Buddhist idea that humans and nature are constantly changing according to causal laws is easily compatible with biological evolution and therefore, modern findings do not threaten the Buddhist worldview. Furthermore, Jayatilleke points out that Buddhism holds that the law of cause and effect applies even when it comes to moral and religious phenomena. Because of this, Jayatilleke writes that "Buddhism is not likely to be at variance with science so long as scientists confine themselves to their methodology and their respective fields without making a dogma of materialism."
In a similar fashion, Buddhadasa P. Kirthisinghe, a Theravada Buddhist and a microbiologist, argues that Buddhism and science are compatible because Buddhism is based on a similar method of empirical inquiry, observation and careful analysis which is "in conformity with and in the spirit of science." Bhikkhu Ñanajivako, citing Bertrand Russell's An Outline of Philosophy, writes that modern science's rejection of substance theory in favor of processes or events is commensurate with the Buddhist impermanence (anicca) doctrine, which sees the world made up of transient dhammas.
=== Views of East Asians ===
Erik J. Hammerstrom has written a study of the reception of modern science in 19th and 20th century Chinese Buddhism. According to Hammerstrom, during the 1920s and 30s, "dozens of articles and monographs devoted to the topic of science and Buddhism appeared in the rapidly growing Buddhist press of China." Chinese Buddhists like Taixu, Yang Wenhui, Wang Hui and Wang Xiaoxu (an electrical engineer and lay Buddhist) were some of the leading figures in this discourse. According to Hammerstrom, 20th century Chinese Buddhists championed the scientific method and its findings such as heliocentrism and evolution and generally did not question the findings of science. However, Chinese Buddhists also rejected certain ideas associated with science at the time, such as scientism, materialism and Social Darwinism (and they participated in public debates about such ideas). They also sought to carve out a space for Buddhism as a "philosophy of life" (人生觀, renshengguan) which they saw as a separate field of inquiry.
Not all Buddhist modernists thought that Buddhism could stand on a rationalist scientific framework alone. D.T. Suzuki initially accepted the idea that Buddhism could be founded on scientific principles, writing that karma "may be regarded as an application in our ethical realm of the theory of the conservation of energy (Outlines of Mahayana Buddhism, 1907). However, Suzuki later changed his mind about this, writing in 1959 that "a religion based solely on science is not enough."
Similarly, the Chinese Buddhist modernist Taixu (1890–1947) held that while scientific study might help prove Buddhist doctrines, "it cannot ascertain the realities" of Buddhism and therefore it "does not go far enough into the mysteries of nature, and that if she went further the Buddhist doctrine would be even more evident." Thus, while for Taixu, "the Buddhist scholar is aided in his research" by the use of scientific methods, they must ultimately go beyond such methods to understand the true nature of reality. Taixu wrote that "the reality of the Buddhist doctrine is only to be grasped by those who are in the sphere of supreme and universal perception, in which they can behold the true nature of the Universe, but for this they must have attained the wisdom of Buddha himself, and it is not by the use of science or logic that we can expect to acquire such wisdom. Science therefore is only a stepping stone in such matters"
Trịnh Xuân Thuận, a Vietnamese-American astrophysicist, has also written about Buddhism and science, which he sees as "two complementary modes of knowledge." Thuận disagrees with Stephen Jay Gould, who held the view that science and religion examine two "non-overlapping magisteria." Instead, Thuận thinks they do overlap (since Buddhism is a kind of contemplative science) and as such, there can be "a fruitful and illuminating dialogue" between them.
=== Views of Tibetan Buddhists ===
Similar views of the complementarity of science and Buddhism remain popular in modern Tibetan Buddhism. Gendun Chopel was the first Tibetan Buddhist to write about science and he urged his countrymen to accept the methods of science, which were based on empirical observation and was therefore seen by him as compatible with the epistemic methods of Buddhism (i.e. the pramana of direct perception or pratyakṣa). Chopel writes that science even confirms central Buddhist doctrines such as impermanence and dependent origination, though it can also disprove certain Buddhist views, such as the insentience of plants (and therefore, Buddhists should not stubbornly cling to their doctrine). Chopel argued that Buddhism can only survive as an ally of science and prayed that science and the teachings of the Buddha "may abide together for tens of thousands of years."
More recently, contemporary Tibetan Buddhists like the 14th Dalai Lama, B. Alan Wallace, and Robert Thurman have also argued for the compatibility of Buddhism and science. According to Lopez, "the Fourteenth Dalai Lama of Tibet has been the most visible and influential Buddhist teacher to embrace the discourse of Buddhism and Science." The Dalai Lama is known for his interest in science and has written a book on the relationship between science and Buddhism, The Universe in a Single Atom (2005), where he discusses various topics, including physics and evolution. The Dalai Lama argues that science and Buddhism share the same commitment "to keep searching for reality by empirical means and to be willing to discard accepted or long-held positions if our search finds that the truth is different."
B. Alan Wallace (who has studied physics and Buddhism formally in Western institutions) sees Buddhism as an "organized, systematic enterprise aimed at understanding reality, and it presents a wide range of testable laws and principles," as well as a "time-tested discipline of rational and empirical inquiry." Wallace argues that Buddhism is a mainly pragmatic enterprise aimed at "the pursuit of eudaimonic well-being", and as such, it focuses on the subjective and on qualitative states of consciousness (unlike science, which focuses on the quantifiable and the objective), discussing issues such as mental training and ethics. Wallace also argues that Buddhist insights are roughly empirical, since they are based on direct experiences (of a subjective, first-person character) which are also replicable.
However, the Dalai Lama, Thurman and Wallace all note that Buddhism rejects a materialistic (or physicalist) interpretation of science which sees consciousness as something that arises from physical causes alone. For Wallace, scientific materialism is a metaphysical assumption, a dogma which goes beyond the domain of empirical science and "presents formidable obstacles to any meaningful collaboration between Buddhism and science." Similarly, Robert Thurman criticizes the physicalist interpretation of neuroscience and sees Buddhist meditation as a kind of "inner science" with "a vast array of mental technologies". Thurman also thinks that the materialist worldview has led to an imbalance in the world where "our powers to effect the outer reality have outstripped our powers over ourselves," and sees Buddhist practice as a corrective to this.
The 14th Dalai Lama has explicitly rejected any kind of scientism which would argue that only science can discover truths about the world (and that those truths ultimately reduce to the physical world alone) and thus that anything which is not proven by science is false or insignificant. However, he also argues that "spirituality must be tempered by the insights and discoveries of science. If as spiritual practitioners we ignore the discoveries of science, our practice is also impoverished, as this mind-set can lead to fundamentalism." For the 14th Dalai Lama, science is concerned with conventional truth and understanding the nature of the mundane world, while Buddhism offers "a real under-standing of the true nature of the mind," and the ultimate truth of liberation. Lopez compares this view with the view of Gould's "non-overlapping magisteria."
=== Views of scholars of Buddhism ===
According to one scholar of Buddhism, John Dunne, "Buddhism endorses the notion that if we want to prove something, we need to use empirical evidence." Dunne argues that this principle trumps what the Buddhist scriptures say, since the Buddhist tradition considers direct experience (Sanskrit: pratyakṣa) as a higher source of knowledge than scripture (which is secondary). However, Dunne also notes that Buddhist theories do not undergo constant revision throughout the centuries (as a result of new observations) as they have done in science, though he notes that more recently the 14th Dalai Lama has been interested in learning from science in this regard.
David McMahan has written about the modernist scientific Buddhism discourse. According to McMahan, this discourse should not be dismissed entirely, since modern Buddhist traditions have gone through "a concrete and highly significant transformation", which includes adapting to the scientific worldview and creating new forms of Buddhism. McMahan writes that this:
is not just a western orientalist representation of the eastern Other, nor is it just a native strategy of legitimation for Asian Buddhists, though it does involve both. It is rather a part of the ongoing hybridization of certain forms of Buddhism with distinctively modern cultural formations and intellectual practices. The historical question regarding contemporary Buddhism, then, is not "Is Buddhism scientific?" but "How is Buddhism transforming itself through its engagement with science?" Rather than telling us "what Buddhism is," this discourse is itself constitutive of novel forms of Buddhism with shifting epistemic structures and criteria for authority and legitimacy.
However, McMahan also thinks that there is also the danger of Buddhism losing "a great deal of its diversity" if the adaptation process is taken too far and that "too much adaptation and accommodation may in fact blur the distinctions between the epistemic claims of Buddhism and those of current Western traditions." This could lead to the loss of Buddhist distinctiveness and to the making of Buddhism into an impotent tradition that has nothing to offer to modernity.
According to Geoffrey Samuel, while the dialogue between Buddhism and science has generally focused on ways in which Buddhism can adapt to science or how science can study the efficacy of Buddhist practices, "the more significant developments are arguably elsewhere, in the potential of Buddhist thought to provoke genuine rethinking and transformation within science itself." Similarly, Martin J. Verhoeven thinks that "we might better advance the discussion not by highlighting where Buddhism and science see eye-to-eye, but precisely where they do not, perhaps forcing each to confront its own contradictions and shortcomings." Verhoeven argues that Buddhism and science see reality in different ways. The central focus of Buddhism is on one's conscious experience and its conditioned nature. This includes the external world, which seems separate, but is actually "inescapably conditioned by and of a piece with oneself" and "depends on our position, our interpretations, our intentions, and our desires."
José Ignacio Cabezón writes that there has been an increasing sophistication in the dialogue between science and Buddhism, which he sees as due to the advances in both science and Buddhist studies as well as due to the "increased accessibility of information about these two traditions." Regarding the discourse on complementarity, Cabezón thinks that it may be useful if understood "as a fluid metaphor". However, if understood as a literal and strict binary opposition, it could lead to a stunted dialogue, since both traditions discuss numerous elements that are of interest to the other (for example, Buddhism often discusses physical events and science has much to say about the mind). As such, the "segregationist metaphors" which are often used in the complementarity discourse are ultimately artificial "because scientific claims impinge, and sometimes impinge negatively, upon Buddhist ones, and vice versa." Because of this, Cabezón argues that Buddhism and science are "complete systems that resist dichotomizing: systems that can both support and challenge each other at a variety of different levels."
Professor P. L. Dhar claims that the practice of Buddhism, Dharma, is compatible with the practice of scientific discoveries, as both reflects human tendency to inquire into things. On one hand, in scientific practices we ask questions about the external physical world, and gain knowledge about the facts of the world. On the other hand, in practicing Dharma we inquire about the essence of our own beings, and gain wisdom about our existence.
Gary Zukav points out a new perspective of understanding the significance of science. He writes:
[The laws of Science] are the reflection in physical reality...of a larger non-physical dynamic at work in non-physical domains. When Science and its discoveries are understood with the higher order of logic and understanding of the multisensory human, they reveal the same richness that Life itself displays everywhere and endlessly.
According to Zukav, the significance of science lies in its reflection of the relationship between our own being and the external world. This point can be illustrated with specific branches of science. For example, Newtonian physics - a classical notion of physical world characterised by axiomatic equations and general laws of motion, reflects our desire and assertiveness not only to discover physical facts about the world by scientific induction, but also to make use of our discoveries in a constructive way. There are many ways to further clarify this example, and here is one such way. As a founding figure of modern science, Francis Bacon contributed towards the enlightenment movement by popularizing the term ''knowledge is power'', which implicitly sanctions not only the manipulation, but also potentially the exploitation, of the natural world. This shows the potential that conventional modern science can be overpowering and lack balance; meanwhile, the practice of Buddhism can act as a counter-balance to science: ''Science without Dharma is blind and Dharma without Science is lame. ''
==== Criticism of the Buddhist modernist discourse ====
Several contemporary scholars of Buddhism have argued against the idea that Buddhism is a science or "scientific". According to Donald S. Lopez Jr., the traditional Buddhist worldview understands the Buddha's ancient understanding of reality as complete, and thus "nothing beyond that reality has been discovered since." Lopez argues that attempts to make Buddhism compatible with science severely restrict Buddhism, "eliminating much of what has been deemed essential, whatever that might be, to the exalted monks and ordinary lay-people who have gone for refuge to the Buddha over the course of more than two thousand years." Lopez argues that in traditional Buddhism, the truth is something that the Buddha has already discovered, making Buddhism a deeply conservative tradition which is wary of innovation and deviation. This is different from the scientific worldview, in which the complete truth of the universe has not been fully discovered yet.
Lopez has also described the historical development which led to the idea that Buddhism was compatible with science, which began in the Victorian era, with the European study of Buddhist literature in Indian languages (Sanskrit and Pali). Western scholars often saw the historical Buddha as a rational humanist, critical of Brahmanical superstition. This idea was then taken up by Asians and theosophists and widely promoted as a counter to missionary Christianity. Lopez thinks that the "scientific" Buddhism discourse is outdated, especially since the colonial and missionary threats to Buddhism in Asia have subsided. Lopez argues it is best to see Buddhism as radically incompatible with science, as seeking to transcend all biological life, to go totally beyond the world and thus as being at odds with the world and with science. However, Lopez also notes that disputes between Buddhists and scientists over the bare facts of science "have occurred only rarely in the history of Buddhism and science."
Evan Thompson has also criticized the narrative of Buddhism as being uniquely scientific in his Why I am Not a Buddhist (2020).
== Buddhism and specific scientific fields ==
=== Biology ===
Modern Buddhists have generally accepted and embraced modern theories of biology, such as evolution, as being compatible with Buddhist thought. According to a 2009 survey by the Pew Research Center, eighty one percent of Buddhists accept the theory of evolution as the "best explanation for the origins of human life on earth" (the highest among all religions surveyed).
Robin Cooper's The Evolving Mind (1996) is one publication which discusses Buddhism and the field of biology. Cooper argues that Buddhism is compatible with evolutionary thought, but he also argues that the Buddhist view also sees a role for the mind in the evolution of living beings. Cooper writes that mind-led adaptations also play a role in evolution, along with random genetic mutation. He attempts to harmonize biological theories of evolution with Buddhist views of the transformation of the mind.
William S. Waldron cites the Agañña sutta as a text which affirms that sentient beings, including humans, change over time. However this discourse describes a process in which heavenly beings (devas) devolve into a lower form of life on earth as a result of mental afflictions or kleshas (such as greed and desire) and the actions fueled by these afflictions. As such, Buddhism sees our physical existence as being caused by past actions (done in our previous lives). Waldron thinks that this view is roughly compatible (but clearly not the same as) the theory of evolution, which holds that our current physical form is based on the past actions of our ancestors. According to Waldron, "the Buddhists and biologists thus largely concur that the very forms and structures of human life result from the accumulative actions of innumerable beings over countless generations."
David P. Barash (who describes himself as a Buddhist atheist) has written a book about Buddhism and biology, which according to him, "complement each other like a pair of powerful searchlights illuminating the same thing from different angles". Barash argues that modern biology is commensurate with the Buddhist view of impermanence and not-self, since both see sentient beings (individuals or groups) as a product of constantly changing and interrelated processes, and thus sees them as being without a fixed and separate identity.
==== Key differences ====
Donald Lopez argues that the naturalistic theory of evolution is at odds with the traditional Buddhist view of karma. This is because the basic Buddhist understanding of how sentient beings undergo change is based on the rebirth of their consciousness, which could be into any form of existence (animal, human, god realms etc.), while the Darwinian view is strictly based on genetic mutation and natural selection which are physical phenomena. According to Lopez, the main reason these views are at odds is that Buddhism reserves a central place for consciousness and volition in the production of all sentient life, while this is not the case with modern biology.
In The Universe in a Single Atom (2005), the 14th Dalai Lama similarly points outs that while biological theories generally attempts to explain things solely from the perspective of physical causes (and are often reductive), Buddhist thought focuses on the role of consciousness. As such, the Dalai Lama finds theories which focus only on physical causes "deeply unsatisfying", since it seems difficult to explain how conscious beings can arise from an unconscious basis (i.e. emergentism). He also points out that this difference might be due to the different methods and goals of Buddhism and science. Therefore, while the Dalai Lama thinks that evolution "gives us a fairly coherent account of the evolution of human life on earth," he also holds that karma and consciousness have central roles in nature and therefore biology cannot explain all aspects of life (such as consciousness, religious experience or morality).
=== Physics ===
According to Matthieu Ricard, Buddhist thought asks some of the same questions that physicists ask about reality, time, matter and space, and uses rational analysis and thought experiments (which are also used by physicists). However, unlike physics which focuses on measuring the physical world to better understand it, the Buddhist tradition focuses on inner contemplation and its goal is mainly therapeutic.
Some of the metaphysical doctrines of Buddhism have sometimes been compared favorably with the insights of modern physics. The 14th Dalai Lama writes in The Universe in a Single Atom (2005) that "there is an unmistakable resonance between the notion of emptiness and the new physics. If on the quantum level, matter is revealed as less solid and definable than it appears, then it seems to me that science is coming closer to the Buddhist contemplative insights of emptiness and interdependence [pratītyasamputpāda]."
The Dalai Lama cites his conversations with David Bohm and Anton Zeilinger, both physicists who supported the idea that the Buddhist view of emptiness (the lack of any independent and fixed essence) was consistent with the insights of modern quantum physics. The Dalai Lama has also been part of various dialogues with physicists such as Arthur Zajonc (who was also president of the Mind and Life Institute) and Anton Zeilinger. Some of these discussions on the nature of physics have been published.
==== Comparisons by physicists ====
Astrophysicist Trịnh Xuân Thuận argues that the Buddhist idea of "subtle impermanence", which refers to the idea that everything is constantly changing extremely rapidly is consistent with "our modern scientific conception of the universe" which holds that everything is in constant motion. He also compares the Buddhist doctrine of emptiness (the idea that nothing has an intrinsic nature) with the findings of quantum physics, which understands that sub-atomic particles cannot be understood as being real solid entities with fixed properties such as momentum and position (this is one understanding of the Heisenberg uncertainty principle). Thuận cites Erwin Schrödinger who said that "it is better not to view a particle as a permanent entity, but rather as an instantaneous event. Sometimes these events link together to create the illusion of permanent entities." Thuận sees this understanding of sub-atomic particles as similar to the understanding of reality in Buddhist metaphysics.
Thuận and Matthieu Ricard also discuss the similarities between Buddhist views of interdependence and phenomena such as quantum nonlocality and Mach's principle in The quantum and the lotus. According to Thuận, the views of Bohr and Heisenberg seem to support the Buddhist view that physical particles do not exist as independent phenomena, but can only be said to exist in dependence on our conceptual designations and the process of observation. This view of the quantum world is sometimes called the Copenhagen interpretation.
The Italian theoretical physicist Carlo Rovelli cites Nagarjuna in his book Helgoland, a defense of the relational interpretation of quantum mechanics, which understands quantum properties as arising from the relations between quantum phenomena. According to Rovelli, "properties of an object are the way in which it acts upon other objects; reality is this web of interactions." Rovelli thinks that the Madhyamaka philosophy of Nāgārjuna resonates with the relational view of Quantum Mechanics and provides a conceptual understanding of reality that does not need a metaphysical foundation. Rovelli writes that "Nāgārjuna has given us a formidable conceptual tool for thinking about the relationality of quanta: we can think of interdependence without autonomous essence entering the equation."
Oxford physicist Vlatko Vedral, in his Decoding Reality, mentions the Buddhist theory of emptiness as an ancient example of the philosophy of "relationalism." Vedral, who argues for an interpretation of quantum physics based on information theory, states that "Quantum physics is indeed very much in agreement with Buddhistic emptiness." He states that "we will never arrive at 'the thing in itself' by any kind of means. Everything that exists, exists by convention and labelling and is therefore dependent on other things." This is similar to some forms of Buddhist philosophy (such as Madhyamaka) which hold that everything is merely conceptual.
Physics professor Vic Mansfield has also written on the similarities between the modern understanding of time and special relativity and Madhyamaka thought. According to Mansfield, an appreciation of how these two traditions understand time as a relative phenomenon can aid a deeper understanding of both and that "a nontrivial synergy between these two very different disciplines is possible." Mansfield also argues that this kind of dialogue is important for Buddhism because "if Buddhism is to come to the West, in the best and fullest sense of the term, then interaction with science is both inevitable and necessary for a real transplant to take place."
=== Cosmology ===
In his discussion of cosmology, the 14th Dalai Lama notes that "Buddhism and science share a fundamental reluctance to postulate a transcendent being as the origin of all things." Furthermore, Buddhists like the Dalai Lama have no problem accepting the Big Bang theory (since ancient Buddhist views about the cosmos accept that there are periods of expansion). However, Trịnh Xuân Thuận and the Dalai Lama both argue that from the Buddhist point of view, there is no absolute beginning to the universe. This would be more compatible with certain cosmogonic theories of the universe, such as those that posit a Cyclic model of the universe or those that argue for a multiverse.
There are different Buddhist cosmologies. The cosmology of the Kalachakra system popular in Tibetan Buddhism holds that the material world arises out of the supportive element of space, which is made up of "space particles", the other four elements arise from this medium. The Dalai Lama believes this is compatible with the idea that the universe arose from a quantum vacuum state.
The Dalai Lama also notes that in Buddhist cosmology, there is a role for consciousness and karma, since Buddhist systems hold that the nature of a world system is connected with the karmic propensities of sentient beings. However, the Dalai Lama points out that this does not mean everything is due to karma, since many things merely arise due to the works of natural laws. As such, the Dalai Lama argues that "the entire process of the unfolding of a universe system is a matter of the natural law of causality" but that karma also influences its very beginning and that when a universe is able to support life "its fate becomes entangled with the karma of the beings who will inhabit it." Because Buddhist thought sees consciousness as being interconnected with the physical world, Buddhists like the Dalai Lama hold that "even the laws of physics are entangled with the karma of the sentient beings that will arise in that universe."
==== Traditional cosmography ====
Certain traditional Buddhist ideas about the world are also incompatible with modern science, and have been abandoned by numerous modern Buddhists. Perhaps one of the most well known of these ideas is the view of the world found in various classic Buddhist texts which holds there is a giant mountain at the center of the world called Mount Meru (or Sumeru). According to Lopez, "the human realm that Buddhist texts describe is a flat earth, or perhaps more accurately a flat ocean, its waters contained by a ring of iron mountains. In that ocean is a great central mountain, surrounded in the four cardinal directions by island continents."
As Lopez notes, as early as the 18th century, Buddhist scholars like Tominaga Nakamoto (1715–1746) began to question this classical Buddhist cosmography, holding that they were adopted by the Buddha from Indian theories, but that they were incidental and thus not at the heart of Buddha's teaching. While some traditional Buddhists did defend the traditional cosmology, others like Shimaji Mokurai (1838–1911) argued that it was not foundational to Buddhism and was merely an element of Indian mythology. Others like Kimura Taiken (1881–1930), went further and argued that this traditional cosmography was not part of original Buddhism.
The issue of Mount Meru was also discussed by modern Buddhist intellectuals like Gendun Chopel and the 14th Dalai Lama. According to Choepel, the Meru cosmology is a provisional teaching taught in accord with the ideas of ancient India, but not appropriate for the modern era. Similarly, the 14th Dalai Lama writes that "my own view is that Buddhism must abandon many aspects of the Abhidharma cosmology". The Dalai Lama sees the falsehood of this traditional cosmology as not affecting the core of Buddhism (the teaching of the Four Noble Truths and liberation) since it is "secondary to the account of the nature and origins of sentient beings".
=== Psychology ===
In the 20th century, Buddhism has been in close contact with the field of psychology and has often been interpreted as a kind of psychology in its own right. In America, William James often drew on Buddhist ideas (which he saw as the psychology of the future). Influenced by Buddhism, James promoted meditation and coined the term "stream of consciousness". Another 20th century defender of Buddhism was Gerald Du Pre, who saw Buddhism as a "scientific psychology".
Various modern therapists have written on the relationship between Buddhism and psychotherapy. These include Mark Epstein (Thoughts Without a Thinker 1995, Psychotherapy Without the Self, 2008), Jeffrey B. Rubin, Andrew Olendzki and Nina Coltart (1927–1997).
Various authors such as William S. Waldron and David Galin have also written about the Buddhist theory of not-self (anatman) and how it can provide insights to the development of a more dynamic, conditional and constructivist views of personality, personal identity and the self. Daniel Goleman has argued that the Buddhist view of the emptiness of the self "may turn out to fit the data far better than the notions that have dominated Psychological thinking for the last century."
Robert Wright has argued (in his 2017 Why Buddhism Is True) that the Buddhist analysis of human suffering and delusion is fundamentally correct and that this is backed up by evolutionary psychology, which helps explain how natural selection hardwired humans with powerful but distorted cognitions and emotions which are effective at getting us to survive and pass on our genes in a pre-historic environment. These cognitive modules do not depict reality as it is, and do not often lead to well being. Wright also thinks that the Buddhist view of not-self (anatta) is compatible with modern psychological understandings of the mind. He cites various modern studies and psychological theories (such as the modular view of the mind defended by Michael Gazzaniga) to back up the idea that there is no "CEO" in control of the mind. Wright argues that Buddhist mindfulness meditation can provide a way to gain personal insights into these delusions and may help weaken their hold on us.
The field of Transpersonal psychology has also been influenced by Buddhist ideas and various figures in this field see Buddhism and western psychology as complementary, since each provides a structure of human development that is not found in other (contemplative development and developmental psychology respectively). According to José Ignacio Cabezón, this idea "has been put forward most clearly and forcefully" in Transformations of Consciousness (Wilber, Engler, and Brown 1986), a collection of essays from the Journal of Transpersonal Psychology. However, Cabezón is unconvinced by the attempts of these figures to present a single and unified structure of meditative development (which they source from various traditions, including Buddhism).
=== Mindfulness and meditation research ===
Buddhist spiritual practices like meditation have also been compared to cognitive behavioral therapy techniques. During the late 20th century, numerous studies were conducted on the psychological effects of certain Buddhist meditation practices (such as vipassana and zazen). Furthermore, Buddhist mindfulness practices influenced the development of new forms of cognitive therapies, which are known as mindfulness-based cognitive therapies. One of the most influential of these therapies is Jon Kabat-Zinn's Mindfulness-based stress reduction (MBSR).
The growing popularity of Buddhist meditation and Buddhist influenced mindfulness meditation has also led to research on the physiological and neurological effects of meditation practices (carried out by figures such as Richard Davidson) as well as to dialogues on the nature of the human mind, which have been enthusiastically encouraged by the present Dalai Lama, Tenzin Gyatso. One of the first westerners to study the neurology of meditation was James H. Austin, the author of Zen and the Brain (1998). A more recent overview of related research findings can be found in Davidson and Goleman's Altered Traits, which discusses studies done with the aid of Buddhist monks like Matthieu Ricard and Mingyur Rinpoche. The number of studies on Buddhist and Buddhist-derived meditation techniques skyrocketed in the 21st century (in 2015, there were 674 such studies) and their results were widely reported in the popular press. This also led to a cottage industry of popular books on Buddhist and mindfulness meditation and the adoption of secularized meditation in major corporations.
William Edelglass has argued that the modern study of meditation and happiness is implicitly founded on a Western notion of happiness as positive affect or pleasure (which are most often measured through experience sampling and self-reporting). Edelglass contrasts this notion of happiness with the Buddhist view found in the work of Śāntideva and other ancient Buddhist sources that sees meditation (and other virtues, such as the six perfections) as ways to develop wisdom and transform oneself in a radical, highly ethical fashion by letting go of all attachments. The Buddhist perspective also rejects sensual pleasures as worthless and is opposed to the maximization of positive affect for its own sake (indeed, it sees this as counterproductive).
=== Cognitive science ===
Various studies have shown that Buddhist and mindfulness meditators experience long term transformations in cognitive function and neural activity. However, as Jay L. Garfield notes, this should not be surprising (to scientists or to Buddhists), since meditation is one kind of cognitive expertise and it is therefore normal that it should have neural correlates. Similarly, for Buddhists, the interdependence of mind and body is an ancient view.
Garfield also argues that cognitive science might have much to contribute to the development of Buddhist philosophy, since ancient Buddhist thinkers do not discuss important issues related to attention, memory and perception (such as inattentional blindness). Furthermore, the Buddhist epistemic focus on an empirical understanding of causal processes "commits Buddhists theorists of mind to attend to contemporary scientific results concerning the mind." Garfield thinks that the greatest contribution that Buddhism can make lies in the field of moral psychology and positive psychology, which is highly sophisticated in Buddhist thought.
Evan Thompson writes that the neuroscientific study of mindfulness tends to view mindfulness a private inner observation (or meta-awareness) which is then conceptualized as neural networks that are studied in brain imaging tools. Thompson thinks this confuses the biological markers for mindfulness (such as decreased amygdala reactivity, relative deactivation of the default-mode network, and slower baseline respiration rate) for mindfulness itself, which is actually "a host of cognitive, affective, and bodily skills" which are situated in an ethical way of life and in a particular socio-cultural setting. Thompson thinks that applying insights from embodied cognition, such as the "enactive approach to cognition", can help Buddhist scholars understand better how mindfulness functions as an aspect of the entire embodied person and how it relates to the study of mediation, which would more effectively be done through the perspective of cognitive ecology.
Similarly, David McMahan thinks that Buddhist meditation practices are situated in specific religious, conceptual and socio-cultural contexts, that is, ways of being-in-the-world (referring to "Lifeworlds" and "social imaginaries"). These ways of being are altered, secularized, modernized and abstracted out when Buddhist meditation is studied in a clinical setting and viewed in terms of an individual's internal states that are caused by the meditation technique. According to McMahan, the general assumption of those who study meditation is that meditation techniques can be studied in isolation, but this is likely to be mistaken since "meditation "works" as a systemic part of the ecology of a sociocultural system." A similar contextual critique has been put forth by Robert H. Sharf.
==== The problem of scientific materialism ====
Buddhism rejects all materialistic theories which attempt to reduce consciousness to the functions of physical properties. The 14th Dalai Lama states that "from the Buddhist perspective, the mental realm cannot be reduced to the world of matter, though it may depend upon that world to function." Because of this, while Buddhists like the Dalai Lama embrace the findings and methods of neuroscience, they do not accept the assumptions of some neuroscientists that consciousness can be fully explained as a function of the brain (which is a metaphysical assumption). He further argues that "there is as yet no scientific basis for such a categorical claim," since neuroscience mainly studies correlations between brain states and first person pare "grounded in the phenomenology of experience" and "include the contemplative techniques of meditation" could assist in the development of a more holistic cognitive science that makes use of introspection. The Dalai Lama sees these methods as first person empirical processes.
This idea is also supported by B. Alan Wallace, who argues that modern cognitive science is held back by materialist assumptions and its desire to study consciousness (which is subjective and qualitative) through quantitative measuring of its physical correlates. However, since Wallace argues that the correlates of consciousness are not equivalent to consciousness itself, this method creates a blind spot in cognitive science (which also ignores the hard problem of consciousness). Wallace argues that the contemplative skills found in traditions like Buddhism can aid in the development of a rigorous form of introspection which could be used in cognitive science to deliver a better understanding of the mind.
Geoffrey Samuel notes how the Buddhist point of view has often clashed with the reductionist and materialistic assumptions of many modern neuroscientists. He suggests that the question of personal identity and the self "might provide an important starting point" for a critical revision of the assumptions of modern science which focuses on the study of individual brains. He points to the 'enactive' and 'ecological' approach to consciousness by figures like Francisco Varela and Gregory Bateson as a more fruitful ground for the dialogue between Buddhism and science, since these theories "see cognition, and consciousness in general, as part of an ongoing process in which both 'world' and 'mind' are constituted through mutual interaction". According to Samuel, Varela "argued that the upwards causation of conventional neuroscience, in which consciousness is seen as derivative of the body, needs to be complemented by a downwards causation from the emergent structures of the self, which develop within the neural system as part of the process of maturation of each human being".
== Buddhism and other related fields ==
=== History of science ===
José Ignacio Cabezón has discussed how historians of science seek to understand the origins of science and why its rise was much more successful in Europe. Some of these figures such as Stanley Jaki have argued that it is because Europe was dominated by the Christian worldview (with its linear view of time and de-animized view of nature) that it gave rise to modern science, while this could not have happened in Buddhist Asia (which generally held a cyclic view of time and accepted polytheism/animism).
However, Cabezón notes that India and China "did give rise to forms of empirically derived sciences that can be recognized as such even in Western terms." He points to the work of Joseph Needham (author of the long running series of books called Science and Civilisation in China) as an example. Furthermore, Cabezón also notes that neither animism nor a cyclic theory of time "acted as deterrents to the acceptance of science in these various cultures since its movement east, something that would be expected were Jaki's thesis true." On the contrary, these religious cultures embraced science rapidly.
=== Philosophy of science ===
B. Alan Wallace's Choosing Reality (1996) is one work which discusses Buddhism in regards to the philosophy of science. Wallace argues that science is not metaphysically neutral, and that the two main metaphysical views in the philosophy of science have been scientific realism and instrumentalism. Wallace thinks these two theories fail to provide a proper philosophical foundation for science and instead argues in favor of the Buddhism Madhyamaka philosophy. Wallace also argues that Buddhism can complement science by providing a spirit of responsibility and service for others, a spirit that has been lost as science became separated from religion and philosophy.
In Hidden Dimensions (2007), Wallace also cites the ideas of some modern physicists which have argued for alternative ontologies to materialism or physicalism. These figures include Bohm (and his "implicate order"), Wolfgang Pauli's idea (developed along with Jung) of the unus mundus, George Ellis' fourfold model of reality (matter and forces, consciousness, physical and biological possibilities, and mathematical reality) as well as the views of Eugene Wigner and Bernard d'Espagnat.
Wallace has also compared John Archibald Wheeler's participatory anthropic principle (which sees scientific concepts like matter, mass and so on as "creations of the human mind, not discovered in the pre-existing, objective world of nature") to the Madhyamaka view which sees a deep interdependence between subjects and objects. Wallace thinks that "such parallels suggest that meaningful theoretical collaboration could take place between physicists and Buddhist philosophers and contemplatives."
Mark T. Unno sees the ontology of David Bohm as being similar to the Mahayana Buddhist philosophy of the twofold truth (of form and emptiness). According to Unno, David Bohm "suggests that mind and matter, thought and thing, are mutually implicit, as are all other phenomena, such that there is a wholeness to the universe in which all distinctions ultimately dissolve." Since, for Bohm, "there is no definable divide between mind and matter," there is a kind of wholeness to the universe which cannot be understood conceptually or discursively, but "can only be ultimately realized in the present moment, inseparable from the subject." According to Unno, the same is true for the Buddhist view of emptiness. This is not surprising, since according to Unno, Bohm was "influenced by Indian philosopher Jiddu Krishnamurti and Buddhist thinkers such as the Dalai Lama."
==== Philosophy of physics ====
Michel Bitbol has argued that Buddhist Madhyamaka philosophy can help provide a useful philosophical framework for quantum mechanics. According to Bitbol, there isa thorough and detailed structural analogy between quantum contextuality and Buddhist Śūnyatā (emptiness of own-being); and between quantum entanglement and Buddhist Pratîtyasamutpâda (dependent origination). But this twofold analogy does not show that there is a single essence of reality which can be disclosed by our reason irrespective of whether we rely on an experimental approach or a contemplative approach. The analogy rather shows that, at a sufficiently accurate level of analysis and careful attention, the negative conclusions of experimental physicists and contemplative Buddhists are bound to be similar: both realize the approximative status of the reified entities of everyday life, and both must cope with the high amount of instability and lack of self-sufficient existence (Śūnyatā) of phenomena. Then, if thoroughly applied, the critical concept of Śūnyatā can be seen to underpin the anti-metaphysical stances of both Buddhism and certain trends in the contemporary philosophy of science. The American physicist David Ritz Finkelstein developed a theory of "universal relativity," influenced by Madhyamaka philosophy and his discussions at the Mind and Life dialogues. Finkelstein believes that "a philosophical argument for a universal relativity could be a useful guide for future physics," since "the major changes in physics in this century have been extensions of relativity at one level or another, and I think a further extension is due." Finkelstein's theory is based on the view that all laws of nature are ultimately relative and non-absolute. In this theory, doing (change) and knowing (attempting to fix a process in place) are relative elements.
==== Anthropic principle ====
Matthieu Ricard, commenting on the question of the anthropic principle and fine-tuning (which states that life is dependent on certain fundamental physical constants whose exact values are improbable), states that:As far as Buddhism is concerned, the idea that there is some principle of organization that is supposed to have tuned the universe perfectly so that the conscious mind could evolve is fundamentally misguided. The apparently amazing fine-tuning is explained simply by the fact that the physical constants and consciousness have always coexisted in a universe that has no beginning and no end.... The universe has not been adjusted by a great watchmaker so that consciousness can exist. The universe and consciousness have always coexisted and so cannot exclude each other. To coexist, phenomena must be mutually suitable. The problem with the anthropic principle, or any other teleological theory, is that it puts the constants before consciousness and thus claims that the constants exist only so that they can create consciousness.
=== Artificial intelligence ===
== Modern reception ==
=== Modern scientists on Buddhism ===
Niels Bohr, who developed the Bohr Model of the atom, said,
For a parallel to the lesson of atomic theory...[we must turn] to those kinds of epistemological problems with which already thinkers like the Buddha and Lao Tzu have been confronted, when trying to harmonize our position as spectators and actors in the great drama of existence.
The American physicist J. Robert Oppenheimer made an analogy to Buddhism when describing the Heisenberg uncertainty principle:
If we ask, for instance, whether the position of the electron remains the same, we must say 'no;' if we ask whether the electron's position changes with time, we must say 'no;' if we ask whether the electron is at rest, we must say 'no;' if we ask whether it is in motion, we must say 'no.' The Buddha has given such answers when interrogated as to the conditions of man's self after his death; but they are not familiar answers for the tradition of seventeenth and eighteenth-century science.
Nobel Prize–winning physicist Albert Einstein, who developed the general theory of relativity and the special theory of relativity, also known for his mass–energy equivalence, described Buddhism as containing a strong cosmic element:
...there is found a third level of religious experience, even if it is seldom found in a pure form. I will call it the cosmic religious sense. This is hard to make clear to those who do not experience it, since it does not involve an anthropomorphic idea of God; the individual feels the vanity of human desires and aims, and the nobility and marvelous order which are revealed in nature and in the world of thought. He feels the individual destiny as an imprisonment and seeks to experience the totality of existence as a unity full of significance. Indications of this cosmic religious sense can be found even on earlier levels of development—for example, in the Psalms of David and in the Prophets. The cosmic element is much stronger in Buddhism, as, in particular, Schopenhauer's magnificent essays have shown us. The religious geniuses of all times have been distinguished by this cosmic religious sense, which recognizes neither dogmas nor God made in man's image. Consequently there cannot be a church whose chief doctrines are based on the cosmic religious experience. It comes about, therefore, that we find precisely among the heretics of all ages men who were inspired by this highest religious experience; often they appeared to their contemporaries as atheists, but sometimes also as saints.
=== Modern Buddhists on science ===
The 14th Dalai Lama is known for his interest in science and has gone on record to say that Buddhism must conform to proven scientific findings:My confidence in venturing into science lies in my basic belief that as in science so in Buddhism, understanding the nature of reality is pursued by means of critical investigation: if scientific analysis were conclusively to demonstrate certain claims in Buddhism to be false, then we must accept the findings of science and abandon those claims.The Dalai Lama argues that science and spirituality are related, though they work on different levels:The great benefit of science is that it can contribute tremendously to the alleviation of suffering at the physical level, but it is only through the cultivation of the qualities of the human heart and the transformation of our attitudes that we can begin to address and overcome mental suffering. In other words, the enhancement of fundamental human values is indispensable to our basic quest for happiness. Therefore, from the perspective of human well-being, science and spirituality are not unrelated. We need both, since the alleviation of suffering must take place at both the physical and psychological levels.
== See also ==
== Notes ==
== References ==
== Sources ==
De Silva, Padmasiri (2005) An Introduction to Buddhist Psychology, 4th edition, Palgrave Macmillan.
Clayton, Philip (editor) (2006). The Oxford Handbook of Religion and Science. Oxford University Press.
Goleman, Daniel (in collaboration with The Dalai Lama), Destructive Emotions, Bloomsbury (London UK 2003)
Gyatso, Tenzin (The 14th Dalai Lama) (2005). The Universe in a Single Atom: The Convergence of Science and Spirituality. Morgan Road Books. ISBN 0-7679-2066-X
Hammerstrom, Erik J. (2015). The Science of Chinese Buddhism: Early Twentieth-Century Engagements. Columbia University Press.
Kirthisinghe, Buddhadasa P. (editor) (1993) Buddhism and Science. Motilal Banarsidass.
McMahan, David, "Modernity and the Discourse of Scientific Buddhism." Journal of the American Academy of Religion, Vol. 72, No. 4 (2004), 897–933.
McMahan, David L.; Braun, Erik (2017). Meditation, Buddhism, and Science. Oxford University Press.
Numrich, Paul David. (2008). The Boundaries of Knowledge in Buddhism, Christianity, and Science. Vandenhoeck & Ruprecht.
Lopez Jr., Donald S. (2009). Buddhism and Science: A Guide for the Perplexed. University of Chicago Press.
Lopez Jr., Donald S. (2012). The Scientific Buddha: His Short and Happy Life. Yale University Press.
Rapgay L, Rinpoche VL, Jessum R, Exploring the nature and functions of the mind: a Tibetan Buddhist meditative perspective, Prog. Brain Res. 2000 vol 122 pp 507–15
Ricard, Matthieu; Trinh Xuan Thuan (2009). The Quantum and the Lotus: A Journey to the Frontiers Where Science and Buddhism Meet, Crown Publishers, New York.
Robin Cooper, The Evolving Mind: Buddhism, Biology and Consciousness, Windhorse (Birmingham UK 1996)
Sarunya Prasopchingchana & Dana Sugu, 'Distinctiveness of the Unseen Buddhist Identity' (International Journal of Humanistic Ideology, Cluj-Napoca, Romania, vol. 4, 2010)
Sharf, Robert H. "Buddhist Modernism and the Rhetoric of Meditative Experience." Numen 42, no. 3 (1995a): 228–83.
Wallace, B. Alan (2007). Hidden Dimensions: The Unification of Physics and Consciousness (Columbia Univ Press)
Wallace, B. Alan (2003) (ed), Buddhism and Science: breaking new ground (Columbia University Press) ISBN 0-231-12334-5
Wallace, B. Alan (1996), Choosing Reality: A Buddhist Perspective of Physics and the Mind, (Snow Lion 1996)
Wright, Robert (2017). Why Buddhism is True: The Science and Philosophy of Meditation and Enlightenment. Simon and Schuster.
Zajonc, Arthur (editor) (2004). The New Physics and Cosmology: Dialogues with the Dalai Lama. Oxford University Press
== External links ==
https://www.lionsroar.com/monastic-scholars-journey/ How Buddhism Met Science: A Monastic Scholar’s Journey
The Mind and Life Conferences
Buddha on the Brain – Dalai Lama on the Society for Neuroscience's annual conference
Dalai Lama joining discussions on "Robotics, Telepresence and Artificial Intelligence" and "Sickness, Aging and Health" at De Nieuwe Kerk in Amsterdam, Netherlands | Wikipedia/Buddhism_and_science |
Science and Religion: Some Historical Perspectives is a book on the relationship between religion and science by John Hedley Brooke.
The book identifies three traditional views of the relationship between science and religion found in historical analyses: conflict, complementarity, and commonality. The book portrays all three as oversimplifications. It offers up the alternative notion of complexity, which bases the relationship between science and religion on changing circumstances where it is defined upon each particular historical situation and the actual beliefs and ideas of the scientific and religious figures involved.
== Reception ==
American Historical Review states that the book's bibliographic essay "identifies and … incorporates the results of virtually every significant and relevant article published in the past fifty years."
== References ==
== Further reading ==
Brooke, John H. (1998). "Essays on Science And Society: Science and Religion: Lessons from History?". Science. 282 (5396): 1985–1986. Bibcode:1998Sci...282.1985B. doi:10.1126/science.282.5396.1985. S2CID 159909162.
== List of reviews ==
Cantor, Geoffrey (1992). "Science and Religion (Book Reviews)". The Times Literary Supplement (4639): 27.
Howell, Kenneth J. (December 1994). "Book Review: Science and Religion: Some Historical Perspectives. John Hedley Brooke, George Basalla". The Journal of Modern History. 66 (4): 779–782. doi:10.1086/244944.
Olson, Richard; Brooke, John Hedley (February 1994). "Reviews of Books: Science and Religion Some Historical Perspectives" (PDF). American Historical Review. 99 (1). American Historical Association: 191–192. doi:10.2307/2166181. hdl:1887/10459. JSTOR 2166181.
Pallin, David A. (1992). "Reviews: Science and Religion: Some Historical Perspectives". The Journal of Theological Studies. 43 (2): 797–800. doi:10.1093/jts/43.2.797.
Tollefson, R.J. (1992). "Science and Religion (Book Reviews)". Choice: Current Reviews for Academic Libraries. 29 (8): 1244–1245. | Wikipedia/Science_and_Religion:_Some_Historical_Perspectives |
The relationship between religion and science involves discussions that interconnect the study of the natural world, history, philosophy, and theology. Even though the ancient and medieval worlds did not have conceptions resembling the modern understandings of "science" or of "religion", certain elements of modern ideas on the subject recur throughout history. The pair-structured phrases "religion and science" and "science and religion" first emerged in the literature during the 19th century. This coincided with the refining of "science" (from the studies of "natural philosophy") and of "religion" as distinct concepts in the preceding few centuries—partly due to professionalization of the sciences, the Protestant Reformation, colonization, and globalization. Since then the relationship between science and religion has been characterized in terms of "conflict", "harmony", "complexity", and "mutual independence", among others.
Both science and religion are complex social and cultural endeavors that may vary across cultures and change over time. Most scientific and technical innovations until the scientific revolution were achieved by societies organized by religious traditions. Ancient pagan, Islamic, and Christian scholars pioneered individual elements of the scientific method. Roger Bacon, often credited with formalizing the scientific method, was a Franciscan friar and medieval Christians who studied nature emphasized natural explanations. Confucian thought, whether religious or non-religious in nature, has held different views of science over time. Many 21st-century Buddhists view science as complementary to their beliefs, although the philosophical integrity of such Buddhist modernism has been challenged. While the classification of the material world by the ancient Indians and Greeks into air, earth, fire, and water was more metaphysical, and figures like Anaxagoras questioned certain popular views of Greek divinities, medieval Middle Eastern scholars empirically classified materials.
Events in Europe such as the Galileo affair of the early 17th century, associated with the scientific revolution and the Age of Enlightenment, led scholars such as John William Draper to postulate (c. 1874) a conflict thesis, suggesting that religion and science have been in conflict methodologically, factually and politically throughout history. Some contemporary philosophers and scientists, such as Richard Dawkins, Lawrence Krauss, Peter Atkins, and Donald Prothero subscribe to this thesis; however, historians such as Stephen Shapin state "it is a very long time since these attitudes have been held by historians of science."
Many scientists, philosophers, and theologians throughout history, from Augustine of Hippo to Thomas Aquinas to Francisco Ayala, Kenneth R. Miller, and Francis Collins, have seen compatibility or interdependence between religion and science. Biologist Stephen Jay Gould regarded religion and science as "non-overlapping magisteria", addressing fundamentally separate forms of knowledge and aspects of life. Some historians of science and mathematicians, including John Lennox, Thomas Berry, and Brian Swimme, propose an interconnection between science and religion, while others such as Ian Barbour believe there are even parallels. Public acceptance of scientific facts may sometimes be influenced by religious beliefs such as in the United States, where some reject the concept of evolution by natural selection, especially regarding Human beings. Nevertheless, the American National Academy of Sciences has written that "the evidence for evolution can be fully compatible with religious faith",
a view endorsed by many religious denominations.
== History ==
=== Concepts of science and religion ===
The concepts of "science" and "religion" are a recent invention: "religion" emerged in the 17th century in the midst of colonization, globalization and as a consequence of the Protestant reformation. "Science" emerged in the 19th century in the midst of attempts to narrowly define those who studied nature. Originally what is now known as "science" was pioneered as "natural philosophy".
It was in the 19th century that the terms "Buddhism", "Hinduism", "Taoism", "Confucianism" and "World Religions" first emerged. In the ancient and medieval world, the etymological Latin roots of both science (scientia) and religion (religio) were understood as inner qualities of the individual or virtues, never as doctrines, practices, or actual sources of knowledge.
The 19th century also experienced the concept of "science" receiving its modern shape with new titles emerging such as "biology" and "biologist", "physics", and "physicist", among other technical fields and titles; institutions and communities were founded, and unprecedented applications to and interactions with other aspects of society and culture occurred. The term scientist was coined by the naturalist-theologian William Whewell in 1834 and it was applied to those who sought knowledge and understanding of nature. From the ancient world, starting with Aristotle, to the 19th century, the practice of studying nature was commonly referred to as "natural philosophy". Isaac Newton's book Philosophiae Naturalis Principia Mathematica (1687), whose title translates to "Mathematical Principles of Natural Philosophy", reflects the then-current use of the words "natural philosophy", akin to "systematic study of nature". Even in the 19th century, a treatise by Lord Kelvin and Peter Guthrie Tait's, which helped define much of modern physics, was titled Treatise on Natural Philosophy (1867).
It was in the 17th century that the concept of "religion" received its modern shape despite the fact that ancient texts like the Bible, the Quran, and other texts did not have a concept of religion in the original languages and neither did the people or the cultures in which these texts were written. In the 19th century, Max Müller noted that what is called ancient religion today, would have been called "law" in antiquity. For example, there is no precise equivalent of "religion" in Hebrew, and Judaism does not distinguish clearly between religious, national, racial, or ethnic identities. The Sanskrit word "dharma", sometimes translated as "religion", also means law or duty. Throughout classical India, the study of law consisted of concepts such as penance through piety and ceremonial as well as practical traditions. Medieval Japan at first had a similar union between "imperial law" and universal or "Buddha law", but these later became independent sources of power. Throughout its long history, Japan had no concept of "religion" since there was no corresponding Japanese word, nor anything close to its meaning, but when American warships appeared off the coast of Japan in 1853 and forced the Japanese government to sign treaties demanding, among other things, freedom of religion, the country had to contend with this Western idea.
=== Middle Ages and Renaissance ===
The development of sciences (especially natural philosophy) in Western Europe during the Middle Ages, has a considerable foundation in the works of the Arabs who translated Greek and Latin compositions. The works of Aristotle played a major role in the institutionalization, systematization, and expansion of reason. Christianity accepted reason within the ambit of faith. In Christendom, ideas articulated via divine revelation were assumed to be true, and thus via the law of non-contradiction, it was maintained that the natural world must accord with this revealed truth. Any apparent contradiction would indicate either a misunderstanding of the natural world or a misunderstanding of revelation. The prominent scholastic Thomas Aquinas writes in the Summa Theologica concerning apparent contradictions:
"In discussing questions of this kind two rules are to observed, as Augustine teaches (Gen. ad lit. i, 18). The first is, to hold the truth of Scripture without wavering. The second is that since Holy Scripture can be explained in a multiplicity of senses, one should adhere to a particular explanation, only in such measure as to be ready to abandon it, if it be proved with certainty to be false; lest Holy Scripture be exposed to the ridicule of unbelievers, and obstacles be placed to their believing." (Summa 1a, 68, 1)
where the referenced text from Augustine of Hippo reads:
"In matters that are obscure and far beyond our vision, even in such as we may find treated in Holy Scripture, different interpretations are sometimes possible without prejudice to the faith we have received. In such a case, we should not rush in headlong and so firmly take our stand on one side that, if further progress in the search of truth justly undermines this position, we too fall with it. That would be to battle not for the teaching of Holy Scripture but for our own, wishing its teaching to conform to ours, whereas we ought to wish ours to conform to that of Sacred Scripture." (Gen. ad lit. i, 18)
In medieval universities, the faculty for natural philosophy and theology were separate, and discussions pertaining to theological issues were often not allowed to be undertaken by the faculty of philosophy. Natural philosophy, as taught in the arts faculties of the universities, was seen as an essential area of study in its own right and was considered necessary for almost every area of study. It was an independent field, separated from theology, and enjoyed a good deal of intellectual freedom as long as it was restricted to the natural world. In general, there was religious support for natural science by the late Middle Ages and a recognition that it was an important element of learning.
The extent to which medieval science led directly to the new philosophy of the scientific revolution remains a subject for debate, but it certainly had a significant influence.
The Middle Ages laid ground for the developments that took place in science, during the Renaissance which immediately succeeded it. By 1630, ancient authority from classical literature and philosophy, as well as their necessity, started eroding, although scientists were still expected to be fluent in Latin, the international language of Europe's intellectuals. With the sheer success of science and the steady advance of rationalism, the individual scientist gained prestige. Along with the inventions of this period, especially the printing press by Johannes Gutenberg, allowing for the dissemination of the Bible in vernacular languages. This allowed more people to read and learn from the scripture, leading to the Evangelical movement. The people who spread this message concentrated more on individual agency rather than the structures of the Church.
==== Medieval Contributors ====
Some medieval contributors to science included: Boethius (c. 477–524), John Philoponus (c. 490–570), Bede the Venerable (c. 672–735), Alcuin of York (c. 735–804), Leo the Mathematician (c. 790–869), Gerbert of Aurillac (c. 946–1003), Constantine the African (c. 1020–1087), Adelard of Bath (c. 1080–1152), Robert Grosseteste (c. 1168–1253), St. Albert the Great (c. 1200–1280), Roger Bacon (c. 1214–1294), William of Ockham (c. 1287–1347), Jean Burdian (c. 1301–1358), Thomas Bradwardine (1300–1349), Nicole Oresme (c. 1320–1382), Nicholas of Cusa (c. 1401–1464).
=== Modern period ===
In the 17th century, founders of the Royal Society largely held conventional and orthodox religious views, and a number of them were prominent Churchmen. While theological issues that had the potential to be divisive were typically excluded from formal discussions of the early Society, many of its fellows nonetheless believed that their scientific activities provided support for traditional religious belief. Clerical involvement in the Royal Society remained high until the mid-nineteenth century when science became more professionalized.
Albert Einstein supported the compatibility of some interpretations of religion with science. In "Science, Philosophy and Religion, A Symposium" published by the Conference on Science, Philosophy and Religion in Their Relation to the Democratic Way of Life, Inc., New York in 1941, Einstein stated:
Accordingly, a religious person is devout in the sense that he has no doubt of the significance and loftiness of those superpersonal objects and goals which neither require nor are capable of rational foundation. They exist with the same necessity and matter-of-factness as he himself. In this sense religion is the age-old endeavor of mankind to become clearly and completely conscious of these values and goals and constantly to strengthen and extend their effect. If one conceives of religion and science according to these definitions then a conflict between them appears impossible. For science can only ascertain what is, but not what should be, and outside of its domain value judgments of all kinds remain necessary. Religion, on the other hand, deals only with evaluations of human thought and action: it cannot justifiably speak of facts and relationships between facts. According to this interpretation the well-known conflicts between religion and science in the past must all be ascribed to a misapprehension of the situation which has been described.
Einstein thus expresses views of ethical non-naturalism (contrasted to ethical naturalism).
Prominent modern scientists who are atheists include evolutionary biologist Richard Dawkins and Nobel Prize–winning physicist Steven Weinberg. Prominent scientists advocating religious belief include Nobel Prize–winning physicist and United Church of Christ member Charles Townes, evangelical Christian and past head of the Human Genome Project Francis Collins, and climatologist John T. Houghton.
== Perspectives ==
The kinds of interactions that might arise between science and religion have been categorized by theologian, Anglican priest, and physicist John Polkinghorne: (1) conflict between the disciplines, (2) independence of the disciplines, (3) dialogue between the disciplines where they overlap and (4) integration of both into one field.
This typology is similar to ones used by theologians Ian Barbour and John Haught. More typologies that categorize this relationship can be found among the works of other science and religion scholars such as theologian and biochemist Arthur Peacocke.
=== Incompatibility ===
According to Guillermo Paz-y-Miño-C and Avelina Espinosa, the historical conflict between evolution and religion is intrinsic to the incompatibility between scientific rationalism/empiricism and the belief in supernatural causation/faith. According to evolutionary biologist Jerry Coyne, views on evolution and levels of religiosity in some countries, along with the existence of books explaining reconciliation between evolution and religion, indicate that people have trouble in believing both at the same time, thus implying incompatibility. According to physical chemist Peter Atkins, "whereas religion scorns the power of human comprehension, science respects it." Planetary scientist Carolyn Porco describes a hope that "the confrontation between science and formal religion will come to an end when the role played by science in the lives of all people is the same played by religion today."
Geologist and paleontologist Donald Prothero has stated that religion is the reason "questions about evolution, the age of the earth, cosmology, and human evolution nearly always cause Americans to flunk science literacy tests compared to other nations." However, Jon Miller, who studies science literacy across nations, states that Americans in general are slightly more scientifically literate than Europeans and the Japanese.
According to cosmologist and astrophysicist Lawrence Krauss, compatibility or incompatibility is a theological concern, not a scientific concern. In Lisa Randall's view, questions of incompatibility or otherwise are not answerable, since by accepting revelations one is abandoning rules of logic which are needed to identify if there are indeed contradictions between holding certain beliefs. Daniel Dennett holds that incompatibility exists because religion is not problematic to a certain point before it collapses into a number of excuses for keeping certain beliefs, in light of evolutionary implications.
According to theoretical physicist Steven Weinberg, teaching cosmology and evolution to students should decrease their self-importance in the universe, as well as their religiosity. Evolutionary developmental biologist PZ Myers' view is that all scientists should be atheists, and that science should never accommodate any religious beliefs. Physicist Sean M. Carroll claims that since religion makes claims that are supernatural, both science and religion are incompatible.
Evolutionary biologist Richard Dawkins is openly hostile to religion because he believes it actively debauches the scientific enterprise and education involving science. According to Dawkins, religion "subverts science and saps the intellect". He believes that when science teachers attempt to expound on evolution, there is hostility aimed towards them by parents who are skeptical because they believe it conflicts with their own religious beliefs, and that even in some textbooks have had the word 'evolution' systematically removed. He has worked to argue the negative effects that he believes religion has on education of science.
According to Renny Thomas' study on Indian scientists, atheistic scientists in India called themselves atheists even while accepting that their lifestyle is very much a part of tradition and religion. Thus, they differ from Western atheists in that for them following the lifestyle of a religion is not antithetical to atheism.
==== Criticism ====
Others such as Francis Collins, George F. R. Ellis, Kenneth R. Miller, Katharine Hayhoe, George Coyne and Simon Conway Morris argue for compatibility since they do not agree that science is incompatible with religion and vice versa. They argue that science provides many opportunities to look for and find God in nature and to reflect on their beliefs. According to Kenneth Miller, he disagrees with Jerry Coyne's assessment and argues that since significant portions of scientists are religious and the proportion of Americans believing in evolution is much higher, it implies that both are indeed compatible. Elsewhere, Miller has argued that when scientists make claims on science and theism or atheism, they are not arguing scientifically at all and are stepping beyond the scope of science into discourses of meaning and purpose. What he finds particularly odd and unjustified is in how atheists often come to invoke scientific authority on their non-scientific philosophical conclusions like there being no point or no meaning to the universe as the only viable option when the scientific method and science never have had any way of addressing questions of meaning or God in the first place. Furthermore, he notes that since evolution made the brain and since the brain can handle both religion and science, there is no natural incompatibility between the concepts at the biological level.
Karl Giberson argues that when discussing compatibility, some scientific intellectuals often ignore the viewpoints of intellectual leaders in theology and instead argue against less informed masses, thereby, defining religion by non-intellectuals and slanting the debate unjustly. He argues that leaders in science sometimes trump older scientific baggage and that leaders in theology do the same, so once theological intellectuals are taken into account, people who represent extreme positions like Ken Ham and Eugenie Scott will become irrelevant. Cynthia Tolman notes that religion does not have a method per se partly because religions emerge through time from diverse cultures, but when it comes to Christian theology and ultimate truths, she notes that people often rely on scripture, tradition, reason, and experience to test and gauge what they experience and what they should believe.
==== Conflict thesis ====
The conflict thesis, which holds that religion and science have been in conflict continuously throughout history, was popularized in the 19th century by John William Draper's and Andrew Dickson White's accounts. It was in the 19th century that relationship between science and religion became an actual formal topic of discourse, while before this no one had pitted science against religion or vice versa, though occasional complex interactions had been expressed before the 19th century. Most contemporary historians of science now reject the conflict thesis in its original form and no longer support it. Instead, it has been superseded by subsequent historical research which has resulted in a more nuanced understanding. Historian of science, Gary Ferngren, has stated: "Although popular images of controversy continue to exemplify the supposed hostility of Christianity to new scientific theories, studies have shown that Christianity has often nurtured and encouraged scientific endeavour, while at other times the two have co-existed without either tension or attempts at harmonization. If Galileo and the Scopes trial come to mind as examples of conflict, they were the exceptions rather than the rule."
Most historians today have moved away from a conflict model, which is based mainly on two historical episodes (Galileo and Darwin), toward compatibility theses (either the integration thesis or non-overlapping magisteria) or toward a "complexity" model, because religious figures were on both sides of each dispute and there was no overall aim by any party involved to discredit religion.
An often cited example of conflict, that has been clarified by historical research in the 20th century, was the Galileo affair, whereby interpretations of the Bible were used to attack ideas by Copernicus on heliocentrism. By 1616 Galileo went to Rome to try to persuade Catholic Church authorities not to ban Copernicus' ideas. In the end, a decree of the Congregation of the Index was issued, declaring that the ideas that the Sun stood still and that the Earth moved were "false" and "altogether contrary to Holy Scripture", and suspending Copernicus's De Revolutionibus until it could be corrected. Galileo was found "vehemently suspect of heresy", namely of having held the opinions that the Sun lies motionless at the center of the universe, that the Earth is not at its centre and moves. He was required to "abjure, curse and detest" those opinions. However, before all this, Pope Urban VIII had personally asked Galileo to give arguments for and against heliocentrism in a book, and to be careful not to advocate heliocentrism as physically proven since the scientific consensus at the time was that the evidence for heliocentrism was very weak. The Church had merely sided with the scientific consensus of the time. Pope Urban VIII asked that his own views on the matter be included in Galileo's book. Only the latter was fulfilled by Galileo. Whether unknowingly or deliberately, Simplicio, the defender of the Aristotelian/Ptolemaic geocentric view in Dialogue Concerning the Two Chief World Systems, was often portrayed as an unlearned fool who lacked mathematical training. Although the preface of his book claims that the character is named after a famous Aristotelian philosopher (Simplicius in Latin, Simplicio in Italian), the name "Simplicio" in Italian also has the connotation of "simpleton". Unfortunately for his relationship with the Pope, Galileo put the words of Urban VIII into the mouth of Simplicio. Most historians agree Galileo did not act out of malice and felt blindsided by the reaction to his book. However, the Pope did not take the suspected public ridicule lightly, nor the physical Copernican advocacy. Galileo had alienated one of his biggest and most powerful supporters, the Pope, and was called to Rome to defend his writings.
The actual evidences that finally proved heliocentrism came centuries after Galileo: the stellar aberration of light by James Bradley in the 18th century, the orbital motions of binary stars by William Herschel in the 19th century, the accurate measurement of the stellar parallax in the 19th century, and Newtonian mechanics in the 17th century. According to physicist Christopher Graney, Galileo's own observations did not actually support the Copernican view, but were more consistent with Tycho Brahe's hybrid model where that Earth did not move and everything else circled around it and the Sun.
British philosopher A. C. Grayling, still believes there is competition between science and religions in areas related to the origin of the universe, the nature of human beings and the possibility of miracles.
=== Independence ===
A modern view, described by Stephen Jay Gould as "non-overlapping magisteria" (NOMA), is that science and religion deal with fundamentally separate aspects of human experience and so, when each stays within its own domain, they co-exist peacefully. While Gould spoke of independence from the perspective of science, W. T. Stace viewed independence from the perspective of the philosophy of religion. Stace felt that science and religion, when each is viewed in its own domain, are both consistent and complete. They originate from different perceptions of reality, as Arnold O. Benz points out, but meet each other, for example, in the feeling of amazement and in ethics.
The USA's National Academy of Sciences supports the view that science and religion are independent.
Science and religion are based on different aspects of human experience. In science, explanations must be based on evidence drawn from examining the natural world. Scientifically based observations or experiments that conflict with an explanation eventually must lead to modification or even abandonment of that explanation. Religious faith, in contrast, does not depend on empirical evidence, is not necessarily modified in the face of conflicting evidence, and typically involves supernatural forces or entities. Because they are not a part of nature, supernatural entities cannot be investigated by science. In this sense, science and religion are separate and address aspects of human understanding in different ways. Attempts to put science and religion against each other create controversy where none needs to exist.
According to Archbishop John Habgood, both science and religion represent distinct ways of approaching experience and these differences are sources of debate. He views science as descriptive and religion as prescriptive. He stated that if science and mathematics concentrate on what the world ought to be, in the way that religion does, it may lead to improperly ascribing properties to the natural world as happened among the followers of Pythagoras in the sixth century B.C. In contrast, proponents of a normative moral science take issue with the idea that science has no way of guiding "oughts". Habgood also stated that he believed that the reverse situation, where religion attempts to be descriptive, can also lead to inappropriately assigning properties to the natural world. A notable example is the now defunct belief in the Ptolemaic (geocentric) planetary model that held sway until changes in scientific and religious thinking were brought about by Galileo and proponents of his views.
In the view of the Lubavitcher rabbi Menachem Mendel Schneerson, non-Euclidean geometry such as Lobachevsky's hyperbolic geometry and Riemann's elliptic geometry proved that Euclid's axioms, such as, "there is only one straight line between two points", are in fact arbitrary. Therefore, science, which relies on arbitrary axioms, can never refute Torah, which is absolute truth.
==== Parallels in method ====
According to Ian Barbour, Thomas S. Kuhn asserted that science is made up of paradigms that arise from cultural traditions, which is similar to the secular perspective on religion.
Michael Polanyi asserted that it is merely a commitment to universality that protects against subjectivity and has nothing at all to do with personal detachment as found in many conceptions of the scientific method. Polanyi further asserted that all knowledge is personal and therefore the scientist must be performing a very personal if not necessarily subjective role when doing science. Polanyi added that the scientist often merely follows intuitions of "intellectual beauty, symmetry, and 'empirical agreement'". Polanyi held that science requires moral commitments similar to those found in religion.
Two physicists, Charles A. Coulson and Harold K. Schilling, both claimed that "the methods of science and religion have much in common." Schilling asserted that both fields—science and religion—have "a threefold structure—of experience, theoretical interpretation, and practical application." Coulson asserted that science, like religion, "advances by creative imagination" and not by "mere collecting of facts," while stating that religion should and does "involve critical reflection on experience not unlike that which goes on in science." Religious language and scientific language also show parallels (cf. rhetoric of science).
=== Dialogue ===
The religion and science community consists of those scholars who involve themselves with what has been called the "religion-and-science dialogue" or the "religion-and-science field." The community belongs to neither the scientific nor the religious community, but is said to be a third overlapping community of interested and involved scientists, priests, clergymen, theologians and engaged non-professionals. Institutions interested in the intersection between science and religion include the Center for Theology and the Natural Sciences, the Institute on Religion in an Age of Science, the Ian Ramsey Centre, and the Faraday Institute. Journals addressing the relationship between science and religion include Theology and Science and Zygon. Eugenie Scott has written that the "science and religion" movement is, overall, composed mainly of theists who have a healthy respect for science and may be beneficial to the public understanding of science. She contends that the "Christian scholarship" movement is not a problem for science, but that the "Theistic science" movement, which proposes abandoning methodological materialism, does cause problems in understanding of the nature of science. The Gifford Lectures were established in 1885 to further the discussion between "natural theology" and the scientific community. This annual series continues and has included William James, John Dewey, Carl Sagan, and many other professors from various fields.
The modern dialogue between religion and science is rooted in Ian Barbour's 1966 book Issues in Science and Religion. Since that time it has grown into a serious academic field, with academic chairs in the subject area, and two dedicated academic journals, Zygon and Theology and Science. Articles are also sometimes found in mainstream science journals such as American Journal of Physics
and Science.
Philosopher Alvin Plantinga has argued that there is superficial conflict but deep concord between science and religion, and that there is deep conflict between science and naturalism. Plantinga, in his book Where the Conflict Really Lies: Science, Religion, and Naturalism, heavily contests the linkage of naturalism with science, as conceived by Richard Dawkins, Daniel Dennett and like-minded thinkers; while Daniel Dennett thinks that Plantinga stretches science to an unacceptable extent. Philosopher Maarten Boudry, in reviewing the book, has commented that he resorts to creationism and fails to "stave off the conflict between theism and evolution." Cognitive scientist Justin L. Barrett, by contrast, reviews the same book and writes that "those most needing to hear Plantinga's message may fail to give it a fair hearing for rhetorical rather than analytical reasons."
=== Integration ===
As a general view, this holds that while interactions are complex between influences of science, theology, politics, social, and economic concerns, the productive engagements between science and religion throughout history should be duly stressed as the norm.
Scientific and theological perspectives often coexist peacefully. Christians and some non-Christian religions have historically integrated well with scientific ideas, as in the ancient Egyptian technological mastery applied to monotheistic ends, the scientific advances made by Muslim scholars during the Ottoman Empire and mathematics under Hinduism and Buddhism. Even many 19th-century Christian communities welcomed scientists who claimed that science was not at all concerned with discovering the ultimate nature of reality. According to Lawrence M. Principe, the Johns Hopkins University Drew Professor of the Humanities, from a historical perspective this points out that much of the current-day clashes occur between limited extremists—both religious and scientistic fundamentalists—over a very few topics, and that the movement of ideas back and forth between scientific and theological thought has been more usual. To Principe, this perspective would point to the fundamentally common respect for written learning in religious traditions of rabbinical literature, Christian theology, and the Islamic Golden Age, including a Transmission of the Classics from Greek to Islamic to Christian traditions which helped spark the Renaissance. Religions have also given key participation in development of modern universities and libraries; centers of learning & scholarship were coincident with religious institutions—whether pagan, Muslim, or Christian.
== Individual religions ==
=== Baháʼí Faith ===
A fundamental principle of the Baháʼí Faith is the harmony of religion and science. Baháʼí scripture asserts that true science and true religion can never be in conflict. `Abdu'l-Bahá, the son of the founder of the religion, stated that religion without science is superstition and that science without religion is materialism. He also admonished that true religion must conform to the conclusions of science.
=== Buddhism ===
Buddhism and science have been regarded as compatible by numerous authors. Some philosophic and psychological teachings found in Buddhism share points in common with modern Western scientific and philosophic thought. For example, Buddhism encourages the impartial investigation of nature (an activity referred to as Dhamma-Vicaya in the Pali Canon)—the principal object of study being oneself. Buddhism and science both show a strong emphasis on causality. However, Buddhism does not focus on materialism.
Tenzin Gyatso, the 14th Dalai Lama, mentions that empirical scientific evidence supersedes the traditional teachings of Buddhism when the two are in conflict. In his book The Universe in a Single Atom he wrote, "My confidence in venturing into science lies in my basic belief that as in science, so in Buddhism, understanding the nature of reality is pursued by means of critical investigation." He also stated, "If scientific analysis were conclusively to demonstrate certain claims in Buddhism to be false," he says, "then we must accept the findings of science and abandon those claims."
=== Christianity ===
Among early Christian teachers, Tertullian (c. 160–220) held a generally negative opinion of Greek philosophy, while Origen (c. 185–254) regarded it much more favorably and required his students to read nearly every work available to them.
Earlier attempts at reconciliation of Christianity with Newtonian mechanics appear quite different from later attempts at reconciliation with the newer scientific ideas of evolution or relativity. Many early interpretations of evolution polarized themselves around a struggle for existence. These ideas were significantly countered by later findings of universal patterns of biological cooperation. According to John Habgood, the universe seems to be a mix of good and evil, beauty and pain, and that suffering may somehow be part of the process of creation. Habgood holds that Christians should not be surprised that suffering may be used creatively by God, given their faith in the symbol of the Cross.
Robert John Russell has examined consonance and dissonance between modern physics, evolutionary biology, and Christian theology.
Christian philosophers Augustine of Hippo (354–430) and Thomas Aquinas (1225–1274) held that scriptures can have multiple interpretations on certain areas where the matters were far beyond their reach, therefore one should leave room for future findings to shed light on the meanings. The "Handmaiden" tradition, which saw secular studies of the universe as a very important and helpful part of arriving at a better understanding of scripture, was adopted throughout Christian history from early on. Also the sense that God created the world as a self operating system is what motivated many Christians throughout the Middle Ages to investigate nature.
Modern historians of science such as J.L. Heilbron, Alistair Cameron Crombie, David Lindberg, Edward Grant, Thomas Goldstein, and Ted Davis have reviewed the popular notion that medieval Christianity was a negative influence in the development of civilization and science. In their views, not only did the monks save and cultivate the remnants of ancient civilization during the barbarian invasions, but the medieval church promoted learning and science through its sponsorship of many universities which, under its leadership, grew rapidly in Europe in the 11th and 12th centuries. Saint Thomas Aquinas, the Church's "model theologian", not only argued that reason is in harmony with faith, he even recognized that reason can contribute to understanding revelation, and so encouraged intellectual development. He was not unlike other medieval theologians who sought out reason in the effort to defend his faith. Some modern scholars, such as Stanley Jaki, have claimed that Christianity with its particular worldview, was a crucial factor for the emergence of modern science.
David C. Lindberg states that the widespread popular belief that the Middle Ages was a time of ignorance and superstition due to the Christian church is a "caricature". According to Lindberg, while there are some portions of the classical tradition which suggest this view, these were exceptional cases. It was common to tolerate and encourage critical thinking about the nature of the world. The relation between Christianity and science is complex and cannot be simplified to either harmony or conflict, according to Lindberg. Lindberg reports that "the late medieval scholar rarely experienced the coercive power of the church and would have regarded himself as free (particularly in the natural sciences) to follow reason and observation wherever they led. There was no warfare between science and the church." Ted Peters in Encyclopedia of Religion writes that although there is some truth in the "Galileo's condemnation" story but through exaggerations, it has now become "a modern myth perpetuated by those wishing to see warfare between science and religion who were allegedly persecuted by an atavistic and dogma-bound ecclesiastical authority". In 1992, the Catholic Church's seeming vindication of Galileo attracted much comment in the media.
A degree of concord between science and religion can be seen in religious belief and empirical science. The belief that God created the world and therefore humans, can lead to the view that he arranged for humans to know the world. This is underwritten by the doctrine of imago dei. In the words of Thomas Aquinas, "Since human beings are said to be in the image of God in virtue of their having a nature that includes an intellect, such a nature is most in the image of God in virtue of being most able to imitate God".
During the Enlightenment, a period "characterized by dramatic revolutions in science" and the rise of Protestant challenges to the authority of the Catholic Church via individual liberty, the authority of Christian scriptures became strongly challenged. As science advanced, acceptance of a literal version of the Bible became "increasingly untenable" and some in that period presented ways of interpreting scripture according to its spirit on its authority and truth.
After the Black Death in Europe, there occurred a generalized decrease in faith in the Catholic Church. The "Natural Sciences" during the Medieval Era focused largely on scientific arguments. The Copernicans, who were generally a small group of privately sponsored individuals, who were deemed Heretics by the Church in some instances. Copernicus and his work challenged the view held by the Catholic Church and the common scientific view at the time, yet according to scholar J. L. Heilbron, the Roman Catholic Church sometimes provided financial support to the Copernicans. In doing so, the Church did support and promote scientific research when the goals in question were in alignment with those of the faith, so long as the findings were in line with the rhetoric of the Church. A case example is the Catholic need for an accurate calendar. Calendar reform was a touchy subject: civilians doubted the accuracy of the mathematics and were upset that the process unfairly selected curators of the reform. The Roman Catholic Church needed a precise date for the Easter Sabbath, and thus the Church was highly supportive of calendar reform. The need for the correct date of Easter was also the impetus of cathedral construction. Cathedrals essentially functioned as massive scale sun dials and, in some cases, camera obscuras. They were efficient scientific devices because they rose high enough for their naves to determine the summer and winter solstices. Heilbron contends that as far back as the twelfth century, the Roman Catholic Church was funding scientific discovery and the recovery of ancient Greek scientific texts. However, the Copernican revolution challenged the view held the Catholic Church and placed the Sun at the center of the Solar System.
==== Perspectives on evolution ====
In recent history, the theory of evolution has been at the center of some controversy between Christianity and science. Christians who accept a literal interpretation of the biblical account of creation find incompatibility between Darwinian evolution and their interpretation of the Christian faith. Creation science or scientific creationism is a branch of creationism that attempts to provide scientific support for a literal reading of the Genesis creation narrative in the Book of Genesis and attempts to disprove generally accepted scientific facts, theories and scientific paradigms about the geological history of the Earth, cosmology of the early universe,
the chemical origins of life and biological evolution. It began in the 1960s as a fundamentalist Christian effort in the United States to prove Biblical inerrancy and falsify the scientific evidence for evolution. It has since developed a sizable religious following in the United States, with creation science ministries branching worldwide. In 1925, The State of Tennessee passed the Butler Act, which prohibited the teaching of the theory of evolution in all schools in the state. Later that year, a similar law was passed in Mississippi, and likewise, Arkansas in 1927. In 1968, these "anti-monkey" laws were struck down by the Supreme Court of the United States as unconstitutional, "because they established a religious doctrine violating both the First and Fourth Amendments to the Constitution."
Most scientists have rejected creation science for several reasons, including that its claims do not refer to natural causes and cannot be tested. In 1987, the United States Supreme Court ruled that creationism is religion, not science, and cannot be advocated in public school classrooms. In 2018, the Orlando Sentinel reported that "Some private schools in Florida that rely on public funding teach students" Creationism.
Theistic evolution attempts to reconcile Christian beliefs and science by accepting the scientific understanding of the age of the Earth and the process of evolution. It includes a range of beliefs, including views described as evolutionary creationism, which accepts some findings of modern science but also upholds classical religious teachings about God and creation in Christian context.
==== Roman Catholicism ====
While refined and clarified over the centuries, the Roman Catholic position on the relationship between science and religion is one of harmony, and has maintained the teaching of natural law as set forth by Thomas Aquinas. For example, regarding scientific study such as that of evolution, the church's unofficial position is an example of theistic evolution, stating that faith and scientific findings regarding human evolution are not in conflict, though humans are regarded as a special creation, and that the existence of God is required to explain both monogenism and the spiritual component of human origins. Catholic schools have included all manners of scientific study in their curriculum for many centuries.
Galileo once stated that "The intention of the Holy Spirit is to teach us how to go to heaven, not how the heavens go." In 1981, Pope John Paul II, then leader of the Roman Catholic Church, spoke of the relationship this way: "The Bible itself speaks to us of the origin of the universe and its make-up, not in order to provide us with a scientific treatise, but in order to state the correct relationships of man with God and with the universe. Sacred Scripture wishes simply to declare that the world was created by God, and in order to teach this truth it expresses itself in the terms of the cosmology in use at the time of the writer".
Pope Francis, in his encyclical letter Laudato si', affirms his opinion that "science and religion, with their distinctive approaches to understanding reality, can
enter into an intense dialogue fruitful for both".
==== Influence of a biblical worldview on early modern science ====
According to Andrew Dickson White's A History of the Warfare of Science with Theology in Christendom from the 19th century, a biblical world view affected negatively the progress of science through time. Dickinson also argues that immediately following the Reformation matters were even worse. The interpretations of Scripture by Luther and Calvin became as sacred to their followers as the Scripture itself. For instance, when Georg Calixtus ventured, in interpreting the Psalms, to question the accepted belief that "the waters above the heavens" were contained in a vast receptacle upheld by a solid vault, he was bitterly denounced as heretical. Today, much of the scholarship in which the conflict thesis was originally based is considered to be inaccurate. For instance, the claim that early Christians rejected scientific findings by the Greco-Romans is false, since the "handmaiden" view of secular studies was seen to shed light on theology. This view was widely adapted throughout the early medieval period and afterwards by theologians (such as Augustine) and ultimately resulted in fostering interest in knowledge about nature through time. Also, the claim that people of the Middle Ages widely believed that the Earth was flat was first propagated in the same period that originated the conflict thesis and is still very common in popular culture. Modern scholars regard this claim as mistaken, as the contemporary historians of science David C. Lindberg and Ronald L. Numbers write: "there was scarcely a Christian scholar of the Middle Ages who did not acknowledge [earth's] sphericity and even know its approximate circumference." From the fall of Rome to the time of Columbus, all major scholars and many vernacular writers interested in the physical shape of the earth held a spherical view with the exception of Lactantius and Cosmas.
H. Floris Cohen argued for a biblical Protestant, but not excluding Catholicism, influence on the early development of modern science. He presented Dutch historian R. Hooykaas' argument that a biblical world-view holds all the necessary antidotes for the hubris of Greek rationalism: a respect for manual labour, leading to more experimentation and empiricism, and a supreme God that left nature open to emulation and manipulation. It supports the idea early modern science rose due to a combination of Greek and biblical thought.
Oxford historian Peter Harrison is another who has argued that a biblical worldview was significant for the development of modern science. Harrison contends that Protestant approaches to the book of scripture had significant, if largely unintended, consequences for the interpretation of the book of nature. Harrison has also suggested that literal readings of the Genesis narratives of the Creation and Fall motivated and legitimated scientific activity in seventeenth-century England. For many of its seventeenth-century practitioners, science was imagined to be a means of restoring a human dominion over nature that had been lost as a consequence of the Fall.
Historian and professor of religion Eugene M. Klaaren holds that "a belief in divine creation" was central to an emergence of science in seventeenth-century England. The philosopher Michael Foster has published analytical philosophy connecting Christian doctrines of creation with empiricism. Historian William B. Ashworth has argued against the historical notion of distinctive mind-sets and the idea of Catholic and Protestant sciences. Historians James R. Jacob and Margaret C. Jacob have argued for a linkage between seventeenth-century Anglican intellectual transformations and influential English scientists (e.g., Robert Boyle and Isaac Newton). John Dillenberger and Christopher B. Kaiser have written theological surveys, which also cover additional interactions occurring in the 18th, 19th, and 20th centuries. Philosopher of Religion, Richard Jones, has written a philosophical critique of the "dependency thesis" which assumes that modern science emerged from Christian sources and doctrines. Though he acknowledges that modern science emerged in a religious framework, that Christianity greatly elevated the importance of science by sanctioning and religiously legitimizing it in the medieval period, and that Christianity created a favorable social context for it to grow; he argues that direct Christian beliefs or doctrines were not primary sources of scientific pursuits by natural philosophers, nor was Christianity, in and of itself, exclusively or directly necessary in developing or practicing modern science.
Oxford University historian and theologian John Hedley Brooke wrote that "when natural philosophers referred to laws of nature, they were not glibly choosing that metaphor. Laws were the result of legislation by an intelligent deity. Thus the philosopher René Descartes (1596–1650) insisted that he was discovering the "laws that God has put into nature." Later Newton would declare that the regulation of the solar system presupposed the "counsel and dominion of an intelligent and powerful Being." Historian Ronald L. Numbers stated that this thesis "received a boost" from mathematician and philosopher Alfred North Whitehead's Science and the Modern World (1925). Numbers has also argued, "Despite the manifest shortcomings of the claim that Christianity gave birth to science—most glaringly, it ignores or minimizes the contributions of ancient Greeks and medieval Muslims—it too, refuses to succumb to the death it deserves." The sociologist Rodney Stark of Baylor University, argued in contrast that "Christian theology was essential for the rise of science."
Protestantism had an important influence on science. According to the Merton Thesis there was a positive correlation between the rise of Puritanism and Protestant Pietism on the one hand and early experimental science on the other. The Merton Thesis has two separate parts: Firstly, it presents a theory that science changes due to an accumulation of observations and improvement in experimental techniques and methodology; secondly, it puts forward the argument that the popularity of science in 17th-century England and the religious demography of the Royal Society (English scientists of that time were predominantly Puritans or other Protestants) can be explained by a correlation between Protestantism and the scientific values. In his theory, Robert K. Merton focused on English Puritanism and German Pietism as having been responsible for the development of the scientific revolution of the 17th and 18th centuries. Merton explained that the connection between religious affiliation and interest in science was the result of a significant synergy between the ascetic Protestant values and those of modern science. Protestant values encouraged scientific research by allowing science to study God's influence on the world and thus providing a religious justification for scientific research.
Some scholars have noted a direct tie between "particular aspects of traditional Christianity" and the rise of science. Other scholars and historians attribute Christianity to having contributed to the rise of the Scientific Revolution.
==== Reconciliation in Britain in the early 20th century ====
In Reconciling Science and Religion: The Debate in Early-twentieth-century Britain, historian of biology Peter J. Bowler argues that in contrast to the conflicts between science and religion in the U.S. in the 1920s (most famously the Scopes Trial), during this period Great Britain experienced a concerted effort at reconciliation, championed by intellectually conservative scientists, supported by liberal theologians but opposed by younger scientists and secularists and conservative Christians. These attempts at reconciliation fell apart in the 1930s due to increased social tensions, moves towards neo-orthodox theology and the acceptance of the modern evolutionary synthesis.
In the 20th century, several ecumenical organizations promoting a harmony between science and Christianity were founded, most notably the American Scientific Affiliation, The Biologos Foundation, Christians in Science, The Society of Ordained Scientists, and The Veritas Forum.
=== Confucianism and traditional Chinese religion ===
The historical process of Confucianism has largely been antipathic towards scientific discovery. However the religio-philosophical system itself is more neutral on the subject than such an analysis might suggest. In his writings On Heaven, Xunzi espoused a proto-scientific world view. However, during the Han Synthesis the more anti-empirical Mencius was favored and combined with Daoist skepticism regarding the nature of reality. Likewise, during the medieval period, Zhu Xi argued against technical investigation and specialization proposed by Chen Liang. After contact with the West, scholars such as Wang Fuzhi would rely on Buddhist/Daoist skepticism to denounce all science as a subjective pursuit limited by humanity's fundamental ignorance of the true nature of the world.
The Jesuits from Europe taught Western math and science to the Chinese bureaucrats in hopes of religious conversion. This process saw several challenges of both European and Chinese spiritual and scientific beliefs. The keynote text of Chinese scientific philosophy, The Book of Changes (or Yi Jing) was initially mocked and disregarded by the Westerners. In return, Confucian scholars Dai Zhen and Ji Yun found the concept of phantoms laughable and ridiculous. The Book of Changes outlined orthodoxy cosmology in the Qing, including yin and yang and the five cosmic phases. Sometimes the missionary exploits proved dangerous for the Westerners. Jesuit missionaries and scholars Ferdinand Vervbiest and Adam Schall were punished after using scientific methods to determine the exact time of the 1664 eclipse. However, the European mission eastward did not only cause conflict. Joachim Bouvet, a theologian who held equal respect for both the Bible and the Book of Changes, was productive in his mission of spreading the Christian faith.
After the May Fourth Movement, attempts to modernize Confucianism and reconcile it with scientific understanding were attempted by many scholars including Feng Youlan and Xiong Shili. Given the close relationship that Confucianism shares with Buddhism, many of the same arguments used to reconcile Buddhism with science also readily translate to Confucianism. However, modern scholars have also attempted to define the relationship between science and Confucianism on Confucianism's own terms and the results have usually led to the conclusion that Confucianism and science are fundamentally compatible.
=== Hinduism ===
In Hinduism, the dividing line between objective sciences and spiritual knowledge (adhyatma vidya) is a linguistic paradox. Hindu scholastic activities and ancient Indian scientific advancements were so interconnected that many Hindu scriptures are also ancient scientific manuals and vice versa. In 1835, English was made the primary language for teaching in higher education in India, exposing Hindu scholars to Western secular ideas; this started a renaissance regarding religious and philosophical thought. Hindu sages maintained that logical argument and rational proof using Nyaya is the way to obtain correct knowledge. The scientific level of understanding focuses on how things work and from where they originate, while Hinduism strives to understand the ultimate purposes for the existence of living things. To obtain and broaden the knowledge of the world for spiritual perfection, many refer to the Bhāgavata for guidance because it draws upon a scientific and theological dialogue. Hinduism offers methods to correct and transform itself in course of time. For instance, Hindu views on the development of life include a range of viewpoints in regards to evolution, creationism, and the origin of life within the traditions of Hinduism. For instance, it has been suggested that Wallace-Darwininan evolutionary thought was a part of Hindu thought centuries before modern times. The Shankara and the Sāmkhya did not have a problem with the theory of evolution, but instead, argued about the existence of God and what happened after death. These two distinct groups argued among each other's philosophies because of their texts, not the idea of evolution. With the publication of Darwin's On the Origin of Species, many Hindus were eager to connect their scriptures to Darwinism, finding similarities between Brahma's creation, Vishnu's incarnations, and evolution theories.
Samkhya, the oldest school of Hindu philosophy prescribes a particular method to analyze knowledge. According to Samkhya, all knowledge is possible through three means of valid knowledge –
Pratyakṣa or Dṛṣṭam – direct sense perception,
Anumāna – logical inference and
Śabda or Āptavacana – verbal testimony.
Nyaya, the Hindu school of logic, accepts all these 3 means and in addition accepts one more – Upamāna (comparison).
The accounts of the emergence of life within the universe vary in description, but classically the deity called Brahma, from a Trimurti of three deities also including Vishnu and Shiva, is described as performing the act of 'creation', or more specifically of 'propagating life within the universe' with the other two deities being responsible for 'preservation' and 'destruction' (of the universe) respectively. In this respect some Hindu schools do not treat the scriptural creation myth literally and often the creation stories themselves do not go into specific detail, thus leaving open the possibility of incorporating at least some theories in support of evolution. Some Hindus find support for, or foreshadowing of evolutionary ideas in scriptures, namely the Vedas.
The incarnations of Vishnu (Dashavatara) is almost identical to the scientific explanation of the sequence of biological evolution of man and animals. The sequence of avatars starts from an aquatic organism (Matsya), to an amphibian (Kurma), to a land-animal (Varaha), to a humanoid (Narasimha), to a dwarf human (Vamana), to 5 forms of well developed human beings (Parashurama, Rama, Balarama/Buddha, Krishna, Kalki) who showcase an increasing form of complexity (Axe-man, King, Plougher/Sage, wise Statesman, mighty Warrior). In fact, many Hindu gods are represented with features of animals as well as those of humans, leading many Hindus to easily accept evolutionary links between animals and humans. In India, the home country of Hindus, educated Hindus widely accept the theory of biological evolution. In a survey of 909 people, 77% of respondents in India agreed with Charles Darwin's Theory of Evolution, and 85 per cent of God-believing people said they believe in evolution as well.
As per Vedas, another explanation for the creation is based on the five elements: earth, water, fire, air and aether.
The Hindu religion traces its beginnings to the Vedas. Everything that is established in the Hindu faith such as the gods and goddesses, doctrines, chants, spiritual insights, etc. flow from the poetry of Vedic hymns. The Vedas offer an honor to the sun and moon, water and wind, and to the order in Nature that is universal. This naturalism is the beginning of what further becomes the connection between Hinduism and science.
=== Islam ===
From an Islamic standpoint, science, the study of nature, is considered to be linked to the concept of Tawhid (the Oneness of God), as are all other branches of knowledge. In Islam, nature is not seen as a separate entity, but rather as an integral part of Islam's holistic outlook on God, humanity, and the world. The Islamic view of science and nature is continuous with that of religion and God. This link implies a sacred aspect to the pursuit of scientific knowledge by Muslims, as nature itself is viewed in the Qur'an as a compilation of signs pointing to the Divine. It was with this understanding that science was studied and understood in Islamic civilizations, specifically during the eighth to sixteenth centuries, prior to the colonization of the Muslim world. Robert Briffault, in The Making of Humanity, asserts that the very existence of science, as it is understood in the modern sense, is rooted in the scientific thought and knowledge that emerged in Islamic civilizations during this time. Ibn al-Haytham, an Arab Muslim, was an early proponent of the concept that a hypothesis must be proved by experiments based on confirmable procedures or mathematical evidence—hence understanding the scientific method 200 years before Renaissance scientists. Ibn al-Haytham described his theology:
I constantly sought knowledge and truth, and it became my belief that for gaining access to the effulgence and closeness to God, there is no better way than that of searching for truth and knowledge.
With the decline of Islamic Civilizations in the late Middle Ages and the rise of Europe, the Islamic scientific tradition shifted into a new period. Institutions that had existed for centuries in the Muslim world looked to the new scientific institutions of European powers. This changed the practice of science in the Muslim world, as Islamic scientists had to confront the western approach to scientific learning, which was based on a different philosophy of nature. From the time of this initial upheaval of the Islamic scientific tradition to the present day, Muslim scientists and scholars have developed a spectrum of viewpoints on the place of scientific learning within the context of Islam, none of which are universally accepted or practiced. However, most maintain the view that the acquisition of knowledge and scientific pursuit in general is not in disaccord with Islamic thought and religious belief.
During the thirteenth century, the Caliphate system in the Islamic Empire fell, and scientific discovery thrived. The Islamic Civilization has a long history of scientific advancement; and their theological practices catalyzed a great deal of scientific discovery. In fact, it was due to necessities of Muslim worship and their vast empire that much science and philosophy was created. People needed to know in which direction they needed to pray toward to face Mecca. Many historians through time have asserted that all modern science originates from ancient Greek scholarship; but scholars like Martin Bernal have claimed that most ancient Greek scholarship relied heavily on the work of scholars from ancient Egypt and the Levant. Ancient Egypt was the foundational site of the Hermetic School, which believed that the sun represented an invisible God. Amongst other things, Islamic civilization was key because it documented and recorded Greek scholarship.
==== Ahmadiyya ====
The Ahmadiyya movement emphasize that "there is no contradiction between Islam and science". For example, Ahmadi Muslims universally accept in principle the process of evolution, albeit divinely guided, and actively promote it. Over the course of several decades the movement has issued various publications in support of the scientific concepts behind the process of evolution, and frequently engages in promoting how religious scriptures, such as the Qur'an, supports the concept. For general purposes, the second Khalifa of the community, Mirza Basheer-ud-Din Mahmood Ahmad says:
The Holy Quran directs attention towards science, time and again, rather than evoking prejudice against it. The Quran has never advised against studying science, lest the reader should become a non-believer; because it has no such fear or concern. The Holy Quran is not worried that if people will learn the laws of nature its spell will break. The Quran has not prevented people from science, rather it states, "Say, 'Reflect on what is happening in the heavens and the earth.'" (Al Younus)
=== Jainism ===
==== Biology ====
Jainism classifies life into two main divisions those who are static by nature (sthavar) and those who are mobile (trasa).
Jain texts describes life in plant long before Jagdish Chandra Bose proved that plants have life. In the Jain philosophy the plant lives are termed as 'Vanaspatikaya'.
==== Jainism and non-creationism ====
Jain theory of causality holds that a cause and its effect are always identical in nature and an immaterial entity like a creator God cannot be the cause of a material entity like the universe. According to Jain belief, it is not possible to create matter out of nothing.[a] The universe and its constituents– soul, matter, space, time, and natural laws have always existed (a static universe, similar to that proposed by the steady state cosmological model).
== Surveys on scientists and the general public ==
=== Scientists ===
Between 1901 and 2000, 654 Nobel prize laureates belonged to 28 different religions. Most (65%) have identified Christianity in its various forms as their religious preference. Specifically on the science-related prizes, Christians have won a total of 73% of all the Chemistry, 65% in Physics, 62% in Medicine, and 54% in all Economics awards. Jews have won 17% of the prizes in Chemistry, 26% in Medicine, and 23% in Physics. Atheists, Agnostics, and Freethinkers have won 7% of the prizes in Chemistry, 9% in Medicine, and 5% in Physics. Muslims have won 13 prizes (three were in scientific categories).
According to scholar Benjamin Beit-Hallahmi, between 1901–2001, about 57% of laureates in scientific fields were Christians, and 26% were of Jewish descent (including Jewish atheists).
==== Global ====
According to a global study on scientists, a significant portion of scientists around the world have religious identities, beliefs, and practices overall. Furthermore, the majority of scientists do not believe there is inherent conflict in being religious and a scientist and stated that "the conflict perspective on science and religion is an invention of the West" since such a view is not prevalent among most of scientists around the world. Instead of seeing religion and science as 'always in conflict' they rather view it through the lenses of various cultural dimensions to the relations between religion and science.
==== Europe ====
According to a study from 2023 "30–39% of Western-European researchers identify with “some religious affiliation”. "30–37% of scientists identify as non-believers or atheists, and an additional 10–28% as agnostic (with wide geographical differences)".
==== United States ====
In 1916, 1,000 leading American scientists were randomly chosen from American Men of Science and 42% believed God existed, 42% disbelieved, and 17% had doubts/did not know; however, when the study was replicated 80 years later using American Men and Women of Science in 1996, the results were very much the same with 39% believing God exists, 45% disbelieved, and 15% had doubts/did not know. In the same 1996 survey, for scientists in the fields of biology, mathematics, and physics/astronomy, belief in a god that is "in intellectual and affective communication with humankind" was most popular among mathematicians (about 45%) and least popular among physicists (about 22%).
In terms of belief in God among elite scientists, such as "great scientists" in the "American Men of Science" or members of the National Academies of Science; 53% disbelieved, 21% were agnostic, and 28% believed in 1914; 68% disbelieved, 17% were agnostic, and 15% believed in 1933; and 72% disbelieved, 21% were agnostic, and 7% believed in 1998. However Eugenie Scott argued that there are methodological issues in the study, including ambiguity in the questions such using a personal definition of God instead of broader definitions of God. A study with simplified wording to include impersonal or non-interventionist ideas of God concluded that 40% of "prominent scientists" in the US believe in a god.
Others have also observed some methodological issues which impacted the results.
A survey conducted between 2005 and 2007 by Elaine Howard Ecklund of University at Buffalo, The State University of New York of 1,646 natural and social science professors at 21 US research universities found that, in terms of belief in God or a higher power, more than 60% expressed either disbelief or agnosticism and more than 30% expressed belief. More specifically, nearly 34% answered "I do not believe in God" and about 30% answered "I do not know if there is a God and there is no way to find out." In the same study, 28% said they believed in God and 8% believed in a higher power that was not God. Ecklund stated that scientists were often able to consider themselves spiritual without religion or belief in god. Ecklund and Scheitle concluded, from their study, that the individuals from non-religious backgrounds disproportionately had self-selected into scientific professions and that the assumption that becoming a scientist necessarily leads to loss of religion is untenable since the study did not strongly support the idea that scientists had dropped religious identities due to their scientific training. Instead, factors such as upbringing, age, and family size were significant influences on religious identification since those who had religious upbringing were more likely to be religious and those who had a non-religious upbringing were more likely to not be religious. The authors also found little difference in religiosity between social and natural scientists.
In terms of perceptions, most social and natural scientists from 21 American universities did not perceive conflict between science and religion, while 37% did. However, in the study, scientists who had experienced limited exposure to religion tended to perceive conflict. In the same study they found that nearly one in five atheist scientists who are parents (17%) are part of religious congregations and have attended a religious service more than once in the past year. Some of the reasons for doing so are their scientific identity (wishing to expose their children to all sources of knowledge so they can make up their own minds), spousal influence, and desire for community.
A 2009 report by the Pew Research Center found that members of the American Association for the Advancement of Science (AAAS) were "much less religious than the general public," with 51% believing in some form of deity or higher power. Specifically, 33% of those polled believe in God, 18% believe in a universal spirit or higher power, and 41% did not believe in either God or a higher power. 48% say they have a religious affiliation, equal to the number who say they are not affiliated with any religious tradition. 17% were atheists, 11% were agnostics, 20% were nothing in particular, 8% were Jewish, 10% were Catholic, 16% were Protestant, 4% were Evangelical, 10% were other religion. The survey also found younger scientists to be "substantially more likely than their older counterparts to say they believe in God". Among the surveyed fields, chemists were the most likely to say they believe in God.
Elaine Ecklund conducted a study from 2011 to 2014 involving the general US population, including rank and file scientists, in collaboration with the AAAS. The study noted that 76% of the scientists identified with a religious tradition. 85% of evangelical scientists had no doubts about the existence of God, compared to 35% of the whole scientific population. In terms of religion and science, 85% of evangelical scientists saw no conflict (73% collaboration, 12% independence), while 75% of the whole scientific population saw no conflict (40% collaboration, 35% independence).
Religious beliefs of US professors were examined using a nationally representative sample of more than 1,400 professors. They found that in the social sciences: 23% did not believe in God, 16% did not know if God existed, 43% believed God existed, and 16% believed in a higher power. Out of the natural sciences: 20% did not believe in God, 33% did not know if God existed, 44% believed God existed, and 4% believed in a higher power. Overall, out of the whole study: 10% were atheists, 13% were agnostic, 19% believe in a higher power, 4% believe in God some of the time, 17% had doubts but believed in God, 35% believed in God and had no doubts.
In 2005, Farr Curlin, a University of Chicago Instructor in Medicine and a member of the MacLean Center for Clinical Medical Ethics, noted in a study that doctors tend to be science-minded religious people. He helped author a study that "found that 76 percent of doctors believe in God and 59 percent believe in some sort of afterlife." Furthermore, "90 percent of doctors in the United States attend religious services at least occasionally, compared to 81 percent of all adults." He reasoned, "The responsibility to care for those who are suffering and the rewards of helping those in need resonate throughout most religious traditions.". A study from 2017 showed 65% of physicians believe in God.
==== Other or multiple countries ====
According to the Study of Secularism in Society and Culture's report on 1,100 scientists in India: 66% are Hindu, 14% did not report a religion, 10% are atheist/no religion, 3% are Muslim, 3% are Christian, 4% are Buddhist, Sikh or other. 39% have a belief in a god, 6% have belief in a god sometimes, 30% do not believe in a god but believe in a higher power, 13% do not know if there is a god, and 12% do not believe in a god. 49% believe in the efficacy of prayer, 90% strongly agree or somewhat agree with approving degrees in Ayurvedic medicine. Furthermore, the term "secularism" is understood to have diverse and simultaneous meanings among Indian scientists: 93% believe it to be tolerance of religions and philosophies, 83% see it as involving separation of church and state, 53% see it as not identifying with religious traditions, 40% see it as absence of religious beliefs, and 20% see it as atheism. Accordingly, 75% of Indian scientists had a "secular" outlook in terms of being tolerant of other religions.
According to the Religion Among Scientists in International Context (RASIC) study on 1,581 scientists from the United Kingdom and 1,763 scientists from India, along with 200 interviews: 65% of U.K. scientists identified as nonreligious and only 6% of Indian scientists identify as nonreligious, 12% of scientists in the U.K. attend religious services on a regular basis and 32% of scientists in India do. In terms of the Indian scientists, 73% of scientists responded that there are basic truths in many religions, 27% said they believe in God and 38% expressed belief in a higher power of some kind. In terms of perceptions of conflict between science and religion, less than half of both U.K. scientists (38%) and Indian scientists (18%) perceived conflict between religion and science.
According to Elaine Ecklund's research on 1,293 atheist scientists from the US and UK, a majority of atheist scientists came from a nonreligious upbringing and never had a religious affiliation. Also, fewer than half of the atheist scientists who were exposed to religion in their youth said science played a role in them becoming an atheist.
=== General public ===
Global studies which have pooled data on religion and science from 1981 to 2001, have noted that countries with greater faith in science also often have stronger religious beliefs, while less religious countries have more skepticism of the impact of science and technology.
Other research cites the National Science Foundation's finding that America has more favorable public attitudes towards science than Europe, Russia, and Japan despite differences in levels of religiosity in these cultures.
Other cross-national studies have found no correlations supporting the contention that religiosity undermines interest in science topics or activities among the general populations globally.
Cross-cultural studies indicate that people tend to use both natural and supernatural explanations for explaining numerous things about the world such as illness, death, and origins. In other words, they do not think of natural and supernatural explanations as antagonistic or dichotomous, but instead see them as coexisting and complementary. The reconciliation of natural and supernatural explanations is normal and pervasive from a psychological standpoint across cultures.
==== Europe ====
A study conducted on adolescents from Christian schools in Northern Ireland, noted a positive relationship between attitudes towards Christianity and science once attitudes towards scientism and creationism were accounted for.
A study on people from Sweden concludes that though the Swedes are among the most non-religious, paranormal beliefs are prevalent among both the young and adult populations. This is likely due to a loss of confidence in institutions such as the Church and Science.
Concerning specific topics like creationism, it is not an exclusively American phenomenon. A poll on adult Europeans revealed that 40% believed in naturalistic evolution, 21% in theistic evolution, 20% in special creation, and 19% are undecided; with the highest concentrations of young earth creationists in Switzerland (21%), Austria (20%), Germany (18%). Other countries such as Netherlands, Britain, and Australia have experienced growth in such views as well.
==== United States ====
According to a 2015 Pew Research Center Study on the public perceptions on science, people's perceptions on conflict with science have more to do with their perceptions of other people's beliefs than their own personal beliefs. For instance, the majority of people with a religious affiliation (68%) saw no conflict between their own personal religious beliefs and science while the majority of those without a religious affiliation (76%) perceived science and religion to be in conflict. The study noted that people who are not affiliated with any religion, also known as "religiously unaffiliated", often have supernatural beliefs and spiritual practices despite them not being affiliated with any religion and also that "just one-in-six religiously unaffiliated adults (16%) say their own religious beliefs conflict with science." Furthermore, the study observed, "The share of all adults who perceive a conflict between science and their own religious beliefs has declined somewhat in recent years, from 36% in 2009 to 30% in 2014. Among those who are affiliated with a religion, the share of people who say there is a conflict between science and their personal religious beliefs dropped from 41% to 34% during this period."
In a 2024 Pew research center report, only 35% of "nones" (atheist, agnostics, and nothing in particular on religious affiliation); believe that the natural world is all there is, while the majority of nones (63%) believe there are spiritual things beyond the world; and the majority of nones (56%) also believe there are some things that science cannot explain.
The 2013 MIT Survey on Science, Religion and Origins examined the views of religious people in America on origins science topics like evolution, the Big Bang, and perceptions of conflicts between science and religion. It found that a large majority of religious people see no conflict between science and religion and only 11% of religious people belong to religions openly rejecting evolution. The fact that the gap between personal and official beliefs of their religions is so large suggests that part of the problem, might be defused by people learning more about their own religious doctrine and the science it endorses, thereby bridging this belief gap. The study concluded that "mainstream religion and mainstream science are neither attacking one another nor perceiving a conflict." Furthermore, they note that this conciliatory view is shared by most leading science organizations such as the American Association for the Advancement of Science (AAAS).
A study was made in collaboration with the AAAS collecting data on the general public from 2011 to 2014, with the focus on evangelicals and evangelical scientists. Even though evangelicals make up only 26% of the US population, the study found that nearly 70 percent of all evangelical Christians do not view science and religion as being in conflict with each other (48% saw them as complementary and 21% saw them as independent) while 73% of the general US population saw no conflict either.
According to Elaine Ecklund's 2018 study, the majority of religious groups see religion and science in collaboration or independent of each other, while the majority of groups without religion see science and religion in conflict.
Other lines of research on perceptions of science among the American public conclude that most religious groups see no general epistemological conflict with science and they have no differences with nonreligious groups in the propensity of seeking out scientific knowledge, although there may be subtle epistemic or moral conflicts when scientists make counterclaims to religious tenets. Findings from the Pew Center note similar findings and also note that the majority of Americans (80–90%) show strong support for scientific research, agree that science makes society and individual's lives better, and 8 in 10 Americans would be happy if their children were to become scientists. Even strict creationists tend to have very favorable views on science.
According to a 2007 poll by the Pew Forum, "while large majorities of Americans respect science and scientists, they are not always willing to accept scientific findings that squarely contradict their religious beliefs." The Pew Forum states that specific factual disagreements are "not common today", though 40% to 50% of Americans do not accept the evolution of humans and other living things, with the "strongest opposition" coming from evangelical Christians at 65% saying life did not evolve. 51% of the population believes humans and other living things evolved: 26% through natural selection only, 21% somehow guided, 4% do not know. In the U.S., biological evolution is the only concrete example of conflict where a significant portion of the American public denies scientific consensus for religious reasons. In terms of advanced industrialized nations, the United States is the most religious.
A 2009 study from the Pew Research Center on Americans perceptions of science, showed a broad consensus that most Americans, including most religious Americans, hold scientific research and scientists themselves in high regard. The study showed that 84% of Americans say they view science as having a mostly positive impact on society. Among those who attend religious services at least once a week, the number is roughly the same at 80%. Furthermore, 70% of U.S. adults think scientists contribute "a lot" to society.
A 2011 study on a national sample of US college students examined whether these students viewed the science / religion relationship as reflecting primarily conflict, collaboration, or independence. The study concluded that the majority of undergraduates in both the natural and social sciences do not see conflict between science and religion. Another finding in the study was that it is more likely for students to move away from a conflict perspective to an independence or collaboration perspective than towards a conflict view.
In the US, people who had no religious affiliation were no more likely than the religious population to have New Age beliefs and practices.
== See also ==
== References ==
== Sources ==
== Further reading ==
== External links == | Wikipedia/Scientific_method_and_religion |
The MacLean Center for Clinical Medical Ethics, founded in 1981, is a non-profit clinical medical ethics research institute based in the United States. Founded by its director, Mark Siegler, the MacLean Center for Clinical Medical Ethics aims to improve patient care and outcomes by promoting research in clinical medical ethics by educating physicians, nurses, and other health care professionals and by helping University of Chicago Medicine patients, families, and health care providers identify and resolve ethical dilemmas. The center has trained over 410 fellows, including many physicians, attorneys, PhDs and bioethicists.
== History ==
In 1983, with support from Dorothy J. MacLean and the MacLean family, the University of Chicago established the nation's first program devoted to clinical medical ethics. Dr. Mark Siegler was appointed its founding director. The MacLean Center for Clinical Medical Ethics was pivotal in establishing and expanding the field of clinical medical ethics. It did this through its pioneering program in ethics fellowship training; its foundational role in ethics consultation; its close involvement in research and the protection of human subjects through an innovative concept of "research ethics consultation;" and by encouraging scholarly research and publication in clinical medical ethics. The center also encouraged the "empirical turn" in bioethics scholarship, an approach that uses clinical epidemiology, health services research, and decision science techniques to study ethical matters in clinical practice. The center's current and former faculty and fellows have published more than 210 books on topics related to medicine and medical ethics.
== Fellowship ==
The MacLean for Clinical Medical Ethics at the University of Chicago offers the oldest, largest, and most successful clinical ethics fellowship in the world. Dr. Mark Siegler, the Founding Director of the MacLean Center, created the first clinical ethics fellowship in the nation in 1981. Since then, the MacLean Center faculty members have trained more than 320 fellows, many of whom have gone on to direct their own ethics programs. While most fellows are physicians, the center welcomes those interested in medical ethics from any perspective, including philosophy, theology, nursing, law, and the social sciences. The MacLean Center, with more than 45 faculty members from many disciplines, provides training in clinical medical ethics and specialized fellowships in surgical ethics and pediatric ethics. Prior to 2014, through a partnership with the United States Veterans Administration (VA) hospital system, two or three VA medical professionals per year are selected by the VA through a national search to participate in the MacLean Center ethics fellowship training program.
== Consultation ==
Since 1981, The MacLean Center has offered clinical ethics consultations to assist patients, families, physicians, nurses, and students. MacLean Center fellows and faculty wrote many of the early papers guiding the field of clinical ethics consultation. The Center developed the concept of "research ethics consultation" in 1987 and has continued to offer this service to translational researchers and to the IRB.
== Research ==
MacLean Center research has been on the cutting edge of both medicine and ethics, with clinical research proceeding in tandem with medical advances. The MacLean Center was involved in the introduction of pediatric live-donor liver transplantation in 1989. This new procedure raised complex ethical questions about medical innovation, risk/benefit balancing, informed consent, and the protection of "living organ donors". The MacLean Center worked for two years with transplant experts at the University of Chicago to review the ethical issues, publish protocols, and encourage professional discussion of the procedure before it was first performed on a patient. The MacLean Center's transplant work is one example of the wide range of ethics-related research projects undertaken by its faculty. The MacLean Center faculty publishes on subjects such as research ethics, health policy, health disparities, end of life care, surgical ethics, pediatric outcomes, genetics, and transplantation ethics. Current and former MacLean Center faculty and fellows have published more than 150 books in the field of medical ethics.
== Events ==
For over 30 years, the MacLean Center has directed and sponsored programs form faculty and students at the University of Chicago. Since 1984, The Interdisciplinary Faculty Seminar Series has organized weekly meetings throughout the academic year to provide a sustainable interdisciplinary forum on issues in medicine and medical ethics. Additionally, every November, the MacLean Center hosts the Dorothy J. MacLean Fellows Conference, which draws speakers and audiences from a wide range of disciplines.
=== Interdisciplinary Faculty Seminar Series ===
In 1981, under the auspices of the MacLean Center, Mark Siegler and Richard Epstein organized a yearlong interdisciplinary seminar series on Bad Outcomes after Medical Intervention. The success of that initial seminar program demonstrated that there was great interest at the University of Chicago in creating a sustainable interdisciplinary forum to discuss health-related subjects with colleagues from across campus. Since 1981, the MacLean Center has sponsored an annual seminar series that has examined the ethical aspects of one key health related issue each year. Previous topics have included: Organ Transplantation, Pediatric Ethics, End-of-Life Care, Global Health, Health Care Disparities, Medical Professionalism, Confidentiality, and Pharmaceutical Innovation and Regulation.
=== Annual Dorothy J. MacLean Fellows Conference ===
Each year for the past 28 years, the MacLean Center has hosted a conference that draws speakers, primarily former fellows of the MacLean Center, who discuss today's issues in clinical medical ethics. The conference audience usually numbers 250 to 300 and includes more than 100 former faculty and fellows. The conference remembers Dorothy Jean MacLean, who helped create the MacLean Center and was deeply committed to its work. D.J. MacLean believed that education was the best way to improve the world and throughout her life supported many leading educational institutions.
The 28th consecutive MacLean Fellows Conference will be held on November 11–12, 2016. More than 35 former fellows will be giving presentations.
== Resources ==
=== Library ===
The MacLean Center Library, started by generous donations from Drs. Edmund Pellegrino, Leon Kass, and James J. Smith, as well as by Dr. Sulmasy and Dr. Siegler, exists as a non-lending resource for faculty, fellows, and students working in the field of clinical medical ethics. The library currently houses an interdisciplinary collection of over five-thousand books and visual media. The library subscribes to twenty-five journals related to medicine and ethics, and presently maintains complete collections from Volume 1 of many of the core journals in medical ethics including the "Hastings Center Report", Journal of Clinical Ethics, "Cambridge Quarterly of Healthcare Ethics", "Kennedy Institute of Ethics Journal", "Journal of Medicine and Philosophy", ""National Catholic Bioethics Quarterly"", and "Theoretical Medicine and Bioethics". The library recently received an additional donation of over 1,300 books from the personal libraries of Drs. Edmund Pellegrino and Professor Alan J. Wiesbard. The library is currently working to digitize and catalog its collection of over 400 videos related to medical ethics that date back to the 1980. Library staff anticipates making this collection available to faculty and students online by the end of the 2014 academic year integrating its catalogue with the University of Chicago central catalogue.
== Awards and honors ==
=== Cornerstone Award ===
The MacLean Center received the Cornerstone Award on October 25, 2013 from the American Society for Bioethics and Humanities for "outstanding contributions from an institution that has helped shape the direction of the fields of bioethics and/or medical humanities." The MacLean Center joined the three other institutions that have received this award in the past: the Hastings Center, the Kennedy Institute of Ethics, and the Institute for Medical Humanities at Galveston, Texas.
=== The MacLean Center Prize ===
The MacLean Center Prize in Clinical Ethics and Health Outcomes celebrates individuals who have made transformative contributions to the field of clinical ethics through scholarship, practice, leadership, and policy development. The MacLean Center Prize of $50,000 is the largest prize in Clinical Ethics.
The first recipient of the MacLean Center Prize was Dr. John Wennberg, the Peggy Y. Thomson Professor Emeritus for the Evaluative Clinical Sciences at Dartmouth Medical School.
The most recent recipient of the MacLean Center Prize, recognized in November 2012, is " Dr. Peter Singer ". A former MacLean Center Fellow, Dr. Singer has dedicated much of his career to the ethics of global health.
== References ==
== External links ==
Official website
Guide to the University of Chicago MacLean Center for Clinical Medical Ethics Records 1961-2009 at the University of Chicago Special Collections Research Center | Wikipedia/MacLean_Center_for_Clinical_Medical_Ethics |
Science, Evolution, and Creationism is a publication by the United States National Academy of Sciences. The book's authors intended to provide a current and comprehensive explanation of evolution and "its importance in the science classroom". It was "intended for use by scientists, teachers, parents, and school board members who wanted to engage in more constructive conversations with others who remain uncertain about evolution and its place in the public school curriculum." The book, published on January 3, 2008, is available as a free PDF file on the National Academies Press website.
Science, Evolution, and Creationism differs from prior National Academy of Sciences publications regarding creation and evolution in public education and the creation–evolution controversy; it is intended "specifically for the lay public", devoting much of its space to "explaining the differences between science and religion, and asserting that acceptance of evolution does not require abandoning belief in God." The book provides statements from notable biologists and clergy members to support the claim that "attempts to pit science and religion against each other create controversy where none needs to exist."
The authors of Science, Evolution, and Creationism, who include Francisco J. Ayala and Bruce Alberts, highlight developments in evolutionary biology and its relevance to the study of emerging infectious diseases, the 2006 discovery of the transitional fossil Tiktaalik, and the application of evolutionary theory in many areas of science and engineering beyond biology.
The book was released as several states, particularly Texas and Florida, considered revisions in state science standards.
A study at Arizona State University used the book as part of a two-week module, within an introductory biology course, focusing on science, evolution, and religion. The percentage of students who held the view that there was a conflict between religion and evolution was reduced by about half.
== Critical response ==
In an interview on NBC, Glenn Branch, deputy director of the National Center for Science Education, called the publication "a definitive statement from a leading scientific authority about the scientific bankruptcy of intelligent design creationism."
Praise for the publication was received from Lawrence Krauss and editorials in Nature, New Scientist, and several newspapers.
== References ==
== External links ==
Science, Evolution, and Creationism full text online from the National Academies Press | Wikipedia/Science,_Evolution,_and_Creationism |
The Graduate Theological Union (GTU) is a consortium of eight private independent American theological schools and eleven centers and affiliates. Seven of the theological schools are located in Berkeley, California. The GTU was founded in 1962 and their students can take courses at the University of California, Berkeley. Additionally, some of the GTU consortial schools are part of other California universities such as Santa Clara University (Jesuit School of Theology) and California Lutheran University (Pacific Lutheran Theological Seminary). Most of the GTU consortial schools are located in the Berkeley area with the majority north of the campus in a neighborhood known as "Holy Hill" due to the cluster of GTU seminaries and centers located there.
== History and administration ==
Many of the GTU's constituent seminaries were established at various locations throughout the Bay Area in the early 20th or even the late 19th centuries. Because of the foundation of the University of California, several of them relocated to Berkeley and established cooperative relationships with the university. In the wake of the formation of the World Council of Churches and the Second Vatican Council, Bay Area seminaries began negotiations to form a cooperative degree program. In 1962, agreement between the Berkeley Baptist Divinity School (now Berkeley School of Theology), Episcopalian Church Divinity School of the Pacific, Pacific Lutheran Theological Seminary and San Francisco Theological Seminary enabled for the incorporation of the Graduate Theological Union in 1962. In 1964, the Pacific School of Religion, St. Albert's College (now the Dominican School of Philosophy and Theology) and Starr King School for the Ministry joined the GTU consortium. In 1966, Alma College relocated to Berkeley and was renamed the Jesuit School of Theology at Berkeley. In 1968, the Franciscan School of Theology moved to Berkeley from Santa Barbara and joined the GTU consortium, although in 2013 it merged with the University of San Diego, leaving the consortium and relocating to Oceanside, California. By 1971, the GTU was fully accredited by the Association of Theological Schools.
In 1969, the GTU common library was established and the individual libraries of the seminaries were merged into one collection. In the 1970s, construction began on a Louis I. Kahn-designed building to house the GTU library. The main library building was completed in 1987 and was named the Flora Lamson Hewlett Library in honor of the Hewlett Foundation.
=== Presidents and academic deans ===
The dean of the GTU is the chief academic officer. The dean also chairs the GTU's council of deans, which is composed of the academic deans of the member schools. Traditionally, deans have held the John Dillenberger Professorship in their general field of specialization. The fifth dean, Margaret Miles, was the John Dillenberger Professor of Historical Theology while the sixth dean, Arthur Holder, was the John Dillenberger Professor of Christian Spirituality. The current dean, Uriah Y. Kim, is the John Dillenberger Professor of Biblical Studies.
== Member seminaries, academic centers, and affiliates ==
=== Consortial seminaries ===
Berkeley School of Theology (American Baptist Churches USA)
Church Divinity School of the Pacific (Episcopal)
Dominican School of Philosophy and Theology
Institute of Buddhist Studies
Jesuit School of Theology of Santa Clara University
Pacific Lutheran Theological Seminary (ELCA)
Pacific School of Religion (United Church of Christ, Disciples of Christ, and United Methodist Church)
San Francisco Theological Seminary (Presbyterian Church (USA))
=== Academic centers and affiliates ===
Center for the Arts and Religion
Center for Islamic Studies
Center for Swedenborgian Studies
Center for Theology and the Natural Sciences
Mira & Ajay Shingal Center for Dharma Studies
New College Berkeley
Patriarch Athenagoras Orthodox Institute
Richard S. Dinner Center for Jewish Studies
Newbigin House of Studies
Wilmette Institute
== Academics ==
The GTU offers the Doctor of Philosophy (Ph.D.) degree and the Master of Arts (MA) degree in cooperation with its member seminaries. GTU consortial seminaries variously offer Th.M., M.Div., Doctor of Ministry (D.Min.), S.T.B., S.T.L., and S.T.D. degrees. The GTU also offers non-degree certificates in Interreligious Chaplaincy and Interreligious Studies. Ph.D. students are encouraged not only to take advantage of the academic resources available to them at the University of California at Berkeley, but are also required to include a non-GTU scholar in their exams or dissertation committees. As such, students have collaborated with UCB faculty members in the anthropology, critical theory, ethnic studies, history, philosophy, sociology, etc. departments.
=== Departments and certificate programs ===
There are four doctoral departments, with more than 30 concentrations, encompassing the breadth of religious and theological scholarship at the GTU. The Sacred Texts and Interpretation department focuses on Hebrew Bible, New Testament, Rabbinic Literature, and studies in the sacred texts of Islamic and Hindu traditions. Historical and Cultural Studies of Religions encompasses studies in history of religions, art and religion, interreligious studies, and sociology of religion. Theology and Ethics focuses on theological and ethical reflections in the Christian, Jewish, Islamic, and Hindu traditions. Other concentrations include comparative theology/ethics, philosophical theology, theology and science, and aesthetics. Religion and Practice focuses on homiletics, liturgical studies, missiology, practical theology, and religious education. The GTU also offers certificates in specialized studies.
All degree seeking students at GTU may take any classes offered at the University of California, Berkeley, and have access and borrowing privileges at the University of California, Berkeley and Stanford University libraries. Only Ph.D. students have unrestricted access to registering for UCB classes (subject to approval of course instructors). Cross-registration opportunities are also available at Dominican University of California, Holy Names University, and Mills College. Additionally, students can participate in international exchange programs.
=== Berkeley Journal of Religion and Theology ===
The GTU's in-house academic journal is the Berkeley Journal of Religion and Theology. The journal is managed by current doctoral students, although peer-reviewers include members of the consortial doctoral faculty. All issues are available free online.
== Campus ==
Although the GTU consortium occupies many buildings throughout the Bay Area, only three buildings are owned by the GTU. The largest of the buildings is the Flora Lamson Hewlett Library, one of the largest theological libraries in the world, with around 529,000 volumes.
== Notable alumni ==
David Batstone, Professor of business ethics at the University of San Francisco
Virginia Burrus, Bishop W. Earl Ledden Professor of Religion at Syracuse University
James Donahue, President of Saint Mary's College of California and 6th president of the GTU.
Eileen Chamberlain Donahoe, U.S. Ambassador to the United Nations Human Rights Council
Heup Young Kim, President of the Korea Forum for Science and Life, Korean Society of Systematic Theology, and Honorary Professor of Theology at Kangnam University.
Kristin Johnston Largen, President of Wartburg Theological Seminary
Nancey Murphy, Professor of Christian philosophy at Fuller Theological Seminary
Mark L. Poorman, President of the University of Portland.
Robert John Russell, Ian Barbour Professor of Theology at the Graduate Theological Union and Director of the Center for Theology and the Natural Sciences.
Gregory Sterling, Dean of Yale Divinity School and The Reverend Henry L. Slack Dean and Lillian Claus Professor of New Testament at Yale University
George Tinker, Clifford Baldridge Professor of American Indian Cultures and Religious Traditions at Iliff School of Theology
Shibley Telhami, Anwar Sadat Professor for Peace and Development at the University of Maryland
Wesley Wildman, Professor of Philosophy, Theology, and Ethics and Founding Member of Faculty of Computing and Data Sciences at Boston University
Laurie Zoloth, Margaret E. Burton Professor at the University of Chicago Divinity School and former president of the American Academy of Religion.
Hamza Yusuf, Co-founder of Zaytuna College.
Douglas E. Oakman, Professor of New Testament at Pacific Lutheran University.
== Faculty ==
The GTU draws its consortial faculty from its constituent seminaries and centers. Although faculty members are employed at their respective seminaries and centers, they commit to supervising doctoral and masters students, as well as occasionally teaching advanced GTU-wide courses.
=== Notable current faculty ===
Christopher Ocker, Professor of Church History at San Francisco Theological Seminary and affiliate Professor of History at University of California, Berkeley.
Ted Peters, Distinguished Research Professor of Systematic Theology at Pacific Lutheran Theological Seminary and Affiliate Professor at the Ayala Center for Theology and Natural Sciences.
Robert John Russell, Ian Barbour Professor of Theology and Science and Director of the Ayala Center for Theology and Science.
=== Notable former faculty ===
Former faculty members include Naomi Seidman, Daniel C. Matt, David Alexander, John Dillenberger, and Roy I. Sano.
== References ==
== External links ==
Official website | Wikipedia/Center_for_Theology_and_the_Natural_Sciences |
The relationship between religion and science involves discussions that interconnect the study of the natural world, history, philosophy, and theology. Even though the ancient and medieval worlds did not have conceptions resembling the modern understandings of "science" or of "religion", certain elements of modern ideas on the subject recur throughout history. The pair-structured phrases "religion and science" and "science and religion" first emerged in the literature during the 19th century. This coincided with the refining of "science" (from the studies of "natural philosophy") and of "religion" as distinct concepts in the preceding few centuries—partly due to professionalization of the sciences, the Protestant Reformation, colonization, and globalization. Since then the relationship between science and religion has been characterized in terms of "conflict", "harmony", "complexity", and "mutual independence", among others.
Both science and religion are complex social and cultural endeavors that may vary across cultures and change over time. Most scientific and technical innovations until the scientific revolution were achieved by societies organized by religious traditions. Ancient pagan, Islamic, and Christian scholars pioneered individual elements of the scientific method. Roger Bacon, often credited with formalizing the scientific method, was a Franciscan friar and medieval Christians who studied nature emphasized natural explanations. Confucian thought, whether religious or non-religious in nature, has held different views of science over time. Many 21st-century Buddhists view science as complementary to their beliefs, although the philosophical integrity of such Buddhist modernism has been challenged. While the classification of the material world by the ancient Indians and Greeks into air, earth, fire, and water was more metaphysical, and figures like Anaxagoras questioned certain popular views of Greek divinities, medieval Middle Eastern scholars empirically classified materials.
Events in Europe such as the Galileo affair of the early 17th century, associated with the scientific revolution and the Age of Enlightenment, led scholars such as John William Draper to postulate (c. 1874) a conflict thesis, suggesting that religion and science have been in conflict methodologically, factually and politically throughout history. Some contemporary philosophers and scientists, such as Richard Dawkins, Lawrence Krauss, Peter Atkins, and Donald Prothero subscribe to this thesis; however, historians such as Stephen Shapin state "it is a very long time since these attitudes have been held by historians of science."
Many scientists, philosophers, and theologians throughout history, from Augustine of Hippo to Thomas Aquinas to Francisco Ayala, Kenneth R. Miller, and Francis Collins, have seen compatibility or interdependence between religion and science. Biologist Stephen Jay Gould regarded religion and science as "non-overlapping magisteria", addressing fundamentally separate forms of knowledge and aspects of life. Some historians of science and mathematicians, including John Lennox, Thomas Berry, and Brian Swimme, propose an interconnection between science and religion, while others such as Ian Barbour believe there are even parallels. Public acceptance of scientific facts may sometimes be influenced by religious beliefs such as in the United States, where some reject the concept of evolution by natural selection, especially regarding Human beings. Nevertheless, the American National Academy of Sciences has written that "the evidence for evolution can be fully compatible with religious faith",
a view endorsed by many religious denominations.
== History ==
=== Concepts of science and religion ===
The concepts of "science" and "religion" are a recent invention: "religion" emerged in the 17th century in the midst of colonization, globalization and as a consequence of the Protestant reformation. "Science" emerged in the 19th century in the midst of attempts to narrowly define those who studied nature. Originally what is now known as "science" was pioneered as "natural philosophy".
It was in the 19th century that the terms "Buddhism", "Hinduism", "Taoism", "Confucianism" and "World Religions" first emerged. In the ancient and medieval world, the etymological Latin roots of both science (scientia) and religion (religio) were understood as inner qualities of the individual or virtues, never as doctrines, practices, or actual sources of knowledge.
The 19th century also experienced the concept of "science" receiving its modern shape with new titles emerging such as "biology" and "biologist", "physics", and "physicist", among other technical fields and titles; institutions and communities were founded, and unprecedented applications to and interactions with other aspects of society and culture occurred. The term scientist was coined by the naturalist-theologian William Whewell in 1834 and it was applied to those who sought knowledge and understanding of nature. From the ancient world, starting with Aristotle, to the 19th century, the practice of studying nature was commonly referred to as "natural philosophy". Isaac Newton's book Philosophiae Naturalis Principia Mathematica (1687), whose title translates to "Mathematical Principles of Natural Philosophy", reflects the then-current use of the words "natural philosophy", akin to "systematic study of nature". Even in the 19th century, a treatise by Lord Kelvin and Peter Guthrie Tait's, which helped define much of modern physics, was titled Treatise on Natural Philosophy (1867).
It was in the 17th century that the concept of "religion" received its modern shape despite the fact that ancient texts like the Bible, the Quran, and other texts did not have a concept of religion in the original languages and neither did the people or the cultures in which these texts were written. In the 19th century, Max Müller noted that what is called ancient religion today, would have been called "law" in antiquity. For example, there is no precise equivalent of "religion" in Hebrew, and Judaism does not distinguish clearly between religious, national, racial, or ethnic identities. The Sanskrit word "dharma", sometimes translated as "religion", also means law or duty. Throughout classical India, the study of law consisted of concepts such as penance through piety and ceremonial as well as practical traditions. Medieval Japan at first had a similar union between "imperial law" and universal or "Buddha law", but these later became independent sources of power. Throughout its long history, Japan had no concept of "religion" since there was no corresponding Japanese word, nor anything close to its meaning, but when American warships appeared off the coast of Japan in 1853 and forced the Japanese government to sign treaties demanding, among other things, freedom of religion, the country had to contend with this Western idea.
=== Middle Ages and Renaissance ===
The development of sciences (especially natural philosophy) in Western Europe during the Middle Ages, has a considerable foundation in the works of the Arabs who translated Greek and Latin compositions. The works of Aristotle played a major role in the institutionalization, systematization, and expansion of reason. Christianity accepted reason within the ambit of faith. In Christendom, ideas articulated via divine revelation were assumed to be true, and thus via the law of non-contradiction, it was maintained that the natural world must accord with this revealed truth. Any apparent contradiction would indicate either a misunderstanding of the natural world or a misunderstanding of revelation. The prominent scholastic Thomas Aquinas writes in the Summa Theologica concerning apparent contradictions:
"In discussing questions of this kind two rules are to observed, as Augustine teaches (Gen. ad lit. i, 18). The first is, to hold the truth of Scripture without wavering. The second is that since Holy Scripture can be explained in a multiplicity of senses, one should adhere to a particular explanation, only in such measure as to be ready to abandon it, if it be proved with certainty to be false; lest Holy Scripture be exposed to the ridicule of unbelievers, and obstacles be placed to their believing." (Summa 1a, 68, 1)
where the referenced text from Augustine of Hippo reads:
"In matters that are obscure and far beyond our vision, even in such as we may find treated in Holy Scripture, different interpretations are sometimes possible without prejudice to the faith we have received. In such a case, we should not rush in headlong and so firmly take our stand on one side that, if further progress in the search of truth justly undermines this position, we too fall with it. That would be to battle not for the teaching of Holy Scripture but for our own, wishing its teaching to conform to ours, whereas we ought to wish ours to conform to that of Sacred Scripture." (Gen. ad lit. i, 18)
In medieval universities, the faculty for natural philosophy and theology were separate, and discussions pertaining to theological issues were often not allowed to be undertaken by the faculty of philosophy. Natural philosophy, as taught in the arts faculties of the universities, was seen as an essential area of study in its own right and was considered necessary for almost every area of study. It was an independent field, separated from theology, and enjoyed a good deal of intellectual freedom as long as it was restricted to the natural world. In general, there was religious support for natural science by the late Middle Ages and a recognition that it was an important element of learning.
The extent to which medieval science led directly to the new philosophy of the scientific revolution remains a subject for debate, but it certainly had a significant influence.
The Middle Ages laid ground for the developments that took place in science, during the Renaissance which immediately succeeded it. By 1630, ancient authority from classical literature and philosophy, as well as their necessity, started eroding, although scientists were still expected to be fluent in Latin, the international language of Europe's intellectuals. With the sheer success of science and the steady advance of rationalism, the individual scientist gained prestige. Along with the inventions of this period, especially the printing press by Johannes Gutenberg, allowing for the dissemination of the Bible in vernacular languages. This allowed more people to read and learn from the scripture, leading to the Evangelical movement. The people who spread this message concentrated more on individual agency rather than the structures of the Church.
==== Medieval Contributors ====
Some medieval contributors to science included: Boethius (c. 477–524), John Philoponus (c. 490–570), Bede the Venerable (c. 672–735), Alcuin of York (c. 735–804), Leo the Mathematician (c. 790–869), Gerbert of Aurillac (c. 946–1003), Constantine the African (c. 1020–1087), Adelard of Bath (c. 1080–1152), Robert Grosseteste (c. 1168–1253), St. Albert the Great (c. 1200–1280), Roger Bacon (c. 1214–1294), William of Ockham (c. 1287–1347), Jean Burdian (c. 1301–1358), Thomas Bradwardine (1300–1349), Nicole Oresme (c. 1320–1382), Nicholas of Cusa (c. 1401–1464).
=== Modern period ===
In the 17th century, founders of the Royal Society largely held conventional and orthodox religious views, and a number of them were prominent Churchmen. While theological issues that had the potential to be divisive were typically excluded from formal discussions of the early Society, many of its fellows nonetheless believed that their scientific activities provided support for traditional religious belief. Clerical involvement in the Royal Society remained high until the mid-nineteenth century when science became more professionalized.
Albert Einstein supported the compatibility of some interpretations of religion with science. In "Science, Philosophy and Religion, A Symposium" published by the Conference on Science, Philosophy and Religion in Their Relation to the Democratic Way of Life, Inc., New York in 1941, Einstein stated:
Accordingly, a religious person is devout in the sense that he has no doubt of the significance and loftiness of those superpersonal objects and goals which neither require nor are capable of rational foundation. They exist with the same necessity and matter-of-factness as he himself. In this sense religion is the age-old endeavor of mankind to become clearly and completely conscious of these values and goals and constantly to strengthen and extend their effect. If one conceives of religion and science according to these definitions then a conflict between them appears impossible. For science can only ascertain what is, but not what should be, and outside of its domain value judgments of all kinds remain necessary. Religion, on the other hand, deals only with evaluations of human thought and action: it cannot justifiably speak of facts and relationships between facts. According to this interpretation the well-known conflicts between religion and science in the past must all be ascribed to a misapprehension of the situation which has been described.
Einstein thus expresses views of ethical non-naturalism (contrasted to ethical naturalism).
Prominent modern scientists who are atheists include evolutionary biologist Richard Dawkins and Nobel Prize–winning physicist Steven Weinberg. Prominent scientists advocating religious belief include Nobel Prize–winning physicist and United Church of Christ member Charles Townes, evangelical Christian and past head of the Human Genome Project Francis Collins, and climatologist John T. Houghton.
== Perspectives ==
The kinds of interactions that might arise between science and religion have been categorized by theologian, Anglican priest, and physicist John Polkinghorne: (1) conflict between the disciplines, (2) independence of the disciplines, (3) dialogue between the disciplines where they overlap and (4) integration of both into one field.
This typology is similar to ones used by theologians Ian Barbour and John Haught. More typologies that categorize this relationship can be found among the works of other science and religion scholars such as theologian and biochemist Arthur Peacocke.
=== Incompatibility ===
According to Guillermo Paz-y-Miño-C and Avelina Espinosa, the historical conflict between evolution and religion is intrinsic to the incompatibility between scientific rationalism/empiricism and the belief in supernatural causation/faith. According to evolutionary biologist Jerry Coyne, views on evolution and levels of religiosity in some countries, along with the existence of books explaining reconciliation between evolution and religion, indicate that people have trouble in believing both at the same time, thus implying incompatibility. According to physical chemist Peter Atkins, "whereas religion scorns the power of human comprehension, science respects it." Planetary scientist Carolyn Porco describes a hope that "the confrontation between science and formal religion will come to an end when the role played by science in the lives of all people is the same played by religion today."
Geologist and paleontologist Donald Prothero has stated that religion is the reason "questions about evolution, the age of the earth, cosmology, and human evolution nearly always cause Americans to flunk science literacy tests compared to other nations." However, Jon Miller, who studies science literacy across nations, states that Americans in general are slightly more scientifically literate than Europeans and the Japanese.
According to cosmologist and astrophysicist Lawrence Krauss, compatibility or incompatibility is a theological concern, not a scientific concern. In Lisa Randall's view, questions of incompatibility or otherwise are not answerable, since by accepting revelations one is abandoning rules of logic which are needed to identify if there are indeed contradictions between holding certain beliefs. Daniel Dennett holds that incompatibility exists because religion is not problematic to a certain point before it collapses into a number of excuses for keeping certain beliefs, in light of evolutionary implications.
According to theoretical physicist Steven Weinberg, teaching cosmology and evolution to students should decrease their self-importance in the universe, as well as their religiosity. Evolutionary developmental biologist PZ Myers' view is that all scientists should be atheists, and that science should never accommodate any religious beliefs. Physicist Sean M. Carroll claims that since religion makes claims that are supernatural, both science and religion are incompatible.
Evolutionary biologist Richard Dawkins is openly hostile to religion because he believes it actively debauches the scientific enterprise and education involving science. According to Dawkins, religion "subverts science and saps the intellect". He believes that when science teachers attempt to expound on evolution, there is hostility aimed towards them by parents who are skeptical because they believe it conflicts with their own religious beliefs, and that even in some textbooks have had the word 'evolution' systematically removed. He has worked to argue the negative effects that he believes religion has on education of science.
According to Renny Thomas' study on Indian scientists, atheistic scientists in India called themselves atheists even while accepting that their lifestyle is very much a part of tradition and religion. Thus, they differ from Western atheists in that for them following the lifestyle of a religion is not antithetical to atheism.
==== Criticism ====
Others such as Francis Collins, George F. R. Ellis, Kenneth R. Miller, Katharine Hayhoe, George Coyne and Simon Conway Morris argue for compatibility since they do not agree that science is incompatible with religion and vice versa. They argue that science provides many opportunities to look for and find God in nature and to reflect on their beliefs. According to Kenneth Miller, he disagrees with Jerry Coyne's assessment and argues that since significant portions of scientists are religious and the proportion of Americans believing in evolution is much higher, it implies that both are indeed compatible. Elsewhere, Miller has argued that when scientists make claims on science and theism or atheism, they are not arguing scientifically at all and are stepping beyond the scope of science into discourses of meaning and purpose. What he finds particularly odd and unjustified is in how atheists often come to invoke scientific authority on their non-scientific philosophical conclusions like there being no point or no meaning to the universe as the only viable option when the scientific method and science never have had any way of addressing questions of meaning or God in the first place. Furthermore, he notes that since evolution made the brain and since the brain can handle both religion and science, there is no natural incompatibility between the concepts at the biological level.
Karl Giberson argues that when discussing compatibility, some scientific intellectuals often ignore the viewpoints of intellectual leaders in theology and instead argue against less informed masses, thereby, defining religion by non-intellectuals and slanting the debate unjustly. He argues that leaders in science sometimes trump older scientific baggage and that leaders in theology do the same, so once theological intellectuals are taken into account, people who represent extreme positions like Ken Ham and Eugenie Scott will become irrelevant. Cynthia Tolman notes that religion does not have a method per se partly because religions emerge through time from diverse cultures, but when it comes to Christian theology and ultimate truths, she notes that people often rely on scripture, tradition, reason, and experience to test and gauge what they experience and what they should believe.
==== Conflict thesis ====
The conflict thesis, which holds that religion and science have been in conflict continuously throughout history, was popularized in the 19th century by John William Draper's and Andrew Dickson White's accounts. It was in the 19th century that relationship between science and religion became an actual formal topic of discourse, while before this no one had pitted science against religion or vice versa, though occasional complex interactions had been expressed before the 19th century. Most contemporary historians of science now reject the conflict thesis in its original form and no longer support it. Instead, it has been superseded by subsequent historical research which has resulted in a more nuanced understanding. Historian of science, Gary Ferngren, has stated: "Although popular images of controversy continue to exemplify the supposed hostility of Christianity to new scientific theories, studies have shown that Christianity has often nurtured and encouraged scientific endeavour, while at other times the two have co-existed without either tension or attempts at harmonization. If Galileo and the Scopes trial come to mind as examples of conflict, they were the exceptions rather than the rule."
Most historians today have moved away from a conflict model, which is based mainly on two historical episodes (Galileo and Darwin), toward compatibility theses (either the integration thesis or non-overlapping magisteria) or toward a "complexity" model, because religious figures were on both sides of each dispute and there was no overall aim by any party involved to discredit religion.
An often cited example of conflict, that has been clarified by historical research in the 20th century, was the Galileo affair, whereby interpretations of the Bible were used to attack ideas by Copernicus on heliocentrism. By 1616 Galileo went to Rome to try to persuade Catholic Church authorities not to ban Copernicus' ideas. In the end, a decree of the Congregation of the Index was issued, declaring that the ideas that the Sun stood still and that the Earth moved were "false" and "altogether contrary to Holy Scripture", and suspending Copernicus's De Revolutionibus until it could be corrected. Galileo was found "vehemently suspect of heresy", namely of having held the opinions that the Sun lies motionless at the center of the universe, that the Earth is not at its centre and moves. He was required to "abjure, curse and detest" those opinions. However, before all this, Pope Urban VIII had personally asked Galileo to give arguments for and against heliocentrism in a book, and to be careful not to advocate heliocentrism as physically proven since the scientific consensus at the time was that the evidence for heliocentrism was very weak. The Church had merely sided with the scientific consensus of the time. Pope Urban VIII asked that his own views on the matter be included in Galileo's book. Only the latter was fulfilled by Galileo. Whether unknowingly or deliberately, Simplicio, the defender of the Aristotelian/Ptolemaic geocentric view in Dialogue Concerning the Two Chief World Systems, was often portrayed as an unlearned fool who lacked mathematical training. Although the preface of his book claims that the character is named after a famous Aristotelian philosopher (Simplicius in Latin, Simplicio in Italian), the name "Simplicio" in Italian also has the connotation of "simpleton". Unfortunately for his relationship with the Pope, Galileo put the words of Urban VIII into the mouth of Simplicio. Most historians agree Galileo did not act out of malice and felt blindsided by the reaction to his book. However, the Pope did not take the suspected public ridicule lightly, nor the physical Copernican advocacy. Galileo had alienated one of his biggest and most powerful supporters, the Pope, and was called to Rome to defend his writings.
The actual evidences that finally proved heliocentrism came centuries after Galileo: the stellar aberration of light by James Bradley in the 18th century, the orbital motions of binary stars by William Herschel in the 19th century, the accurate measurement of the stellar parallax in the 19th century, and Newtonian mechanics in the 17th century. According to physicist Christopher Graney, Galileo's own observations did not actually support the Copernican view, but were more consistent with Tycho Brahe's hybrid model where that Earth did not move and everything else circled around it and the Sun.
British philosopher A. C. Grayling, still believes there is competition between science and religions in areas related to the origin of the universe, the nature of human beings and the possibility of miracles.
=== Independence ===
A modern view, described by Stephen Jay Gould as "non-overlapping magisteria" (NOMA), is that science and religion deal with fundamentally separate aspects of human experience and so, when each stays within its own domain, they co-exist peacefully. While Gould spoke of independence from the perspective of science, W. T. Stace viewed independence from the perspective of the philosophy of religion. Stace felt that science and religion, when each is viewed in its own domain, are both consistent and complete. They originate from different perceptions of reality, as Arnold O. Benz points out, but meet each other, for example, in the feeling of amazement and in ethics.
The USA's National Academy of Sciences supports the view that science and religion are independent.
Science and religion are based on different aspects of human experience. In science, explanations must be based on evidence drawn from examining the natural world. Scientifically based observations or experiments that conflict with an explanation eventually must lead to modification or even abandonment of that explanation. Religious faith, in contrast, does not depend on empirical evidence, is not necessarily modified in the face of conflicting evidence, and typically involves supernatural forces or entities. Because they are not a part of nature, supernatural entities cannot be investigated by science. In this sense, science and religion are separate and address aspects of human understanding in different ways. Attempts to put science and religion against each other create controversy where none needs to exist.
According to Archbishop John Habgood, both science and religion represent distinct ways of approaching experience and these differences are sources of debate. He views science as descriptive and religion as prescriptive. He stated that if science and mathematics concentrate on what the world ought to be, in the way that religion does, it may lead to improperly ascribing properties to the natural world as happened among the followers of Pythagoras in the sixth century B.C. In contrast, proponents of a normative moral science take issue with the idea that science has no way of guiding "oughts". Habgood also stated that he believed that the reverse situation, where religion attempts to be descriptive, can also lead to inappropriately assigning properties to the natural world. A notable example is the now defunct belief in the Ptolemaic (geocentric) planetary model that held sway until changes in scientific and religious thinking were brought about by Galileo and proponents of his views.
In the view of the Lubavitcher rabbi Menachem Mendel Schneerson, non-Euclidean geometry such as Lobachevsky's hyperbolic geometry and Riemann's elliptic geometry proved that Euclid's axioms, such as, "there is only one straight line between two points", are in fact arbitrary. Therefore, science, which relies on arbitrary axioms, can never refute Torah, which is absolute truth.
==== Parallels in method ====
According to Ian Barbour, Thomas S. Kuhn asserted that science is made up of paradigms that arise from cultural traditions, which is similar to the secular perspective on religion.
Michael Polanyi asserted that it is merely a commitment to universality that protects against subjectivity and has nothing at all to do with personal detachment as found in many conceptions of the scientific method. Polanyi further asserted that all knowledge is personal and therefore the scientist must be performing a very personal if not necessarily subjective role when doing science. Polanyi added that the scientist often merely follows intuitions of "intellectual beauty, symmetry, and 'empirical agreement'". Polanyi held that science requires moral commitments similar to those found in religion.
Two physicists, Charles A. Coulson and Harold K. Schilling, both claimed that "the methods of science and religion have much in common." Schilling asserted that both fields—science and religion—have "a threefold structure—of experience, theoretical interpretation, and practical application." Coulson asserted that science, like religion, "advances by creative imagination" and not by "mere collecting of facts," while stating that religion should and does "involve critical reflection on experience not unlike that which goes on in science." Religious language and scientific language also show parallels (cf. rhetoric of science).
=== Dialogue ===
The religion and science community consists of those scholars who involve themselves with what has been called the "religion-and-science dialogue" or the "religion-and-science field." The community belongs to neither the scientific nor the religious community, but is said to be a third overlapping community of interested and involved scientists, priests, clergymen, theologians and engaged non-professionals. Institutions interested in the intersection between science and religion include the Center for Theology and the Natural Sciences, the Institute on Religion in an Age of Science, the Ian Ramsey Centre, and the Faraday Institute. Journals addressing the relationship between science and religion include Theology and Science and Zygon. Eugenie Scott has written that the "science and religion" movement is, overall, composed mainly of theists who have a healthy respect for science and may be beneficial to the public understanding of science. She contends that the "Christian scholarship" movement is not a problem for science, but that the "Theistic science" movement, which proposes abandoning methodological materialism, does cause problems in understanding of the nature of science. The Gifford Lectures were established in 1885 to further the discussion between "natural theology" and the scientific community. This annual series continues and has included William James, John Dewey, Carl Sagan, and many other professors from various fields.
The modern dialogue between religion and science is rooted in Ian Barbour's 1966 book Issues in Science and Religion. Since that time it has grown into a serious academic field, with academic chairs in the subject area, and two dedicated academic journals, Zygon and Theology and Science. Articles are also sometimes found in mainstream science journals such as American Journal of Physics
and Science.
Philosopher Alvin Plantinga has argued that there is superficial conflict but deep concord between science and religion, and that there is deep conflict between science and naturalism. Plantinga, in his book Where the Conflict Really Lies: Science, Religion, and Naturalism, heavily contests the linkage of naturalism with science, as conceived by Richard Dawkins, Daniel Dennett and like-minded thinkers; while Daniel Dennett thinks that Plantinga stretches science to an unacceptable extent. Philosopher Maarten Boudry, in reviewing the book, has commented that he resorts to creationism and fails to "stave off the conflict between theism and evolution." Cognitive scientist Justin L. Barrett, by contrast, reviews the same book and writes that "those most needing to hear Plantinga's message may fail to give it a fair hearing for rhetorical rather than analytical reasons."
=== Integration ===
As a general view, this holds that while interactions are complex between influences of science, theology, politics, social, and economic concerns, the productive engagements between science and religion throughout history should be duly stressed as the norm.
Scientific and theological perspectives often coexist peacefully. Christians and some non-Christian religions have historically integrated well with scientific ideas, as in the ancient Egyptian technological mastery applied to monotheistic ends, the scientific advances made by Muslim scholars during the Ottoman Empire and mathematics under Hinduism and Buddhism. Even many 19th-century Christian communities welcomed scientists who claimed that science was not at all concerned with discovering the ultimate nature of reality. According to Lawrence M. Principe, the Johns Hopkins University Drew Professor of the Humanities, from a historical perspective this points out that much of the current-day clashes occur between limited extremists—both religious and scientistic fundamentalists—over a very few topics, and that the movement of ideas back and forth between scientific and theological thought has been more usual. To Principe, this perspective would point to the fundamentally common respect for written learning in religious traditions of rabbinical literature, Christian theology, and the Islamic Golden Age, including a Transmission of the Classics from Greek to Islamic to Christian traditions which helped spark the Renaissance. Religions have also given key participation in development of modern universities and libraries; centers of learning & scholarship were coincident with religious institutions—whether pagan, Muslim, or Christian.
== Individual religions ==
=== Baháʼí Faith ===
A fundamental principle of the Baháʼí Faith is the harmony of religion and science. Baháʼí scripture asserts that true science and true religion can never be in conflict. `Abdu'l-Bahá, the son of the founder of the religion, stated that religion without science is superstition and that science without religion is materialism. He also admonished that true religion must conform to the conclusions of science.
=== Buddhism ===
Buddhism and science have been regarded as compatible by numerous authors. Some philosophic and psychological teachings found in Buddhism share points in common with modern Western scientific and philosophic thought. For example, Buddhism encourages the impartial investigation of nature (an activity referred to as Dhamma-Vicaya in the Pali Canon)—the principal object of study being oneself. Buddhism and science both show a strong emphasis on causality. However, Buddhism does not focus on materialism.
Tenzin Gyatso, the 14th Dalai Lama, mentions that empirical scientific evidence supersedes the traditional teachings of Buddhism when the two are in conflict. In his book The Universe in a Single Atom he wrote, "My confidence in venturing into science lies in my basic belief that as in science, so in Buddhism, understanding the nature of reality is pursued by means of critical investigation." He also stated, "If scientific analysis were conclusively to demonstrate certain claims in Buddhism to be false," he says, "then we must accept the findings of science and abandon those claims."
=== Christianity ===
Among early Christian teachers, Tertullian (c. 160–220) held a generally negative opinion of Greek philosophy, while Origen (c. 185–254) regarded it much more favorably and required his students to read nearly every work available to them.
Earlier attempts at reconciliation of Christianity with Newtonian mechanics appear quite different from later attempts at reconciliation with the newer scientific ideas of evolution or relativity. Many early interpretations of evolution polarized themselves around a struggle for existence. These ideas were significantly countered by later findings of universal patterns of biological cooperation. According to John Habgood, the universe seems to be a mix of good and evil, beauty and pain, and that suffering may somehow be part of the process of creation. Habgood holds that Christians should not be surprised that suffering may be used creatively by God, given their faith in the symbol of the Cross.
Robert John Russell has examined consonance and dissonance between modern physics, evolutionary biology, and Christian theology.
Christian philosophers Augustine of Hippo (354–430) and Thomas Aquinas (1225–1274) held that scriptures can have multiple interpretations on certain areas where the matters were far beyond their reach, therefore one should leave room for future findings to shed light on the meanings. The "Handmaiden" tradition, which saw secular studies of the universe as a very important and helpful part of arriving at a better understanding of scripture, was adopted throughout Christian history from early on. Also the sense that God created the world as a self operating system is what motivated many Christians throughout the Middle Ages to investigate nature.
Modern historians of science such as J.L. Heilbron, Alistair Cameron Crombie, David Lindberg, Edward Grant, Thomas Goldstein, and Ted Davis have reviewed the popular notion that medieval Christianity was a negative influence in the development of civilization and science. In their views, not only did the monks save and cultivate the remnants of ancient civilization during the barbarian invasions, but the medieval church promoted learning and science through its sponsorship of many universities which, under its leadership, grew rapidly in Europe in the 11th and 12th centuries. Saint Thomas Aquinas, the Church's "model theologian", not only argued that reason is in harmony with faith, he even recognized that reason can contribute to understanding revelation, and so encouraged intellectual development. He was not unlike other medieval theologians who sought out reason in the effort to defend his faith. Some modern scholars, such as Stanley Jaki, have claimed that Christianity with its particular worldview, was a crucial factor for the emergence of modern science.
David C. Lindberg states that the widespread popular belief that the Middle Ages was a time of ignorance and superstition due to the Christian church is a "caricature". According to Lindberg, while there are some portions of the classical tradition which suggest this view, these were exceptional cases. It was common to tolerate and encourage critical thinking about the nature of the world. The relation between Christianity and science is complex and cannot be simplified to either harmony or conflict, according to Lindberg. Lindberg reports that "the late medieval scholar rarely experienced the coercive power of the church and would have regarded himself as free (particularly in the natural sciences) to follow reason and observation wherever they led. There was no warfare between science and the church." Ted Peters in Encyclopedia of Religion writes that although there is some truth in the "Galileo's condemnation" story but through exaggerations, it has now become "a modern myth perpetuated by those wishing to see warfare between science and religion who were allegedly persecuted by an atavistic and dogma-bound ecclesiastical authority". In 1992, the Catholic Church's seeming vindication of Galileo attracted much comment in the media.
A degree of concord between science and religion can be seen in religious belief and empirical science. The belief that God created the world and therefore humans, can lead to the view that he arranged for humans to know the world. This is underwritten by the doctrine of imago dei. In the words of Thomas Aquinas, "Since human beings are said to be in the image of God in virtue of their having a nature that includes an intellect, such a nature is most in the image of God in virtue of being most able to imitate God".
During the Enlightenment, a period "characterized by dramatic revolutions in science" and the rise of Protestant challenges to the authority of the Catholic Church via individual liberty, the authority of Christian scriptures became strongly challenged. As science advanced, acceptance of a literal version of the Bible became "increasingly untenable" and some in that period presented ways of interpreting scripture according to its spirit on its authority and truth.
After the Black Death in Europe, there occurred a generalized decrease in faith in the Catholic Church. The "Natural Sciences" during the Medieval Era focused largely on scientific arguments. The Copernicans, who were generally a small group of privately sponsored individuals, who were deemed Heretics by the Church in some instances. Copernicus and his work challenged the view held by the Catholic Church and the common scientific view at the time, yet according to scholar J. L. Heilbron, the Roman Catholic Church sometimes provided financial support to the Copernicans. In doing so, the Church did support and promote scientific research when the goals in question were in alignment with those of the faith, so long as the findings were in line with the rhetoric of the Church. A case example is the Catholic need for an accurate calendar. Calendar reform was a touchy subject: civilians doubted the accuracy of the mathematics and were upset that the process unfairly selected curators of the reform. The Roman Catholic Church needed a precise date for the Easter Sabbath, and thus the Church was highly supportive of calendar reform. The need for the correct date of Easter was also the impetus of cathedral construction. Cathedrals essentially functioned as massive scale sun dials and, in some cases, camera obscuras. They were efficient scientific devices because they rose high enough for their naves to determine the summer and winter solstices. Heilbron contends that as far back as the twelfth century, the Roman Catholic Church was funding scientific discovery and the recovery of ancient Greek scientific texts. However, the Copernican revolution challenged the view held the Catholic Church and placed the Sun at the center of the Solar System.
==== Perspectives on evolution ====
In recent history, the theory of evolution has been at the center of some controversy between Christianity and science. Christians who accept a literal interpretation of the biblical account of creation find incompatibility between Darwinian evolution and their interpretation of the Christian faith. Creation science or scientific creationism is a branch of creationism that attempts to provide scientific support for a literal reading of the Genesis creation narrative in the Book of Genesis and attempts to disprove generally accepted scientific facts, theories and scientific paradigms about the geological history of the Earth, cosmology of the early universe,
the chemical origins of life and biological evolution. It began in the 1960s as a fundamentalist Christian effort in the United States to prove Biblical inerrancy and falsify the scientific evidence for evolution. It has since developed a sizable religious following in the United States, with creation science ministries branching worldwide. In 1925, The State of Tennessee passed the Butler Act, which prohibited the teaching of the theory of evolution in all schools in the state. Later that year, a similar law was passed in Mississippi, and likewise, Arkansas in 1927. In 1968, these "anti-monkey" laws were struck down by the Supreme Court of the United States as unconstitutional, "because they established a religious doctrine violating both the First and Fourth Amendments to the Constitution."
Most scientists have rejected creation science for several reasons, including that its claims do not refer to natural causes and cannot be tested. In 1987, the United States Supreme Court ruled that creationism is religion, not science, and cannot be advocated in public school classrooms. In 2018, the Orlando Sentinel reported that "Some private schools in Florida that rely on public funding teach students" Creationism.
Theistic evolution attempts to reconcile Christian beliefs and science by accepting the scientific understanding of the age of the Earth and the process of evolution. It includes a range of beliefs, including views described as evolutionary creationism, which accepts some findings of modern science but also upholds classical religious teachings about God and creation in Christian context.
==== Roman Catholicism ====
While refined and clarified over the centuries, the Roman Catholic position on the relationship between science and religion is one of harmony, and has maintained the teaching of natural law as set forth by Thomas Aquinas. For example, regarding scientific study such as that of evolution, the church's unofficial position is an example of theistic evolution, stating that faith and scientific findings regarding human evolution are not in conflict, though humans are regarded as a special creation, and that the existence of God is required to explain both monogenism and the spiritual component of human origins. Catholic schools have included all manners of scientific study in their curriculum for many centuries.
Galileo once stated that "The intention of the Holy Spirit is to teach us how to go to heaven, not how the heavens go." In 1981, Pope John Paul II, then leader of the Roman Catholic Church, spoke of the relationship this way: "The Bible itself speaks to us of the origin of the universe and its make-up, not in order to provide us with a scientific treatise, but in order to state the correct relationships of man with God and with the universe. Sacred Scripture wishes simply to declare that the world was created by God, and in order to teach this truth it expresses itself in the terms of the cosmology in use at the time of the writer".
Pope Francis, in his encyclical letter Laudato si', affirms his opinion that "science and religion, with their distinctive approaches to understanding reality, can
enter into an intense dialogue fruitful for both".
==== Influence of a biblical worldview on early modern science ====
According to Andrew Dickson White's A History of the Warfare of Science with Theology in Christendom from the 19th century, a biblical world view affected negatively the progress of science through time. Dickinson also argues that immediately following the Reformation matters were even worse. The interpretations of Scripture by Luther and Calvin became as sacred to their followers as the Scripture itself. For instance, when Georg Calixtus ventured, in interpreting the Psalms, to question the accepted belief that "the waters above the heavens" were contained in a vast receptacle upheld by a solid vault, he was bitterly denounced as heretical. Today, much of the scholarship in which the conflict thesis was originally based is considered to be inaccurate. For instance, the claim that early Christians rejected scientific findings by the Greco-Romans is false, since the "handmaiden" view of secular studies was seen to shed light on theology. This view was widely adapted throughout the early medieval period and afterwards by theologians (such as Augustine) and ultimately resulted in fostering interest in knowledge about nature through time. Also, the claim that people of the Middle Ages widely believed that the Earth was flat was first propagated in the same period that originated the conflict thesis and is still very common in popular culture. Modern scholars regard this claim as mistaken, as the contemporary historians of science David C. Lindberg and Ronald L. Numbers write: "there was scarcely a Christian scholar of the Middle Ages who did not acknowledge [earth's] sphericity and even know its approximate circumference." From the fall of Rome to the time of Columbus, all major scholars and many vernacular writers interested in the physical shape of the earth held a spherical view with the exception of Lactantius and Cosmas.
H. Floris Cohen argued for a biblical Protestant, but not excluding Catholicism, influence on the early development of modern science. He presented Dutch historian R. Hooykaas' argument that a biblical world-view holds all the necessary antidotes for the hubris of Greek rationalism: a respect for manual labour, leading to more experimentation and empiricism, and a supreme God that left nature open to emulation and manipulation. It supports the idea early modern science rose due to a combination of Greek and biblical thought.
Oxford historian Peter Harrison is another who has argued that a biblical worldview was significant for the development of modern science. Harrison contends that Protestant approaches to the book of scripture had significant, if largely unintended, consequences for the interpretation of the book of nature. Harrison has also suggested that literal readings of the Genesis narratives of the Creation and Fall motivated and legitimated scientific activity in seventeenth-century England. For many of its seventeenth-century practitioners, science was imagined to be a means of restoring a human dominion over nature that had been lost as a consequence of the Fall.
Historian and professor of religion Eugene M. Klaaren holds that "a belief in divine creation" was central to an emergence of science in seventeenth-century England. The philosopher Michael Foster has published analytical philosophy connecting Christian doctrines of creation with empiricism. Historian William B. Ashworth has argued against the historical notion of distinctive mind-sets and the idea of Catholic and Protestant sciences. Historians James R. Jacob and Margaret C. Jacob have argued for a linkage between seventeenth-century Anglican intellectual transformations and influential English scientists (e.g., Robert Boyle and Isaac Newton). John Dillenberger and Christopher B. Kaiser have written theological surveys, which also cover additional interactions occurring in the 18th, 19th, and 20th centuries. Philosopher of Religion, Richard Jones, has written a philosophical critique of the "dependency thesis" which assumes that modern science emerged from Christian sources and doctrines. Though he acknowledges that modern science emerged in a religious framework, that Christianity greatly elevated the importance of science by sanctioning and religiously legitimizing it in the medieval period, and that Christianity created a favorable social context for it to grow; he argues that direct Christian beliefs or doctrines were not primary sources of scientific pursuits by natural philosophers, nor was Christianity, in and of itself, exclusively or directly necessary in developing or practicing modern science.
Oxford University historian and theologian John Hedley Brooke wrote that "when natural philosophers referred to laws of nature, they were not glibly choosing that metaphor. Laws were the result of legislation by an intelligent deity. Thus the philosopher René Descartes (1596–1650) insisted that he was discovering the "laws that God has put into nature." Later Newton would declare that the regulation of the solar system presupposed the "counsel and dominion of an intelligent and powerful Being." Historian Ronald L. Numbers stated that this thesis "received a boost" from mathematician and philosopher Alfred North Whitehead's Science and the Modern World (1925). Numbers has also argued, "Despite the manifest shortcomings of the claim that Christianity gave birth to science—most glaringly, it ignores or minimizes the contributions of ancient Greeks and medieval Muslims—it too, refuses to succumb to the death it deserves." The sociologist Rodney Stark of Baylor University, argued in contrast that "Christian theology was essential for the rise of science."
Protestantism had an important influence on science. According to the Merton Thesis there was a positive correlation between the rise of Puritanism and Protestant Pietism on the one hand and early experimental science on the other. The Merton Thesis has two separate parts: Firstly, it presents a theory that science changes due to an accumulation of observations and improvement in experimental techniques and methodology; secondly, it puts forward the argument that the popularity of science in 17th-century England and the religious demography of the Royal Society (English scientists of that time were predominantly Puritans or other Protestants) can be explained by a correlation between Protestantism and the scientific values. In his theory, Robert K. Merton focused on English Puritanism and German Pietism as having been responsible for the development of the scientific revolution of the 17th and 18th centuries. Merton explained that the connection between religious affiliation and interest in science was the result of a significant synergy between the ascetic Protestant values and those of modern science. Protestant values encouraged scientific research by allowing science to study God's influence on the world and thus providing a religious justification for scientific research.
Some scholars have noted a direct tie between "particular aspects of traditional Christianity" and the rise of science. Other scholars and historians attribute Christianity to having contributed to the rise of the Scientific Revolution.
==== Reconciliation in Britain in the early 20th century ====
In Reconciling Science and Religion: The Debate in Early-twentieth-century Britain, historian of biology Peter J. Bowler argues that in contrast to the conflicts between science and religion in the U.S. in the 1920s (most famously the Scopes Trial), during this period Great Britain experienced a concerted effort at reconciliation, championed by intellectually conservative scientists, supported by liberal theologians but opposed by younger scientists and secularists and conservative Christians. These attempts at reconciliation fell apart in the 1930s due to increased social tensions, moves towards neo-orthodox theology and the acceptance of the modern evolutionary synthesis.
In the 20th century, several ecumenical organizations promoting a harmony between science and Christianity were founded, most notably the American Scientific Affiliation, The Biologos Foundation, Christians in Science, The Society of Ordained Scientists, and The Veritas Forum.
=== Confucianism and traditional Chinese religion ===
The historical process of Confucianism has largely been antipathic towards scientific discovery. However the religio-philosophical system itself is more neutral on the subject than such an analysis might suggest. In his writings On Heaven, Xunzi espoused a proto-scientific world view. However, during the Han Synthesis the more anti-empirical Mencius was favored and combined with Daoist skepticism regarding the nature of reality. Likewise, during the medieval period, Zhu Xi argued against technical investigation and specialization proposed by Chen Liang. After contact with the West, scholars such as Wang Fuzhi would rely on Buddhist/Daoist skepticism to denounce all science as a subjective pursuit limited by humanity's fundamental ignorance of the true nature of the world.
The Jesuits from Europe taught Western math and science to the Chinese bureaucrats in hopes of religious conversion. This process saw several challenges of both European and Chinese spiritual and scientific beliefs. The keynote text of Chinese scientific philosophy, The Book of Changes (or Yi Jing) was initially mocked and disregarded by the Westerners. In return, Confucian scholars Dai Zhen and Ji Yun found the concept of phantoms laughable and ridiculous. The Book of Changes outlined orthodoxy cosmology in the Qing, including yin and yang and the five cosmic phases. Sometimes the missionary exploits proved dangerous for the Westerners. Jesuit missionaries and scholars Ferdinand Vervbiest and Adam Schall were punished after using scientific methods to determine the exact time of the 1664 eclipse. However, the European mission eastward did not only cause conflict. Joachim Bouvet, a theologian who held equal respect for both the Bible and the Book of Changes, was productive in his mission of spreading the Christian faith.
After the May Fourth Movement, attempts to modernize Confucianism and reconcile it with scientific understanding were attempted by many scholars including Feng Youlan and Xiong Shili. Given the close relationship that Confucianism shares with Buddhism, many of the same arguments used to reconcile Buddhism with science also readily translate to Confucianism. However, modern scholars have also attempted to define the relationship between science and Confucianism on Confucianism's own terms and the results have usually led to the conclusion that Confucianism and science are fundamentally compatible.
=== Hinduism ===
In Hinduism, the dividing line between objective sciences and spiritual knowledge (adhyatma vidya) is a linguistic paradox. Hindu scholastic activities and ancient Indian scientific advancements were so interconnected that many Hindu scriptures are also ancient scientific manuals and vice versa. In 1835, English was made the primary language for teaching in higher education in India, exposing Hindu scholars to Western secular ideas; this started a renaissance regarding religious and philosophical thought. Hindu sages maintained that logical argument and rational proof using Nyaya is the way to obtain correct knowledge. The scientific level of understanding focuses on how things work and from where they originate, while Hinduism strives to understand the ultimate purposes for the existence of living things. To obtain and broaden the knowledge of the world for spiritual perfection, many refer to the Bhāgavata for guidance because it draws upon a scientific and theological dialogue. Hinduism offers methods to correct and transform itself in course of time. For instance, Hindu views on the development of life include a range of viewpoints in regards to evolution, creationism, and the origin of life within the traditions of Hinduism. For instance, it has been suggested that Wallace-Darwininan evolutionary thought was a part of Hindu thought centuries before modern times. The Shankara and the Sāmkhya did not have a problem with the theory of evolution, but instead, argued about the existence of God and what happened after death. These two distinct groups argued among each other's philosophies because of their texts, not the idea of evolution. With the publication of Darwin's On the Origin of Species, many Hindus were eager to connect their scriptures to Darwinism, finding similarities between Brahma's creation, Vishnu's incarnations, and evolution theories.
Samkhya, the oldest school of Hindu philosophy prescribes a particular method to analyze knowledge. According to Samkhya, all knowledge is possible through three means of valid knowledge –
Pratyakṣa or Dṛṣṭam – direct sense perception,
Anumāna – logical inference and
Śabda or Āptavacana – verbal testimony.
Nyaya, the Hindu school of logic, accepts all these 3 means and in addition accepts one more – Upamāna (comparison).
The accounts of the emergence of life within the universe vary in description, but classically the deity called Brahma, from a Trimurti of three deities also including Vishnu and Shiva, is described as performing the act of 'creation', or more specifically of 'propagating life within the universe' with the other two deities being responsible for 'preservation' and 'destruction' (of the universe) respectively. In this respect some Hindu schools do not treat the scriptural creation myth literally and often the creation stories themselves do not go into specific detail, thus leaving open the possibility of incorporating at least some theories in support of evolution. Some Hindus find support for, or foreshadowing of evolutionary ideas in scriptures, namely the Vedas.
The incarnations of Vishnu (Dashavatara) is almost identical to the scientific explanation of the sequence of biological evolution of man and animals. The sequence of avatars starts from an aquatic organism (Matsya), to an amphibian (Kurma), to a land-animal (Varaha), to a humanoid (Narasimha), to a dwarf human (Vamana), to 5 forms of well developed human beings (Parashurama, Rama, Balarama/Buddha, Krishna, Kalki) who showcase an increasing form of complexity (Axe-man, King, Plougher/Sage, wise Statesman, mighty Warrior). In fact, many Hindu gods are represented with features of animals as well as those of humans, leading many Hindus to easily accept evolutionary links between animals and humans. In India, the home country of Hindus, educated Hindus widely accept the theory of biological evolution. In a survey of 909 people, 77% of respondents in India agreed with Charles Darwin's Theory of Evolution, and 85 per cent of God-believing people said they believe in evolution as well.
As per Vedas, another explanation for the creation is based on the five elements: earth, water, fire, air and aether.
The Hindu religion traces its beginnings to the Vedas. Everything that is established in the Hindu faith such as the gods and goddesses, doctrines, chants, spiritual insights, etc. flow from the poetry of Vedic hymns. The Vedas offer an honor to the sun and moon, water and wind, and to the order in Nature that is universal. This naturalism is the beginning of what further becomes the connection between Hinduism and science.
=== Islam ===
From an Islamic standpoint, science, the study of nature, is considered to be linked to the concept of Tawhid (the Oneness of God), as are all other branches of knowledge. In Islam, nature is not seen as a separate entity, but rather as an integral part of Islam's holistic outlook on God, humanity, and the world. The Islamic view of science and nature is continuous with that of religion and God. This link implies a sacred aspect to the pursuit of scientific knowledge by Muslims, as nature itself is viewed in the Qur'an as a compilation of signs pointing to the Divine. It was with this understanding that science was studied and understood in Islamic civilizations, specifically during the eighth to sixteenth centuries, prior to the colonization of the Muslim world. Robert Briffault, in The Making of Humanity, asserts that the very existence of science, as it is understood in the modern sense, is rooted in the scientific thought and knowledge that emerged in Islamic civilizations during this time. Ibn al-Haytham, an Arab Muslim, was an early proponent of the concept that a hypothesis must be proved by experiments based on confirmable procedures or mathematical evidence—hence understanding the scientific method 200 years before Renaissance scientists. Ibn al-Haytham described his theology:
I constantly sought knowledge and truth, and it became my belief that for gaining access to the effulgence and closeness to God, there is no better way than that of searching for truth and knowledge.
With the decline of Islamic Civilizations in the late Middle Ages and the rise of Europe, the Islamic scientific tradition shifted into a new period. Institutions that had existed for centuries in the Muslim world looked to the new scientific institutions of European powers. This changed the practice of science in the Muslim world, as Islamic scientists had to confront the western approach to scientific learning, which was based on a different philosophy of nature. From the time of this initial upheaval of the Islamic scientific tradition to the present day, Muslim scientists and scholars have developed a spectrum of viewpoints on the place of scientific learning within the context of Islam, none of which are universally accepted or practiced. However, most maintain the view that the acquisition of knowledge and scientific pursuit in general is not in disaccord with Islamic thought and religious belief.
During the thirteenth century, the Caliphate system in the Islamic Empire fell, and scientific discovery thrived. The Islamic Civilization has a long history of scientific advancement; and their theological practices catalyzed a great deal of scientific discovery. In fact, it was due to necessities of Muslim worship and their vast empire that much science and philosophy was created. People needed to know in which direction they needed to pray toward to face Mecca. Many historians through time have asserted that all modern science originates from ancient Greek scholarship; but scholars like Martin Bernal have claimed that most ancient Greek scholarship relied heavily on the work of scholars from ancient Egypt and the Levant. Ancient Egypt was the foundational site of the Hermetic School, which believed that the sun represented an invisible God. Amongst other things, Islamic civilization was key because it documented and recorded Greek scholarship.
==== Ahmadiyya ====
The Ahmadiyya movement emphasize that "there is no contradiction between Islam and science". For example, Ahmadi Muslims universally accept in principle the process of evolution, albeit divinely guided, and actively promote it. Over the course of several decades the movement has issued various publications in support of the scientific concepts behind the process of evolution, and frequently engages in promoting how religious scriptures, such as the Qur'an, supports the concept. For general purposes, the second Khalifa of the community, Mirza Basheer-ud-Din Mahmood Ahmad says:
The Holy Quran directs attention towards science, time and again, rather than evoking prejudice against it. The Quran has never advised against studying science, lest the reader should become a non-believer; because it has no such fear or concern. The Holy Quran is not worried that if people will learn the laws of nature its spell will break. The Quran has not prevented people from science, rather it states, "Say, 'Reflect on what is happening in the heavens and the earth.'" (Al Younus)
=== Jainism ===
==== Biology ====
Jainism classifies life into two main divisions those who are static by nature (sthavar) and those who are mobile (trasa).
Jain texts describes life in plant long before Jagdish Chandra Bose proved that plants have life. In the Jain philosophy the plant lives are termed as 'Vanaspatikaya'.
==== Jainism and non-creationism ====
Jain theory of causality holds that a cause and its effect are always identical in nature and an immaterial entity like a creator God cannot be the cause of a material entity like the universe. According to Jain belief, it is not possible to create matter out of nothing.[a] The universe and its constituents– soul, matter, space, time, and natural laws have always existed (a static universe, similar to that proposed by the steady state cosmological model).
== Surveys on scientists and the general public ==
=== Scientists ===
Between 1901 and 2000, 654 Nobel prize laureates belonged to 28 different religions. Most (65%) have identified Christianity in its various forms as their religious preference. Specifically on the science-related prizes, Christians have won a total of 73% of all the Chemistry, 65% in Physics, 62% in Medicine, and 54% in all Economics awards. Jews have won 17% of the prizes in Chemistry, 26% in Medicine, and 23% in Physics. Atheists, Agnostics, and Freethinkers have won 7% of the prizes in Chemistry, 9% in Medicine, and 5% in Physics. Muslims have won 13 prizes (three were in scientific categories).
According to scholar Benjamin Beit-Hallahmi, between 1901–2001, about 57% of laureates in scientific fields were Christians, and 26% were of Jewish descent (including Jewish atheists).
==== Global ====
According to a global study on scientists, a significant portion of scientists around the world have religious identities, beliefs, and practices overall. Furthermore, the majority of scientists do not believe there is inherent conflict in being religious and a scientist and stated that "the conflict perspective on science and religion is an invention of the West" since such a view is not prevalent among most of scientists around the world. Instead of seeing religion and science as 'always in conflict' they rather view it through the lenses of various cultural dimensions to the relations between religion and science.
==== Europe ====
According to a study from 2023 "30–39% of Western-European researchers identify with “some religious affiliation”. "30–37% of scientists identify as non-believers or atheists, and an additional 10–28% as agnostic (with wide geographical differences)".
==== United States ====
In 1916, 1,000 leading American scientists were randomly chosen from American Men of Science and 42% believed God existed, 42% disbelieved, and 17% had doubts/did not know; however, when the study was replicated 80 years later using American Men and Women of Science in 1996, the results were very much the same with 39% believing God exists, 45% disbelieved, and 15% had doubts/did not know. In the same 1996 survey, for scientists in the fields of biology, mathematics, and physics/astronomy, belief in a god that is "in intellectual and affective communication with humankind" was most popular among mathematicians (about 45%) and least popular among physicists (about 22%).
In terms of belief in God among elite scientists, such as "great scientists" in the "American Men of Science" or members of the National Academies of Science; 53% disbelieved, 21% were agnostic, and 28% believed in 1914; 68% disbelieved, 17% were agnostic, and 15% believed in 1933; and 72% disbelieved, 21% were agnostic, and 7% believed in 1998. However Eugenie Scott argued that there are methodological issues in the study, including ambiguity in the questions such using a personal definition of God instead of broader definitions of God. A study with simplified wording to include impersonal or non-interventionist ideas of God concluded that 40% of "prominent scientists" in the US believe in a god.
Others have also observed some methodological issues which impacted the results.
A survey conducted between 2005 and 2007 by Elaine Howard Ecklund of University at Buffalo, The State University of New York of 1,646 natural and social science professors at 21 US research universities found that, in terms of belief in God or a higher power, more than 60% expressed either disbelief or agnosticism and more than 30% expressed belief. More specifically, nearly 34% answered "I do not believe in God" and about 30% answered "I do not know if there is a God and there is no way to find out." In the same study, 28% said they believed in God and 8% believed in a higher power that was not God. Ecklund stated that scientists were often able to consider themselves spiritual without religion or belief in god. Ecklund and Scheitle concluded, from their study, that the individuals from non-religious backgrounds disproportionately had self-selected into scientific professions and that the assumption that becoming a scientist necessarily leads to loss of religion is untenable since the study did not strongly support the idea that scientists had dropped religious identities due to their scientific training. Instead, factors such as upbringing, age, and family size were significant influences on religious identification since those who had religious upbringing were more likely to be religious and those who had a non-religious upbringing were more likely to not be religious. The authors also found little difference in religiosity between social and natural scientists.
In terms of perceptions, most social and natural scientists from 21 American universities did not perceive conflict between science and religion, while 37% did. However, in the study, scientists who had experienced limited exposure to religion tended to perceive conflict. In the same study they found that nearly one in five atheist scientists who are parents (17%) are part of religious congregations and have attended a religious service more than once in the past year. Some of the reasons for doing so are their scientific identity (wishing to expose their children to all sources of knowledge so they can make up their own minds), spousal influence, and desire for community.
A 2009 report by the Pew Research Center found that members of the American Association for the Advancement of Science (AAAS) were "much less religious than the general public," with 51% believing in some form of deity or higher power. Specifically, 33% of those polled believe in God, 18% believe in a universal spirit or higher power, and 41% did not believe in either God or a higher power. 48% say they have a religious affiliation, equal to the number who say they are not affiliated with any religious tradition. 17% were atheists, 11% were agnostics, 20% were nothing in particular, 8% were Jewish, 10% were Catholic, 16% were Protestant, 4% were Evangelical, 10% were other religion. The survey also found younger scientists to be "substantially more likely than their older counterparts to say they believe in God". Among the surveyed fields, chemists were the most likely to say they believe in God.
Elaine Ecklund conducted a study from 2011 to 2014 involving the general US population, including rank and file scientists, in collaboration with the AAAS. The study noted that 76% of the scientists identified with a religious tradition. 85% of evangelical scientists had no doubts about the existence of God, compared to 35% of the whole scientific population. In terms of religion and science, 85% of evangelical scientists saw no conflict (73% collaboration, 12% independence), while 75% of the whole scientific population saw no conflict (40% collaboration, 35% independence).
Religious beliefs of US professors were examined using a nationally representative sample of more than 1,400 professors. They found that in the social sciences: 23% did not believe in God, 16% did not know if God existed, 43% believed God existed, and 16% believed in a higher power. Out of the natural sciences: 20% did not believe in God, 33% did not know if God existed, 44% believed God existed, and 4% believed in a higher power. Overall, out of the whole study: 10% were atheists, 13% were agnostic, 19% believe in a higher power, 4% believe in God some of the time, 17% had doubts but believed in God, 35% believed in God and had no doubts.
In 2005, Farr Curlin, a University of Chicago Instructor in Medicine and a member of the MacLean Center for Clinical Medical Ethics, noted in a study that doctors tend to be science-minded religious people. He helped author a study that "found that 76 percent of doctors believe in God and 59 percent believe in some sort of afterlife." Furthermore, "90 percent of doctors in the United States attend religious services at least occasionally, compared to 81 percent of all adults." He reasoned, "The responsibility to care for those who are suffering and the rewards of helping those in need resonate throughout most religious traditions.". A study from 2017 showed 65% of physicians believe in God.
==== Other or multiple countries ====
According to the Study of Secularism in Society and Culture's report on 1,100 scientists in India: 66% are Hindu, 14% did not report a religion, 10% are atheist/no religion, 3% are Muslim, 3% are Christian, 4% are Buddhist, Sikh or other. 39% have a belief in a god, 6% have belief in a god sometimes, 30% do not believe in a god but believe in a higher power, 13% do not know if there is a god, and 12% do not believe in a god. 49% believe in the efficacy of prayer, 90% strongly agree or somewhat agree with approving degrees in Ayurvedic medicine. Furthermore, the term "secularism" is understood to have diverse and simultaneous meanings among Indian scientists: 93% believe it to be tolerance of religions and philosophies, 83% see it as involving separation of church and state, 53% see it as not identifying with religious traditions, 40% see it as absence of religious beliefs, and 20% see it as atheism. Accordingly, 75% of Indian scientists had a "secular" outlook in terms of being tolerant of other religions.
According to the Religion Among Scientists in International Context (RASIC) study on 1,581 scientists from the United Kingdom and 1,763 scientists from India, along with 200 interviews: 65% of U.K. scientists identified as nonreligious and only 6% of Indian scientists identify as nonreligious, 12% of scientists in the U.K. attend religious services on a regular basis and 32% of scientists in India do. In terms of the Indian scientists, 73% of scientists responded that there are basic truths in many religions, 27% said they believe in God and 38% expressed belief in a higher power of some kind. In terms of perceptions of conflict between science and religion, less than half of both U.K. scientists (38%) and Indian scientists (18%) perceived conflict between religion and science.
According to Elaine Ecklund's research on 1,293 atheist scientists from the US and UK, a majority of atheist scientists came from a nonreligious upbringing and never had a religious affiliation. Also, fewer than half of the atheist scientists who were exposed to religion in their youth said science played a role in them becoming an atheist.
=== General public ===
Global studies which have pooled data on religion and science from 1981 to 2001, have noted that countries with greater faith in science also often have stronger religious beliefs, while less religious countries have more skepticism of the impact of science and technology.
Other research cites the National Science Foundation's finding that America has more favorable public attitudes towards science than Europe, Russia, and Japan despite differences in levels of religiosity in these cultures.
Other cross-national studies have found no correlations supporting the contention that religiosity undermines interest in science topics or activities among the general populations globally.
Cross-cultural studies indicate that people tend to use both natural and supernatural explanations for explaining numerous things about the world such as illness, death, and origins. In other words, they do not think of natural and supernatural explanations as antagonistic or dichotomous, but instead see them as coexisting and complementary. The reconciliation of natural and supernatural explanations is normal and pervasive from a psychological standpoint across cultures.
==== Europe ====
A study conducted on adolescents from Christian schools in Northern Ireland, noted a positive relationship between attitudes towards Christianity and science once attitudes towards scientism and creationism were accounted for.
A study on people from Sweden concludes that though the Swedes are among the most non-religious, paranormal beliefs are prevalent among both the young and adult populations. This is likely due to a loss of confidence in institutions such as the Church and Science.
Concerning specific topics like creationism, it is not an exclusively American phenomenon. A poll on adult Europeans revealed that 40% believed in naturalistic evolution, 21% in theistic evolution, 20% in special creation, and 19% are undecided; with the highest concentrations of young earth creationists in Switzerland (21%), Austria (20%), Germany (18%). Other countries such as Netherlands, Britain, and Australia have experienced growth in such views as well.
==== United States ====
According to a 2015 Pew Research Center Study on the public perceptions on science, people's perceptions on conflict with science have more to do with their perceptions of other people's beliefs than their own personal beliefs. For instance, the majority of people with a religious affiliation (68%) saw no conflict between their own personal religious beliefs and science while the majority of those without a religious affiliation (76%) perceived science and religion to be in conflict. The study noted that people who are not affiliated with any religion, also known as "religiously unaffiliated", often have supernatural beliefs and spiritual practices despite them not being affiliated with any religion and also that "just one-in-six religiously unaffiliated adults (16%) say their own religious beliefs conflict with science." Furthermore, the study observed, "The share of all adults who perceive a conflict between science and their own religious beliefs has declined somewhat in recent years, from 36% in 2009 to 30% in 2014. Among those who are affiliated with a religion, the share of people who say there is a conflict between science and their personal religious beliefs dropped from 41% to 34% during this period."
In a 2024 Pew research center report, only 35% of "nones" (atheist, agnostics, and nothing in particular on religious affiliation); believe that the natural world is all there is, while the majority of nones (63%) believe there are spiritual things beyond the world; and the majority of nones (56%) also believe there are some things that science cannot explain.
The 2013 MIT Survey on Science, Religion and Origins examined the views of religious people in America on origins science topics like evolution, the Big Bang, and perceptions of conflicts between science and religion. It found that a large majority of religious people see no conflict between science and religion and only 11% of religious people belong to religions openly rejecting evolution. The fact that the gap between personal and official beliefs of their religions is so large suggests that part of the problem, might be defused by people learning more about their own religious doctrine and the science it endorses, thereby bridging this belief gap. The study concluded that "mainstream religion and mainstream science are neither attacking one another nor perceiving a conflict." Furthermore, they note that this conciliatory view is shared by most leading science organizations such as the American Association for the Advancement of Science (AAAS).
A study was made in collaboration with the AAAS collecting data on the general public from 2011 to 2014, with the focus on evangelicals and evangelical scientists. Even though evangelicals make up only 26% of the US population, the study found that nearly 70 percent of all evangelical Christians do not view science and religion as being in conflict with each other (48% saw them as complementary and 21% saw them as independent) while 73% of the general US population saw no conflict either.
According to Elaine Ecklund's 2018 study, the majority of religious groups see religion and science in collaboration or independent of each other, while the majority of groups without religion see science and religion in conflict.
Other lines of research on perceptions of science among the American public conclude that most religious groups see no general epistemological conflict with science and they have no differences with nonreligious groups in the propensity of seeking out scientific knowledge, although there may be subtle epistemic or moral conflicts when scientists make counterclaims to religious tenets. Findings from the Pew Center note similar findings and also note that the majority of Americans (80–90%) show strong support for scientific research, agree that science makes society and individual's lives better, and 8 in 10 Americans would be happy if their children were to become scientists. Even strict creationists tend to have very favorable views on science.
According to a 2007 poll by the Pew Forum, "while large majorities of Americans respect science and scientists, they are not always willing to accept scientific findings that squarely contradict their religious beliefs." The Pew Forum states that specific factual disagreements are "not common today", though 40% to 50% of Americans do not accept the evolution of humans and other living things, with the "strongest opposition" coming from evangelical Christians at 65% saying life did not evolve. 51% of the population believes humans and other living things evolved: 26% through natural selection only, 21% somehow guided, 4% do not know. In the U.S., biological evolution is the only concrete example of conflict where a significant portion of the American public denies scientific consensus for religious reasons. In terms of advanced industrialized nations, the United States is the most religious.
A 2009 study from the Pew Research Center on Americans perceptions of science, showed a broad consensus that most Americans, including most religious Americans, hold scientific research and scientists themselves in high regard. The study showed that 84% of Americans say they view science as having a mostly positive impact on society. Among those who attend religious services at least once a week, the number is roughly the same at 80%. Furthermore, 70% of U.S. adults think scientists contribute "a lot" to society.
A 2011 study on a national sample of US college students examined whether these students viewed the science / religion relationship as reflecting primarily conflict, collaboration, or independence. The study concluded that the majority of undergraduates in both the natural and social sciences do not see conflict between science and religion. Another finding in the study was that it is more likely for students to move away from a conflict perspective to an independence or collaboration perspective than towards a conflict view.
In the US, people who had no religious affiliation were no more likely than the religious population to have New Age beliefs and practices.
== See also ==
== References ==
== Sources ==
== Further reading ==
== External links == | Wikipedia/Science_and_Religion |
Perspectives on Science and Christian Faith, subtitled Journal of the American Scientific Affiliation, is the academic publication of the American Scientific Affiliation.
== Background ==
The ASA's original constitution provided two goals for the ASA: "(1) to promote and encourage the study of the relationship between the facts of science and Holy Scriptures and (2) to promote the dissemination of the results of such studies." The establishment of the journal was seen as being in context of these goals. The journal is indexed in the ATLA Religion Serials Database.
Perspectives on Science and Christian Faith (PSCF) began publication in 1949 as the Journal of the American Scientific Affiliation (JASA). In its first year the journal was subtitled The American Scientific Affiliation Bulletin. In its first issue it announced its purpose as being:
It is intended primarily for the benefit of the A.S.A. members, and interested friends, and it is hoped that it will be instrumental in helping the organization achieve its primary purpose of witnessing to the truth of the Scriptures and elucidating the relationship of both the ideology and fruits of science thereto. Furthermore we confidently expect that in the publication of papers presented at the convention and others received from the membership at large, a real service will be rendered each of us in creating an enlarged appreciation and understanding of the Christian position in other fields of science than that of our own specialization. Also thru the A.S.A. Bulletin, we plan to give every interested member the benefit of a constructive criticism and Christian evaluation of papers presented and of reviews of books of great interest or strategic importance.
From its beginning the journal included divergent views, and the editorial objectives of the journal, published in December 1950, were a clear indication of the ASA's non-doctrinal focus.
== Editors ==
The editors of the JASA/PSCF have been as follows:
Marion Barnes (1949–1951), research chemist, Lion Oil Company
Delbert N. Eggenberger (1951–1962), research physicist, Argonne National Laboratory
David O. Moberg (1962–1964), Professor of Sociology, Bethel College, Minnesota
Russell L. Mixter (1965–1968), Professor of Biology, Wheaton College, Illinois
Richard H. Bube (1969–1983), Professor of Material Science, Stanford University
Wilbur Bullock (1984–1989), Professor of Biology, University of New Hampshire
John W. Haas, Jr. (1990–1999), Professor of Chemistry, Gordon College, Massachusetts
Roman Miller (2000–2007), Professor of Biology, Eastern Mennonite University
Ari Leegwater (2008–2011), Professor of Chemistry, Calvin College
James C. Peterson (2012–), Charles and Helen Schumann Chair of Christian Ethics, Roanoke College and Roy A. Hope Professor of Theology and Ethics at McMaster Divinity College, McMaster University
== Debates on the creation–evolution controversy ==
The ASA journal published various views in the creation–evolution controversy. It carried Bernard Ramm's view that the theory of evolution had logical weakness, a 1949 article on "presuppositions in evolutionary thinking" by Young Earth creationist E. Y. Monsma, J. Laurence Kulp's 1950 indictment of "Deluge Geology", and Henry M. Morris's anonymous reply to it.
Kulp's paper, Deluge Geology execrated flood geology, which he stated had "grown and infiltrated the greater portion of fundamental Christianity in America primarily due to the absence of trained Christian geologists." He asserted that the "major propositions of the theory are contraindicated by established physical and geological laws" and focused on "four basic errors":
The "confusion that geology and evolution are synonomous [sic]"
Assuming "that life has been on the earth only for a few thousand years, [and] therefore the flood must account for geological strata"
Misunderstanding "the physical and chemical conditions under which rocks are formed"
Ignoring recent discoveries, such as radiometric dating, that undermined their assumptions
Kulp's conclusion was that a Christian was faced with two choices. Either: (1) the earth was created millions of years ago; or (2) God has apparently deceived humanity in providing data which does not support a 6,000- to 10,000-year-old Earth. He viewed "flood geology" as offering no third choice, that it was unscientific, ludicrous, and "has done and will do considerable harm to the strong propagation of the gospel among educated people". He also accused George McCready Price of ignorance and deception, including misrepresentation of geological data when defending flood geology. The paper failed to evoke the fireworks that Kulp and ASA president F. Alton Everest expected it to generate. In the opinion of at least one of the attendees at the annual convention where Monsma's and Kulp's papers were first presented, Monsma had lost the debate to Kulp, and Kulp was appointed that year to the executive council seat that Monsma had vacated. Kulp's influence was largely responsible for isolating flood geologists within the ASA, and Deluge Geology caused them considerable discomfort for years to come.
During the editorship of David O. Moberg (1962–1964), the ASA journal had a heavy emphasis on the creation–evolution controversy, with the subject being mentioned in the majority of issues, and the September 1963 issue being almost entirely devoted to it.
In 1964, JASA featured a pair of hostile reviews of John C. Whitcomb's and Henry M. Morris's The Genesis Flood (introduced by book-review editor Walter R. Hearn, who stated that they had been "edited extensively ... to tone them down a bit"), and in 1969 published a highly critical commentary by J. R. van der Fliert, a Dutch Reformed geologist at the Free University of Amsterdam, who called Whitcomb and Morris "pseudo-scientific" pretenders. "To ensure that no readers missed his point," the journal "ran boldfaced sidebars by evangelical geologists applauding van de Fliert's bare-knuckled approach."
In the 1970s, Richard H. Bube defended the viewpoint of theistic evolution in the journal.
== References ==
== External links ==
Online Archive | Wikipedia/Perspectives_on_Science_and_Christian_Faith |
Muslim scholars have developed a spectrum of viewpoints on science within the context of Islam. Scientists of medieval Muslim civilization (e.g. Ibn al-Haytham) contributed to the new discoveries in science. From the eighth to fifteenth century, Muslim mathematicians and astronomers furthered the development of mathematics. Concerns have been raised about the lack of scientific literacy in parts of the modern Muslim world.
Islamic scientific achievements encompassed a wide range of subject areas, especially medicine, mathematics, astronomy, agriculture as well as physics, economics, engineering and optics.
Aside from these contributions, some Muslim writers have made claims that the Quran made prescient statements about scientific phenomena as regards to the structure of the embryo, the Solar System, and the development of the universe.
== Terminology ==
According to Toby Huff, there is no true word for science in Arabic as commonly defined in English and other languages. In Arabic, "science" can simply mean different forms of knowledge. This view has been criticized by other scholars. For example, according to Muzaffar Iqbal, Huff's framework of inquiry "is based on the synthetic model of Robert Merton who had made no use of any Islamic sources or concepts dealing with the theory of knowledge or social organization" Each branch of science has its own name, but all branches of science have a common prefix, ilm. For example, physics is more literally translated from Arabic as "the science of nature", علم الطبيعة ‘ilm aṭ-ṭabī‘a; arithmetic as the "science of accounts" علم الحساب ilm al-hisab. The religious study of Islam (through Islamic sciences like Quranic exegesis, hadith studies, etc.) is called العلم الديني "science of religion" (al-ilm ad-dinniy), using the same word for science as "the science of nature".
According to the Hans Wehr Dictionary of Arabic, while علم’ ilm is defined as "knowledge, learning, lore," etc. the word for "science" is the plural form علوم’ ulūm. (So, for example, كلية العلوم kullīyat al-‘ulūm, the Faculty of Science of the Egyptian University, is literally "the Faculty of Sciences ...")
== History ==
=== Classical science in the Muslim world ===
One of the earliest accounts of the use of science in the Islamic world is during the eighth and sixteenth centuries, known as the Islamic Golden Age. It is also known as "Arabic science" because of the majority of texts that were translated from Greek into Arabic. The mass translation movement, that occurred in the ninth century allowed for the integration of science into the Islamic world. The teachings from the Greeks were now translated and their scientific knowledge was now passed on to the Arab world. Despite these conditions, not all scientists during this period were Muslim or Arab, as there were a number of notable non-Arab scientists (most notably Persians), as well as some non-Muslim scientists, who contributed to scientific studies in the Muslim world.
A number of modern scholars such as Fielding H. Garrison, Sultan Bashir Mahmood, Hossein Nasr consider modern science and the scientific method to have been greatly inspired by Muslim scientists who introduced a modern empirical, experimental and quantitative approach to scientific inquiry. Certain advances made by medieval Muslim astronomers, geographers and mathematicians were motivated by problems presented in Islamic scripture, such as Al-Khwarizmi's (c. 780–850) development of algebra in order to solve the Islamic inheritance laws, and developments in astronomy, geography, spherical geometry and spherical trigonometry in order to determine the direction of the Qibla, the times of Salah prayers, and the dates of the Islamic calendar. These new studies of math and science would allow for the Islamic world to get ahead of the rest of the world. ‘With these inspiration at work, Muslim mathematicians and astronomers contributed significantly to the development to just about every domain of mathematics between the eight and fifteenth centuries"
The increased use of dissection in Islamic medicine during the 12th and 13th centuries was influenced by the writings of the Islamic theologian, Al-Ghazali, who encouraged the study of anatomy and use of dissections as a method of gaining knowledge of God's creation. In al-Bukhari's and Muslim's collection of sahih hadith it is said: "There is no disease that God has created, except that He also has created its treatment."
(Bukhari 7-71:582). This culminated in the work of Ibn al-Nafis (1213–1288), who discovered the pulmonary circulation in 1242 and used his discovery as evidence for the orthodox Islamic doctrine of bodily resurrection. Ibn al-Nafis also used Islamic scripture as justification for his rejection of wine as self-medication. Criticisms against alchemy and astrology were also motivated by religion, as orthodox Islamic theologians viewed the beliefs of alchemists and astrologists as being superstitious.
Fakhr al-Din al-Razi (1149–1209), in dealing with his conception of physics and the physical world in his Matalib, discusses Islamic cosmology, criticizes the Aristotelian notion of the Earth's centrality within the universe, and "explores the notion of the existence of a multiverse in the context of his commentary," based on the Quranic verse, "All praise belongs to God, Lord of the Worlds." He raises the question of whether the term "worlds" in this verse refers to "multiple worlds within this single universe or cosmos, or to many other universes or a multiverse beyond this known universe." On the basis of this verse, he argues that God has created more than "a thousand thousand worlds (alfa alfi 'awalim) beyond this world such that each one of those worlds be bigger and more massive than this world as well as having the like of what this world has." Ali Kuşçu's (1403–1474) support for the Earth's rotation and his rejection of Aristotelian cosmology (which advocates a stationary Earth) was motivated by religious opposition to Aristotle by orthodox Islamic theologians, such as Al-Ghazali.
According to many historians, science in the Muslim civilization flourished during the Middle Ages, but began declining at some time around the 14th to 16th centuries. At least some scholars blame this on the "rise of a clerical faction which froze this same science and withered its progress." Examples of conflicts with prevailing interpretations of Islam and science – or at least the fruits of science – thereafter include the demolition of Taqi al-Din's great Constantinople observatory in Galata, "comparable in its technical equipment and its specialist personnel with that of his celebrated contemporary, the Danish astronomer Tycho Brahe." But while Brahe's observatory "opened the way to a vast new development of astronomical science," Taqi al-Din's was demolished by a squad of Janissaries, "by order of the sultan, on the recommendation of the Chief Mufti," sometime after 1577 CE.
==== Science and religious practice ====
Scientific methods have been historically applied to find solutions to the technical exigencies of Islamic religious rituals, which is a characteristic of Islam that sets it apart from other religions. These ritual considerations include a lunar calendar, definition of prayer times based on the position of the sun, and a direction of prayer set at a specific location. Scientific methods have also been applied to Islamic laws governing the distribution of inheritances and to Islamic decorative arts. Some of these problems were tackled by both medieval scientists of the Islamic world and scholars of Islamic law. Though these two groups generally used different methods, there is little evidence of serious controversy between them on these subjects, with the exception of the criticism leveled by religious scholars at the methods of astronomy due to its association with astrology.
=== Modern science in the Muslim world ===
At the beginning of the nineteenth century, modern science arrived in the Muslim world, bringing with it "the transfer of various philosophical currents entangled with science" including schools of thought such as Positivism and Darwinism. This had a profound effect on the minds of Muslim scientists and intellectuals and also had a noticeable impact on some Islamic theological doctrines.
While the majority of Muslim scientists tried to adapt their understanding of Islam to the findings of modern science, some rejected modern science as "corrupt foreign thought, considering it incompatible with Islamic teachings", others advocated for the wholesale replacement of religious worldviews with a scientific worldview, and some Muslim philosophers suggested separating the findings of modern science from its philosophical attachments. Among the majority of Muslim thinkers, a key justification for the use of modern science was the benefits that modern knowledge clearly brought to society. Others concluded that science could ultimately be reconciled with faith. A further apologetic trend saw the emergence of theories that scientific discoveries had been predicted in the Quran and Islamic tradition, thereby internalizing science within religion.
According to 2013 survey by the Pew Research Center asking Muslims in different Muslim majority countries in the Middle East and North Africa if there was a conflict between science and religion few agreed in Morocco (18%), Egypt (16%), Iraq (15%), Jordan (15%) and the Palestinian territories (14%). More agreed in Albania (57%), Turkey (40%), Lebanon (53%) and Tunisia (42%).
The poll also found a variance in how Muslim population in some countries are at odds with current scientific theories about biological evolution and the origin of man. Only four of the 22 countries surveyed that at least 50% of the Muslims surveyed rejected evolution (Iraq 67%, Tajikistan 55%, Indonesia 55%, Afghanistan 62%). Countries with relatively low rates of disbelief in evolution (i.e. agreeing to the statement "humans and other living things have always existed in present form") include Lebanon (21%), Albania (24%), Kazakhstan (16%).
As of 2018, three Muslim scientists have won a Nobel Prize for science (Abdus Salam from Pakistan in physics, Ahmed Zewail from Egypt and Aziz Sancar from Turkey in Chemistry). According to Mustafa Akyol, the relative lack of Muslim Nobel laureates in sciences per capita can be attributed to more insular interpretations of the religion than in the golden age of Islamic discovery and development, when Islamic society and intellectuals were more open to foreign ideas. Ahmed Zewail who won the 1999 Nobel Prize in Chemistry and is known as the father of femtochemistry said that "There is nothing fundamental in Islam against science."
However, according to an Islamic scholar from Indonesia, Harun Nasution, said that the stagnation and decline of Islamic civilization in the fields of science and technology was caused by none other than the type of theology that was widely accepted in Islamic society. He blamed Ash'arite theology, which is widely accepted by Muslim society, as the cause of scientific stagnation in the Muslim world. According to him, Ash'arite teachings prioritize occasionalism and fatalism which create a distance between science and Muslim society. On the contrary, he advocated the revival of Mu'tazila thought, known for its rationality, as a potential solution for scientific revival in Muslim society.
==== Conflict with religion ====
The conflicts between Islam and science can become quite complicated. It has been argued that "Muslims must be able to maintain the traditional Islamic intellectual space for the legitimate continuation of the Islamic view of the nature of reality to which Islamic ethics corresponds, without denying the legitimacy of modern science within their own confines". While the natural sciences have not been "fully institutionalized" in predominantly Islamic countries, engineering is considered an applied science that can function in conjunction with religion, and it is one of the most popular career choices of Middle Eastern students. Islamic academic Abu Ammaar Yasir Qadhi has noted that important technological innovations—once "considered to be bizarre, strange, haram (religiously forbidden), bidʻah (innovation), against the tradition" in the Muslim world, were later accepted as "standard".
An issue for accepting scientific knowledge rises from the supposed origin: For Muslims, absolute truth comes from God, not from the flawed human pursuit of knowledge. Islamic values hold that "knowledge of reality [is] based not on reason alone, but also on revelation and inspiration".
A passage in the Quran encourages congruency with the truth attained by modern science: "hence they should be both in agreement and concordant with the findings of modern science". This passage was used more often during the time where "modern science" was full of different discoveries. However, many scientific thinkers through the Islamic word still take this passage to heart when it comes to their work. There are also some strong believers that modern viewpoints, such as social Darwinism, challenged all medieval world views, including that of Islam. Some did not even want to be affiliated with modern science, and thought it was just an outside look into Islam. Many followers tend to see problems regarding the integration of Islam with science, and there are many that still stand by the viewpoints of Ahmad ibn Hanbal, that the pursuit of science is still the pursuit of knowledge:
One of the main reasons the Muslim world was held behind when Europe continued its ascent was that the printing press was banned. And there was a time when the Ottoman Sultan issued a decree that anybody caught with a printing press shall be executed for heresy, and anybody who owns a printed book shall basically be thrown into jail. And for 350 years when Europe is printing, when [René] Descartes is printing, when Galileo is printing, when [Isaac] Newton is printing, the only way you can get a copy of any book in the Arab world is to go and hand write it yourself.
The reluctance of the Muslim world to embrace science is manifest in the disproportionately small amount of scientific output, as measured by citations of articles published in internationally circulating science journals, annual expenditures on research and development, and numbers of research scientists and engineers. Concerns have been raised that the contemporary Muslim world suffers from scientific illiteracy. Skepticism of science among some Muslims is reflected in issues such as the resistance in Muslim northern Nigeria to polio inoculation, which some believe is "an imaginary thing created in the West or it is a ploy to get us to submit to this evil agenda." In Pakistan, a small number of post-graduate physics students have been known to blame earthquakes on "sinfulness, moral laxity, deviation from the Islamic true path", while "only a couple of muffled voices supported the scientific view that earthquakes are a natural phenomenon unaffected by human activity."
In the early twentieth century, Iranian Shia Ulama forbade the learning of foreign languages and the dissection of human bodies in the medical school in Iran. On the other hand, contrary to the current cliché concerning the opposition of the Imamate Shiite Ulama to modern astronomy in the nineteenth century, there is no evidence showing their literal or explicit objection to modern astronomy based on Islamic doctrines. They showed themselves the advocates of modern astronomy with the publication of Hibat al-Dīn Shahristānī's al-Islām wa al-Hayʾa (Islam and Astronomy) in 1910. After that, Shia ulama not only were not against the modern astronomy but also believed that the Quran and Islamic hadiths admit it.
During the twentieth century, the Islamic world introduction to modern science was facilitated by the expansion of educational systems. For example, in 1900 and 1925, Istanbul and Cairo opened universities. In these universities, new concerns have emerged among the students. One major issue was naturalism and social Darwinism, which challenged some beliefs. On the other hand, there were efforts to harmonize science with Islam. An example is the nineteenth-century study of Kudsî of Baku, who made connections between his discoveries in astronomy and what he knew from the Quran. These included "the creation of the universe and the beginning of like; in the second part, with doomsday and the end of the world; and the third was the resurrection after death".
===== Late Ottoman Empire and Turkey =====
Ahmet Hamdi Akseki, supported by the official institute for religious affairs in Turkey (Diyanet), published various articles about the creation of humanity. He emphazises that the purpose of the Quran is to offer parables and moral lessons, not offering scientific data or accounts of history. To demonstrate the ambiguity of the Islamic tradition in regards to the Earth's age he brings forth several narratives embedded in Islamic exegesis.
First, he recounts several narratives about creatures preceding the creation of Adam. Such species include hinn, binn, timm, rimm. A second one adds the belief that, before God has created Adam, thirty previous races were created, each with a gap of thousand years in between. During that time, the earth has been empty, until a new creation began to be formed. Lastly, he offers a dialogue between the Andalusian scholar ibn Arabi and a strange man: During his visit to Mecca, he came across a person in strange cloths. When he asked the identity of the strange man, the man said: "I am from your ancient ancestors. I died forty thousand years ago!" Bewildered by this response, Ibn al-‘Arabı¯ asked, "What are you talking about? Books narrate that Adam was created about six thousand years ago." The man replied "What Adam are you talking about? Beware of the fact that there were a hundred thousand Adams before Adam, your ancestor." The latter, so Akseki, underlines that the idea of Young Earth creationism is a challenge of the Judeo-Christian tradition. He admits that material of a young earth does exists among Muslim commentators, as in the case of ibn Arabi himself, but these are used as supplementary materials borrowed from Jewish sources (Isra'iliyyat) and are not part of the Islamic canon.
Süleyman Ateş, who was president of the Directorate of Religious Affairs in 1976-1978 and issued a tafsir (Interpretation of the Quran), employed similar arguments to that of Aksesi, while using references to Quranic verses to support his arguments. Pointing at 32:7, stating "He began the creation of man from clay.", he points out that humanity was not, in contrast to the Biblical interpretation, created an instant, but emerged as a process. To further support his argument to be in line with Islamic tradition, rather than a secular one, he looked at the Islamic heritage of previous scholars evoking the idea of an evolutionary process, such as the 9th century theologian Jahiz and the 18th century Turkish scholar İbrahim Hakkı Erzurumi, both utilized as references of pre-Darwinian accounts of evolution.
Hasan Karacadağ in his movie Semum, features the trope of conflict between science and religion. When the victim of the movie (Canan) is possessed by a demon, her husband brings her to a psychiatrist (Oğuz) and later to an excorcist (Hoca). A discussion starts between them, those practise is more beneficial to help Canan. While the psychiatrist symbolizes an anti-theistic attitude, Hoca represents a most faithful believer. The psychiatrist calls the Hoca a charlatan and dismisses his belief-system entire, while the Hoca affirms the validity of science, but asserts that science is limited to the knowable world, thus impotent in supernatural matters (i.e. the "unknown"). The Hoca, by his reconciling approach, is depicted as superior, when the demonic cause of Canan's illness is shown. Yet, the film makes clear that the psychiatrist does not fail on behalf of being a scientist, but by his anti-theistism. Exercised properly, science and religion would go hand in hand. When the director was asked if he himself believes in the existence of demons, he said that in such a "chaotic space" it is unlikely that humans are alone. His popular cultural depiction of demons might be seen as a representation of what lies beyond the limits of science, Islam being a tool to guide people to the unknown and unexplainable.
===== Islamist movements =====
Islamist author Muhammad Qutb (brother, and promoter, of Sayyid Qutb) in his influential book Islam, the misunderstood religion, states that "science is a powerful instrument" to increase human knowledge but has become a "corrupting influence on men's thoughts and feelings" for much of the world's population, steering them away from "the Right Path". As an example, he gives the scientific community's disapproval of claims of telepathy, when he claims that it is documented in hadith that Caliph Umar prevented commander Sariah from being ambushed by communicating with him telepathically. Muslim scientists and scholars have subsequently developed a spectrum of viewpoints on the place of scientific learning within the context of Islam.
Until the 1960s, Saudi Sunni ulama opposed any attempts at modernisation, considering them as innovations (bidah). They opposed the spread of electricity, radios, and TVs. As recently as 2015, Sheikh Bandar al-Khaibari rejected the fact that the Earth orbits the Sun, instead claiming that the Earth is "stationary and does not move". In Afghanistan, Sunni Taliban have turned secular schools into Islamic madrasas, prioritizing religious studies over material science.
== Science and the Quran ==
Many Muslims agree that doing science is an act of religious merit, even a collective duty of the Muslim community.
According to M. Shamsher Ali, there are around 750 verses in the Quran dealing with natural phenomena. According to the Encyclopedia of the Quran, many verses of the Quran ask mankind to study nature, and this has been interpreted to mean an encouragement for scientific inquiry, and the investigation of the truth. Some include, "Travel throughout the earth and see how He brings life into being" (Q29:20), "Behold in the creation of the heavens and the earth, and the alternation of night and day, there are indeed signs for men of understanding ..." (Q3:190)
Mohammad Hashim Kamali has stated that "scientific observation, experimental knowledge and rationality" are the primary tools with which humanity can achieve the goals laid out for it in the Quran. Ziauddin Sardar argues that Muslims developed the foundations of modern science, by "highlighting the repeated calls of the Quran to observe and reflect upon natural phenomenon".
The physicist Abdus Salam believed there is no contradiction between Islam and the discoveries that science allows humanity to make about nature and the universe; and that the Quran and the Islamic spirit of study and rational reflection was the source of extraordinary civilizational development. Salam highlights, in particular, the work of Ibn al-Haytham and Al-Biruni as the pioneers of empiricism who introduced the experimental approach, breaking way from Aristotle's influence, and thus giving birth to modern science. Salam differentiated between metaphysics and physics, and advised against empirically probing certain matters on which "physics is silent and will remain so," such as the doctrine of "creation from nothing" which in Salam's view is outside the limits of science and thus "gives way" to religious considerations.
Islam has its own world view system including beliefs about "ultimate reality, epistemology, ontology, ethics, purpose, etc." according to Mehdi Golshani.
Toshihiko Izutsu writes that in Islam, nature is not seen as something separate but as an integral part of a holistic outlook on God, humanity, the world and the cosmos. These links imply a sacred aspect to Muslims' pursuit of scientific knowledge, as nature itself is viewed in the Quran as a compilation of signs pointing to the Divine. It was with this understanding that the pursuit of science, especially prior to the colonization of the Muslim world, was respected in Islamic civilizations.
The astrophysicist Nidhal Guessoum argues that the Quran has developed "the concept of knowledge" that encourages scientific discovery. He writes:
The Qur'an draws attention to the danger of conjecturing without evidence (And follow not that of which you have not the (certain) knowledge of... 17:36) and in several different verses asks Muslims to require proofs (Say: Bring your proof if you are truthful 2:111), both in matters of theological belief and in natural science.
Guessoum cites Ghaleb Hasan on the definition of "proof" according the Quran being "clear and strong... convincing evidence or argument." Also, such a proof cannot rely on an argument from authority, citing verse 5:104. Lastly, both assertions and rejections require a proof, according to verse 4:174. Ismail al-Faruqi and Taha Jabir Alalwani are of the view that any reawakening of the Muslim civilization must start with the Quran; however, the biggest obstacle on this route is the "centuries old heritage of tafseer (exegesis) and other classical disciplines" which inhibit a "universal, epistemiological and systematic conception" of the Quran's message. The philosopher Muhammad Iqbal considered the Quran's methodology and epistemology to be empirical and rational.
Guessoum also suggests scientific knowledge may influence Quranic readings, stating that "for a long time Muslims believed, on the basis on their literal understanding of some Qur’anic verses, that the gender of an unborn baby is only known to God, and the place and time of death of each one of us is likewise al-Ghaib [unknown/unseen]. Such literal under-standings, when confronted with modern scientific (medical) knowledge, led many Muslims to realize that first-degree readings of the Quran can lead to contradictions and predicaments."
Islamists such as Sayyid Qutb argue that since "Islam appointed" Muslims "as representatives of God and made them responsible for learning all the sciences," science cannot but prosper in a society of true Islam. (However, since Muslim majority countries governments have failed to follow the sharia law in its completeness, true Islam has not prevailed and this explains the failure of science and many other things in the Muslim world, according to Qutb.)
Others claim traditional interpretations of Islam are not compatible with the development of science. Author Rodney Stark argues that Islam's lag behind the West in scientific advancement after (roughly) 1500 CE was due to opposition by traditional ulema to efforts to formulate systematic explanation of natural phenomenon with "natural laws." He claims that they believed such laws were blasphemous because they limit "God's freedom to act" as He wishes, a principle enshired in aya 14:4: "God sendeth whom He will astray, and guideth whom He will," which (they believed) applied to all of creation not just humanity.
Taner Edis wrote An Illusion of Harmony: Science and Religion in Islam. Edis worries that secularism in Turkey, one of the most westernized Muslim nations, is on its way out; he points out that the population of Turkey rejects evolution by a large majority. To Edis, many Muslims appreciate technology and respect the role that science plays in its creation. As a result, he says there is a great deal of Islamic pseudoscience attempting to reconcile this respect with other respected religious beliefs. Edis maintains that the motivation to read modern scientific truths into holy books is also stronger for Muslims than Christians. This is because, according to Edis, true criticism of the Quran is almost non-existent in the Muslim world. While Christianity is less prone to see its Holy Book as the direct word of God, fewer Muslims will compromise on this idea – causing them to believe that scientific truths simply must appear in the Quran. However, Edis argues that there are endless examples of scientific discoveries that could be read into the Bible or Quran if one would like to. Edis qualifies that Muslim thought certainly cannot be understood by looking at the Quran alone; cultural and political factors play large roles.
=== Miracle literature (Tafsir'ilmi) ===
Starting in the 1970s and 1980s, the idea of the presence of scientific evidence in the Quran became popularized as ijaz (miracle) literature. The genre of interpreting the Quran as revealing scientific truths before mankind's discovery is also known as Tafsir'ilmi. This approach gained much popularity through French author Maurice Bucaille, whose works have been distributed through Muslim bookstores and websites, and discussed on television programs by Islamic preachers. The movement contends that the Quran abounds with "scientific facts" that appeared centuries before their discovery by science and which "could not have been known" by people at the time. By asserting the presence of scientific truths stemming from the Quran, it also overlaps with Islamic creationism. This approach has been rejected by orthodox theologians who argue that the purpose of the Quran is religious guidance and not for proposing scientific theories.
According to author Ziauddin Sardar, the ijaz movement has created a "global craze in Muslim societies", and has developed into an industry that is "widespread and well-funded". Individuals connected with the movement include Abdul Majeed al-Zindani, who established the Commission on Scientific Signs in the Quran and Sunnah; Zakir Naik, the Indian televangelist; and Adnan Oktar, the Turkish creationist.
Enthusiasts of the movement argue that among the [scientific] miracles found in the Quran are "everything, from relativity, quantum mechanics, Big Bang theory, black holes and pulsars, genetics, embryology, modern geology, thermodynamics, even the laser and hydrogen fuel cells".
Zafar Ishaq Ansari terms the modern trend of claiming the identification of "scientific truths" in the Quran as the "scientific exegesis" of the holy book.
An example is the verse: "So verily I swear by the stars that run and hide ..." (Q81:15–16), which proponents claim demonstrates the Quran's knowledge of the existence of black holes; or: "[I swear by] the Moon in her fullness that ye shall journey on from stage to stage" (Q84:18–19) refers, according to proponents, to human flight into outer space.
==== Embryology in the Quran ====
One claim that has received widespread attention and has even been the subject of a medical school textbook widely used in the Muslim world is that several Quranic verses foretell the study of embryology and "provide a detailed description of the significant events in human development from the stages of gametes and conception until the full term pregnancy and delivery or even post partum."
In 1983, an authority on embryology, Keith L. Moore, had a special edition published of his widely used textbook on embryology (The Developing Human: Clinically Oriented Embryology), co-authored by a leader of the scientific miracles movement, Abdul Majeed al-Zindani. This edition, The Developing Human: Clinically Oriented Embryology with Islamic Additions, interspersed pages of "embryology-related Quranic verse and hadith" by al-Zindani into Moore's original work.
At least one Muslim-born physician (Ali A. Rizvi) studying the textbook of Moore and al-Zindani found himself "confused" by "why Moore was so 'astonished by'" the Quranic references, which Rizvi found "vague", and insofar as they were specific, preceded by the observations of Aristotle and the Ayr-veda, and/or easily explained by "common sense".
Some of the main verses are
(Q39:6) God creates us "in the womb of your mothers, creation after creation, within three darknessess," or "three veils of darkness". The "three" allegedly referring to the abdominal wall, the wall of the uterus, and the chorioamniotic membrane.
Verse Q32:9 identifies the order of organ development of the embryo—ears, then eyes, then heart.
Verses referring to "sperm drop" (an-nutfa), and to al-3alaqa (translated as "clinging clot" or "leech like structure") in (Q23:13-14); and to "sperm-drop mixture" (an-nuṭfatin amshaajin) in (Q76:2). The miraculousness of these verse is said to come from the resemblance of the human embryo to a leech, and to the claim that "sperm-drop mixture" refers to a mixture sperm and egg.
(Q53:45-46) "And that He creates the two mates—the male and female—from a sperm-drop when it is emitted," allegedly refers to the fact that the sperm contributes X and Y chromosomes that determine the gender of the baby.
However,
The "three darknesses" or three walls (Q39:6) could easily have been observed by cutting open of pregnant mammals, something done by human beings before the revelation of the Quran ("dissections of human cadavers by Greek scientists have been documented as early as the third century BCE").
Contrary to the claims made about Q32:9, ears do not develop before eyes, which do not develop before heart. The heart begins development "at about 20 days, and the ears and eyes begin to develop simultaneously in the fourth week". However, the verse itself does not mention or claim the order of how the embryo will form first in the womb. "Then He proportioned him and breathed into him from His [created] soul and made for you hearing and vision and hearts; little are you grateful."
The embryo may resemble a leech (ala "clinging clot" or "leech like structure" of al-3alaqa in Q23:13-14), but it resembles many things during the eight week course of its development—none for very long.
While it is generally agreed the Quran mentions sperm (an-nutfa in several verses), "sperm-drop mixture" (an-nuṭfatin amshaajin in Q76:2) of a mixture of sperm and egg is more problematic as nowhere does the Quran mention the Egg cell or ovum—a rather glaring omission in any description of embryo development, as it the ovum the source of more than half the genetic material of the embryo.
With mention of male sperm but not female egg in the Quran, it seems likely Q53:45-46—"And that He creates the two mates, the male and female, from a sperm-drop when it is emitted"—is talking about the erroneous idea that all genetic material for offspring comes from the male and the mother simply provides a womb for the developing baby (as opposed to the sperm contributing the X and Y chromosomes that determine the gender of the baby). This idea originated with the ancient Greeks and was popular before modern biology developed.
In 2002, Moore declined to be interviewed by The Wall Street Journal on the subject of his work on Islam, stating that "it's been ten or eleven years since I was involved in the Qur'an."
Some researchers have proposed an evolutionary reading of the verses related to the creation of man in the Qur'an and then considered these meanings as examples of scientific miracles.
==== Criticism ====
Critics argue, verses that proponents say explain modern scientific facts, about subjects such as biology, the origin and history of the Earth, and the evolution of human life, contain fallacies and are unscientific.
As of 2008, both Muslims and non-Muslims have disputed whether there actually are "scientific miracles" in the Quran. Muslim critics of the movement include Indian Islamic theologian Maulana Ashraf Ali Thanwi, Muslim historian Syed Nomanul Haq, Muzaffar Iqbal, president of Center for Islam and Science in Alberta, Canada, and Egyptian Muslim scholar Khaled Montaser.
Pakistani theoretical physicist Pervez Hoodbhoy criticizes these claims and says there is no explanation that why many modern scientific discoveries such as quantum mechanics, molecular genetics, etc. were discovered elsewhere.
Giving the example of the roundness of the earth and the invention of the television,
a Christian site ("Evidence for God's Unchanging World") complains the "scientific facts" are too vague to be miraculous.
Critics argue that while it is generally agreed the Quran contains many verses proclaiming the wonders of nature,
it requires "considerable mental gymnastics and distortions to find scientific facts or theories in these verses" (Ziauddin Sardar);
that the Quran is the source of guidance in right faith (iman) and righteous action (alladhina amanu wa amilu l-salihat) but the idea that it contained "all knowledge, including scientific" knowledge has not been a mainstream view among Muslim scholarship (Zafar Ishaq Ansari); and that "Science is ever-changing ... the Copernican revolution overturning polemic models of the universe to Einstein's general relativity overshadowing Newtonian mechanisms". So while "Science is probabilistic in nature" the Quran deals in "absolute certainty". (Ali Talib);
Nidhal Guessoum says that the central issue in the Islam-science discourse is the hierarchical positioning or place of the Quran in the scientific enterprise.
Mustansir Mir argues for a proper approach to Quran with regard to science that allows multiple and multi-level interpretations. He writes:
From a linguistic standpoint, it is quite possible for a word, phrase or statement to have more than one layer of meaning, such that one layer would make sense to one audience in one age and another layer of meaning would, without negating the first, be meaningful to another audience in a subsequent age.
== See also ==
== References ==
=== Notes ===
=== Citations ===
== Further reading ==
Huff, Toby. The Rise of Early Modern Science: Islam, China, and the West (Cambridge University Press, 1993).
Nasr, Seyyed Hossein. "Islam, Muslims, and modern technology." Islam and Science 3.2 (2005): 109–126. online
Stearns, Justin. "The Legal Status of Science in the Muslim World in the Early Modern Period: An Initial Consideration of Fatwās from Three Maghribī Sources." in The Islamic Scholarly Tradition (Brill, 2011) pp. 265–290. online
== External links ==
Islam & Science
Science and the Islamic world—The quest for rapprochement by Pervez Hoodbhoy.
Islamic Science by Ziauddin Sardar (2002).
Can Science Dispense With Religion? Archived 2016-05-29 at the Wayback Machine by Mehdi Golshani.
Islam, science and Muslims by Seyyed Hossein Nasr.
Center for Islam and Science
Explore Islamic achievements and contributions to science
Is There Such A Thing As Islamic Science? The Influence Of Islam On The World Of Science
How Islam Won, and Lost, the Lead in Science
Radicalism among Muslim professionals worries many | Wikipedia/Islam_and_science |
Inner nuclear membrane proteins (INM proteins) are membrane proteins that are embedded in or associated with the inner membrane of the nuclear envelope. There are about 60 INM proteins, most of which are poorly characterized with respect to structure and function. Among the few well-characterized INM proteins are lamin B receptor (LBR), lamina-associated polypeptide 1 (LAP1), lamina-associated polypeptide-2 (LAP2), emerin and MAN1.
== Common structural features ==
Several integral nuclear membrane proteins of different size and structure have been identified. It is proposed that they share some structural features with respect to nucleoplasmic domain(s) and lipid-soluble domain(s). Some INM proteins contain common protein domain structures, and can thus be categorised into known protein domain families. These include the LEM-, SUN-, and KASH-domain families. Members of the LEM-domain family play a part in chromatin organisation . SUN- and KASH-domains participate in linking the cytoskeleton and nucleoskeleton through the LINC complex.
== Function ==
Lamins and chromatin found at the nuclear envelope are organised with the assistance of proteins embedded in the INM. INM proteins also aid in organization of nuclear pore complexes (NPCs). The protein mPom121 is targeted to the INM and is necessary for NPC formation. Proteins containing the LEM domain, such as emerin, LAP2β and MAN1, seem to have a number of roles. They interact with the barrier-to-autointegration factor (BAF). and help to repress gene expression, both by tethering specific genomic regions to the nuclear periphery, and by interaction with histone deacetylase (HDAC) 3.
== Synthesis and translocation ==
There are several proteins associated with the inner nuclear membrane. It is likely that the majority of them are also associated with the nuclear lamina. Some may interact directly with the nuclear lamina, and some may be associated with it through scaffold proteins. All INM proteins are arranged such that their N-termini is facing the nucleoplasm and targeted by various kinases. They are synthesized in one of three places; in the cytoplasm, the cytoplasmic ER, or the outer nuclear membrane. All require localisation to the INM. Since the outer nuclear membrane is continuous with the endoplasmic reticulum it is possible that the inner nuclear membrane proteins are translated on the rough endoplasmic reticulum, whereby the proteins move into the nucleus by lateral diffusion through a nuclear pore. In this model, proteins diffuse freely from the ER to the inner nuclear membrane, where association with nuclear lamina or chromatin immobilizes them. A nuclear localisation signal is not sufficient to target a protein to the INM, and the N-terminal domain of LBR cannot translocate into the nuclear lumen if its size is increased from 22 to approximately 70 kDa, supporting this view. Current opinion is that INM proteins synthesised in the cytoplasm are transported to the INM through nuclear pore complexes (NPC).
== Potential role in cell differentiation ==
It has been proposed that chromatin-binding/modifying proteins embedded within the inner nuclear membrane may be central in determining the identity of newly differentiated cells. The nucleoplasmic domains of such proteins can interact with chromatin to create a scaffold and restrict the conformation of chromosomes within three dimensions. Such inner-nuclear-membrane proteins (INMs) may function simply by restricting the movement of bound chromatin, by recruiting chromatin-remodeling proteins, or through inherent enzyme activity. INM:chromatin interactions causes some segments of chromatin to be more exposed to the nucleoplasm than others.
Once INM:chromatin interactions have been established following formation of the nuclear envelope, soluble nuclear proteins may bind to exposed chromosomal segments. Such proteins could include enzymes that modify histones—such as methylases and acetylases—which act to alter the three-dimensional conformation of chromatin, as well as DNA binding proteins—such as helicases, gyrases, and transcription factors—that are involved in unwinding/looping DNA and/or recruiting RNAP holoenzyme. This will promote the transcription of some genes and down-regulate or prevent transcription of others. Thus, the nuclear scaffold places limits on what genes can and can not be expressed within a given cell and, hence, may serve a basis for cell identity.
Once all regulatory proteins, etc. have been synthesized and the scaffold has been established, the cell has attained its own specific expression profile. This allows it to synthesize cell-specific enzymes and receptors characteristic of its particular function. The nuclear scaffold is predicted to be relatively permanent for a given cell type, but induction of a signaling pathway—by ligand binding, cell:cell contact, or some other mechanism—can temporarily shift the expression profile. When such a signal changes expression of genes coding for INM or a chromatin-modifying enzymes, it can induce differentiation in to a different cell type. Thus, the Nuclear Scaffold Theory predicts that symmetric cell division occurs when a daughter cell contains the same complement of INMs as the parent cell. Conversely, asymmetric cell division is expected to result in parent and daughter cells with different INM profiles.
The INM profile of closely related cells (e.g., CD4+ TH1 and TH2 helper T-cells) is expected to be more similar than for cells that are more distantly related (e.g., T-cells and B-cells). The degree of INM complementarity is expected to be roughly proportional to the degree of relatedness (e.g., % complementarity to TH1 helper T-cells will be: TH2 > CD8+ > B-cell > Erythrocyte > cardiomyocyte). Some cells that are very closely related may have similar INMs, but transient changes in expression—e.g., in response to extracellular signals—could possibly lead to more permanent changes in expression profile by altering transcription rates for chromatin modifying enzymes, transcriptional modulators, or other regulatory proteins.
== Examples ==
Emerin
Lamina-associated polypeptides 1 and 2 (LAP1, LAP2)
Lamin B receptor (LBR)
MAN1
Nurim
Dpy19L1 to L4
== Posttranslational modifications ==
Posttranslational modifications of INM proteins play a critical role in their functional modulation. For example, lamin B receptor, lamina-associated polypeptide 1 and lamina-associated polypeptide 2 are targets for different protein kinases. Arginine and serine residues phosphorylation control LBR's interaction with other subunits of the LBR complex and was proposed to modulate the interaction with chromatin.
== Disease ==
=== Laminopathies ===
The wide array of diseases involving lamins and their associated inner nuclear membrane proteins are collectively called laminopathies. Mutations in the gene EDM, encoding the INM protein emerin may be the cause of X-linked Emery–Dreifuss muscular dystrophy. As mutations in lamins cause the autosomal dominant form of Emery–Dreifuss muscular dystrophy, and lamins and emerin are known to interact, it has been hypothesised that muscle disease is caused by a structural defect in the nuclear envelope brought on by dysfunction in one of these proteins. Mutations in the gene LBR, encoding lamin B receptor, causes Pelger-Hüet anomaly.
=== Cancer ===
Tumor cells often show an aberrant nuclear structure, which is used by pathologists in diagnostics. As changes in the nuclear envelope correspond to functional changes in the nucleus, morphological changes in the nucleus may be involved in carcinogenesis. The regulatory functions of inner nuclear membrane proteins strongly suggest this possibility.
== See also ==
Integral membrane protein
Laminopathy
Transmembrane protein
== References == | Wikipedia/Inner_nuclear_membrane_protein |
The Protein Structure Initiative (PSI) was a USA based project that aimed at accelerating discovery in structural genomics and contribute to understanding biological function. Funded by the U.S. National Institute of General Medical Sciences (NIGMS) between 2000 and 2015, its aim was to reduce the cost and time required to determine three-dimensional protein structures and to develop techniques for solving challenging problems in structural biology, including membrane proteins. Over a dozen research centers have been supported by the PSI for work in building and maintaining high-throughput structural genomics pipelines, developing computational protein structure prediction methods, organizing and disseminating information generated by the PSI, and applying high-throughput structure determination to study a broad range of important biological and biomedical problems.
The project has been organized into three separate phases. The first phase of the Protein Structure Initiative (PSI-1) spanned from 2000 to 2005, and was dedicated to demonstrating the feasibility of high-throughput structure determination, solving unique protein structures, and preparing for a subsequent production phase. The second phase, PSI-2, focused on implementing the high-throughput structure determination methods developed in PSI-1, as well as homology modeling and addressing bottlenecks like modeling membrane proteins. The third phase, PSI:Biology, began in 2010 and consisted of networks of investigators applying high-throughput structure determination to study a broad range of biological and biomedical problems. PSI program ended on 7/1/2015, even that some of the PSI centers continue structure determination supported by other funding mechanisms.
== Phase 1 ==
The first phase of the Protein Structure Initiative (PSI-1) lasted from June 2000 until September 2005, and had a budget of $270 million funded primarily by NIGMS with support from the National Institute of Allergy and Infectious Diseases. PSI-1 saw the establishment of nine pilot centers focusing on structural genomics studies of a range of organisms, including Arabidopsis thaliana, Caenorhabditis elegans and Mycobacterium tuberculosis. During this five-year period over 1,100 protein structures were determined, over 700 of which were classified as "unique" due to their < 30% sequence similarity with other known protein structures.
The primary goal of PSI-1, to develop methods to streamline the structure determination process, resulted in an array of technical advances. Several methods developed during PSI-1 enhanced expression of recombinant proteins in systems like Escherichia coli, Pichia pastoris and insect cell lines. New streamlined approaches to cell cloning, expression and protein purification were also introduced, in which robotics and software platforms were integrated into the protein production pipeline to minimize required manpower, increase speed, and lower costs.
== Phase 2 ==
The second phase of the Protein Structure Initiative (PSI-2) lasted from July 2005 to June 2010. Its goal was to use methods introduced in PSI-1 to determine a large number of proteins and continue development in streamlining the structural genomics pipeline. PSI-2 had a five-year budget of $325 million provided by NIGMS with support from the National Center for Research Resources. By the end of this phase, the Protein Structure Initiative had solved over 4,800 protein structures; over 4,100 of these were unique.
The number of sponsored research centers grew to 14 during PSI-2. Four centers were selected as Large Scale centers, with a mandate to place 15% effort on targets nominated by the broader research community, 15% on targets of biomedical relevance, and 70% on broad structural coverage; these centers were the Joint Center for Structural Genomics (JCSG), the Midwest Center for Structural Genomics (MCSG), the Northeast Structural Genomics Consortium (NESG), and the New York SGX Research Center for Structural Genomics (NYSGXRC). The new centers participating in PSI-2 included four specialized centers: Accelerated Technologies Center for Gene to 3D Structure (ATCG3D), the Center for Eukaryotic Structural Genomics (CESG), the Center for High-Throughput Structural Biology (CHTSB), a branch of the Structural Genomics of Pathogenic Protozoa Consortium taking that institution's place), the Center for Structures of Membrane Proteins (CSMP), and the New York Consortium on Membrane Protein Structure (NYCOMPS). Two homology modeling centers, the Joint Center for Molecular Modeling (JCMM) and New Methods for High-Resolution Comparative Modeling (NMHRCM) were also added, as well as two resource centers, the PSI Materials Repository (PSI-MR) and the PSI Structural Biology Knowledgebase (SBKB). The TB Structural Genomics Consortium was removed from the roster of supported research centers in the transition from PSI-1 to PSI-2.
Originally launched in February 2008, the SBKB is a free resource that provides information on protein sequence and keyword searching, as well as modules describing target selection, experimental protocols, structure models, functional annotation, metrics on overall progress, and updates on structure determination technology. Like the PDB, it is directed by Dr. Helen M. Berman and hosted at Rutgers University.
The PSI Materials Repository, established in 2006 at the Harvard Institute of Proteomics, stores and ships PSI-generated plasmid clones. Clones are sequence-verified, annotated and stored in the DNASU Plasmid Repository, currently located at the Biodesign Institute at Arizona State University. As of September 2011, there are over 50,000 PSI-generated plasmid clones and empty vectors available for request through DNASU in addition to over 147,000 clones generated from non-PSI sources. Plasmids are distributed to researchers worldwide. Now called the PSI:Biology Materials Repository, this resource has a five-year budget of $5.4 million and is under the direction of Dr. Joshua LaBaer, who moved to Arizona State University in the middle of 2009, taking the PSI:Biology-MR with him.
== Phase 3 ==
The third phase of the PSI was called PSI:Biology and was intended to reflect the emphasis on the biological relevance of the work. During this phase, highly organized networks of investigators were applying the new paradigm of high-throughput structure determination, which was successfully developed during the earlier phases of the PSI, to study a broad range of important biological and biomedical problems. The network included centers for high-throughput structure determination, centers for membrane protein structure determination, consortia for high-throughput-enabled structural biology partnerships, the SBKB and the PSI-MR. In September 2013 NIH announced that PSI would not be renewed after its third phase would end in 2015.
== Impact ==
As of January 2006, about two thirds of worldwide structural genomics (SG) output was made by PSI centers. Of these PSI contributions over 20% represented new Pfam families, compared to the non-SG average of 5%. Pfam families represent structurally distinct groups of proteins as predicted from sequenced genomes. Not targeting homologs of known structure was accomplished by using sequence comparison tools like BLAST and PSI-BLAST. Like the difference in novelty as determined by discovery of new Pfam families, the PSI also discovered more SCOP folds and superfamilies than non-SG efforts. In 2006, 16% of structures solved by the PSI represented new SCOP folds and superfamilies, while the non-SG average was 4%. Solving such novel structures reflects increased coverage of protein fold space, one of the PSI's main goals. Determining the structure a novel protein allows homology modeling to more accurately predict the fold of other proteins in the same structural family.
While most of the structures solved by the four large-scale PSI centers lack functional annotation, many of the remaining PSI centers determine structures for proteins with known biological function. The TB Structural Genomics Consortium, for example, focused exclusively on functionally characterized proteins. During its term in PSI-1, it deposited structures for over 70 unique proteins from Mycobacterium tuberculosis, which represented more than 35% of total unique M. tuberculosis structures solved through 2007. In following with its biomedical theme to increase coverage of phosphotomes, the NYSGXRC has determined structures for about 10% of all human phosphatases.
The PSI consortia have provided the overwhelming majority of targets for the Critical Assessment of Techniques for Protein Structure Prediction (CASP), a community-wide, biannual experiment to determine the state and progress of protein structure prediction.
A major goal during the PSI:Biology phase is to utilize the high-throughput methods developed during the initiative's first decade to generate protein structures for functional studies, broadening the PSI's biomedical impact. It is also expected to advance knowledge and understanding of membrane proteins.
== Criticism ==
The PSI has received notable criticism from the structural biology community. Among these charges is that the main product of the PSI – PDB files of proteins' atomic coordinates as determined by X-ray crystallography or NMR spectroscopy – are not useful enough to biologists to justify the project's $764 million cost. Critics note that money currently spent on the PSI could have otherwise funded what they consider worthier causes:
The $60 million a year in public money that is being spent – I would say, wasted – on the PSI is enough to fund approximately 100–200 individual investigator-initiated research grants. These hypothesis-driven proposals are the lifeblood of the scientific enterprise, and as I have discussed recently in other columns, they are being sucked dry by, among other things, an increasing trend to fund large initiatives at their expense. That $60 million a year would raise the payline at a typical NIH institute by about 6 percentile points, enough to make a huge difference to peer review and to the continuance of a lot of important science.
A short response to this was published:
In conclusion, it should be kept in mind that scientific research, and the cutting- edge technologies that both drive and are driven by it, are constantly and rapidly evolving. Some of Petsko’s criticisms are constructive, and should be noted by policy-makers. But one should not throw the baby out with the bathwater, rather tune the scope and objectives of the PSI to the needs of the life-science community as a whole, much in the spirit of SPINE, the SGC and other European structural genomics/ proteomics projects. If such a constructive approach is adopted, we feel confident that the structural data provided by the PSI and its cousins will serve as no less valuable a resource than genome sequences.
In October 2008 the NIGMS hosted a meeting concerning the future of structural genomics efforts and invited speakers from the PSI Advisory Committee, members of the NIGMS Advisory Council, and interested scientists who had no previous involvement with the PSI. Representatives of other genomics, proteomics, and structural genomics initiatives, as well as scientists from academia, government, and industry were also included. Based on this meeting and the subsequent recommendations from the PSI Advisory Committee, a concept-clearance document was released in January 2009 describing what a third phase of the PSI might entail. Most notable was a large emphasis on partnerships and collaborations to ensure that the majority of PSI research is focused on proteins of interest to the broader research community as well as efforts to make PSI products more accessible to the research community.
Grant applications for PSI:Biology were submitted by October 29, 2009. See Phase 3 section above.
== External links ==
Protein Structure Initiative (PSI)
PSI:Biology Funded Centers and Grants
Structural Biology Knowledgebase
PSI:Biology-Materials Repository
Open Protein Structure Annotation Network (TOPSAN), a wiki for annotation of protein structures determined by the PSI
== References == | Wikipedia/Protein_Structure_Initiative |
Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each other and to their surroundings. CAMs are crucial components in maintaining tissue structure and function. In fully developed animals, these molecules play an integral role in generating force and movement and consequently ensuring that organs are able to execute their functions normally. In addition to serving as "molecular glue", CAMs play important roles in the cellular mechanisms of growth, contact inhibition, and apoptosis. Aberrant expression of CAMs may result in a wide range of pathologies, ranging from frostbite to cancer.
== Structure ==
CAMs are typically single-pass transmembrane receptors and are composed of three conserved domains: an intracellular domain that interacts with the cytoskeleton, a transmembrane domain, and an extracellular domain. These proteins can interact in several different ways. The first method is through homophilic binding, where CAMs bind with the same CAMs. They are also capable of heterophilic binding, meaning a CAM on one cell will bind with different CAMs on another cell.
== Families of CAMs ==
There are four major superfamilies or groups of CAMs: the immunoglobulin super family of cell adhesion molecules (IgCAMs), Cadherins, Integrins, and the Superfamily of C-type of lectin-like domains proteins (CTLDs). Proteoglycans are also considered to be a class of CAMs.
One classification system involves the distinction between calcium-independent CAMs and calcium-dependent CAMs. The Ig-superfamily CAMs do not depend on Ca2+ while integrins, cadherins and selectins depend on Ca2+. In addition, integrins participate in cell–matrix interactions, while other CAM families participate in cell–cell interactions.
=== Calcium-independent ===
==== IgSF CAMs ====
Immunoglobulin superfamily CAMs (IgSF CAMs) is regarded as the most diverse superfamily of CAMs. This family is characterized by their extracellular domains containing Ig-like domains. The Ig domains are then followed by Fibronectin type III domain repeats and IgSFs are anchored to the membrane by a GPI moiety. This family is involved in both homophilic or heterophilic binding and has the ability to bind integrins or different IgSF CAMs.
=== Calcium-dependent ===
==== Integrins ====
Integrins, one of the major classes of receptors within the ECM, mediate cell–ECM interactions with collagen, fibrinogen, fibronectin, and vitronectin. Integrins provide essential links between the extracellular environment and the intracellular signalling pathways, which can play roles in cell behaviours such as apoptosis, differentiation, survival, and transcription.
Integrins are heterodimeric, as they consist of an alpha and beta subunit. There are currently 18 alpha subunits and 8 beta subunits, which combine to make up 24 different integrin combinations. Within each of the alpha and beta subunits there is a large extracellular domain, a transmembrane domain and a short cytoplasmic domain. The extracellular domain is where the ligand binds through the use of divalent cations. The integrins contain multiple divalent cation binding sites in the extracellular domain ). The integrin cation binding sites can be occupied by Ca2+ or by Mn2+ ions. Cations are necessary but not sufficient for integrins to convert from the inactive bent conformation into the active extended conformation. Both the presence of cations bound to the multiple cation binding sites is required, along with the direct physical association with ECM ligands for integrins to attain the extended structure and concomitant activation. Thus, rise in extracellular Ca2+ ions may serve to prime the integrin heterodimer. The release of intracellular Ca2+ have been shown to be important for integrin inside-out activation. However, extracellular Ca2+ binding may exert different effects depending on the type of integrin and the cation concentration.
Integrins regulate their activity within the body by changing conformation. Most exist at rest in a low affinity state, which can be altered to high affinity through an external agonist which causes a conformational change within the integrin, increasing their affinity.
An example of this is the aggregation of platelets; Agonists such as thrombin or collagen trigger the integrin into its high affinity state, which causes increased fibrinogen binding, causing platelet aggregation.
==== Cadherins ====
The cadherins are homophilic Ca2+-dependent glycoproteins. The classic cadherins (E-, N- and P-) are concentrated at the intermediate cell junctions, which link to the actin filament network through specific linking proteins called catenins.
Cadherins are notable in embryonic development. For example, cadherins are crucial in gastrulation for the formation of the mesoderm, endoderm, and ectoderm. Cadherins also contribute significantly to the development of the nervous system. The distinct temporal and spatial localization of cadherins implicates these molecules as major players in the process of synaptic stabilization. Each cadherin exhibits a unique pattern of tissue distribution that is carefully controlled by calcium. The diverse family of cadherins include epithelial (E-cadherins), placental (P-cadherins), neural (N-cadherins), retinal (R-cadherins), brain (B-cadherins and T-cadherins), and muscle (M-cadherins). Many cell types express combinations of cadherin types.
The extracellular domain has major repeats called extracellular cadherin domains (ECD). Sequences involved in Ca2+ binding between the ECDs are necessary for cell adhesion. The cytoplasmic domain has specific regions where catenin proteins bind.
==== Selectins ====
The selectins are a family of heterophilic CAMs that are dependent on fucosylated carbohydrates, e.g., mucins for binding. The three family members are E-selectin (endothelial), L-selectin (leukocyte), and P-selectin (platelet). The best-characterized ligand for the three selectins is P-selectin glycoprotein ligand-1 (PSGL-1), which is a mucin-type glycoprotein expressed on all white blood cells. Selectins have been implicated in several roles but they are especially important in the immune system by helping white blood cell homing and trafficking.
== Biological function of CAMs ==
The variety in CAMs leads to diverse functionality of these proteins in the biological setting. One of the CAMS that are particularly important in the lymphocyte homing is addressin. Lymphocyte homing is a key process occurring in a strong immune system. It controls the process of circulating lymphocytes adhering to particular regions and organs of the body. The process is highly regulated by cell adhesion molecules, particularly, the addressin also known as MADCAM1. This antigen is known for its role in tissue-specific adhesion of lymphocytes to high endothelium venules. Through these interactions they play a crucial role in orchestrating circulating lymphocytes.
CAM function in cancer metastasis, inflammation, and thrombosis makes it a viable therapeutic target that is currently being considered. For example, they block the metastatic cancer cells' ability to extravasate and home to secondary sites. This has been successfully demonstrated in metastatic melanoma that hones to the lungs. In mice, when antibodies directed against CAMs in the lung endothelium were used as treatment there was a significant reduction in the number of metastatic sites.
== See also ==
Cell membrane
Cell migration
Immunological synapse
Trogocytosis
== References == | Wikipedia/Cell_adhesion_molecule |
Lipid-anchored proteins (also known as lipid-linked proteins) are proteins that are covalently attached to lipids embedded into biological membranes. The lipid-anchored protein can be located on either side of the cell membrane. Thus, the lipid serves to anchor the protein to the cell membrane. Such proteins are a type of proteolipids.
The lipid groups contribute to the intracellular localization and the biological function of the protein to which they are attached. The lipid serves as a mediator of the protein association with specific biological membranes and protein-protein interactions. The lipidation can also sequester a protein away from its substrate to inactivate the protein and then activate it by substrate presentation.
Overall, there are three main types of lipid-anchored proteins which include prenylated proteins, fatty acylated proteins and glycosylphosphatidylinositol-linked proteins (GPI). A protein can have multiple lipid groups covalently attached to specific amino acid residues.
== Prenylated proteins ==
Prenylated proteins are proteins with covalently attached hydrophobic isoprene polymers (i.e. branched five-carbon hydrocarbon) at cysteine residues of the protein. More specifically, these isoprenoid groups, usually farnesyl (15-carbon) and geranylgeranyl (20-carbon) are attached to the protein via thioether linkages at cysteine residues near the C terminal of the protein. This prenylation of lipid chains to proteins facilitate their interaction with the cell membrane.
The prenylation motif “CaaX box” is the most common prenylation site in proteins, that is, the site where farnesyl or geranylgeranyl covalently attach. In the CaaX box sequence, the C represents the cysteine that is prenylated, the A represents any aliphatic amino acid and the X determines the type of prenylation that will occur. If the X is an Ala, Met, Ser or Gln the protein will be farnesylated via the farnesyltransferase enzyme and if the X is a Leu then the protein will be geranylgeranylated via the geranylgeranyltransferase I enzyme. Both of these enzymes are similar with each containing two subunits.
=== Roles and function ===
Prenylated proteins are particularly important for eukaryotic cell growth, differentiation and morphology. Furthermore, protein prenylation is a reversible post-translational modification to the cell membrane. This dynamic interaction of prenylated proteins with the cell membrane is important for their signalling functions and is often deregulated in disease processes such as cancer. More specifically, Ras is the protein that undergoes prenylation via farnesyltransferase and when it is switched on it can turn on genes involved in cell growth and differentiation. Thus overactiving Ras signalling can lead to cancer. An understanding of these prenylated proteins and their mechanisms have been important for the drug development efforts in combating cancer. Other prenylated proteins include members of the Rab and Rho families as well as lamins.
Some important prenylation chains that are involved in the HMG-CoA reductase metabolic pathway are geranylgeraniol, farnesol and dolichol. These isoprene polymers (e.g. geranyl pyrophosphate and farnesyl pyrophosphate) are involved in the condensations via enzymes such as prenyltransferase that eventually cyclizes to form cholesterol.
== Fatty acylated proteins ==
Fatty acylated proteins are proteins that have been post-translationally modified to include the covalent attachment of fatty acids at certain amino acid residues. The most common fatty acids that are covalently attached to the protein are the saturated myristic (14-carbon) acid and palmitic acid (16-carbon). Proteins can be modified to contain either one or both of these fatty acids.
=== N-myristoylation ===
N-myristoylation (i.e. attachment of myristic acid) is generally an irreversible protein modification that typically occurs during protein synthesis in which the myrisitc acid is attached to the α-amino group of an N-terminal glycine residue through an amide linkage. This reaction is facilitated by N-myristoyltransferase . These proteins usually begin with a Met-Gly sequence and with either a serine or threonine at position 5. Proteins that have been myristoylated are involved in signal transduction cascade, protein-protein interactions and in mechanisms that regulate protein targeting and function. An example in which the myristoylation of a protein is important is in apoptosis, programmed cell death. After the protein BH3 interacting-domain death agonist (Bid) has been myristoylated, it targets the protein to move to the mitochondrial membrane to release cytochrome c, which then ultimately leads to cell death. Other proteins that are myristoylated and involved in the regulation of apoptosis are actin and gelsolin.
=== S-palmitoylation ===
S-palmitoylation (i.e. attachment of palmitic acid) is a reversible protein modification in which a palmitic acid is attached to a specific cysteine residue via thioester linkage. The term S-acylation can also be used when other medium and long fatty acids chains are also attached to palmitoylated proteins. No consensus sequence for protein palmitoylation has been identified. Palmitoylated proteins are mainly found on the cytoplasmic side of the plasma membrane where they play a role in transmembrane signaling. The palmitoyl group can be removed by palmitoyl thioesterases. It is believed that this reverse palmitoylation may regulate the interaction of the protein with the membrane and thus have a role in signaling processes. Furthermore, this allows for the regulation of protein subcellular localization, stability and trafficking. An example in which palmitoylation of a protein plays a role in cell signaling pathways is in the clustering of proteins in the synapse. When the postsynaptic density protein 95 (PSD-95) is palmitoylated, it is restricted to the membrane and allows it to bind to and cluster ion channels in the postsynaptic membrane. Thus, palmitoylation can play a role in the regulation of neurotransmitter release.
Palmitoylation mediates the affinity of a protein for lipid rafts and facilitates the clustering of proteins. The clustering can increase the proximity of two molecules. Alternatively, clustering can sequester a protein away from a substrate. For example, palmitoylation of phospholipase D (PLD) sequesters the enzyme away from its substrate phosphatidylcholine. When cholesterol levels decrease or PIP2 levels increase the palmitate mediated localization is disrupted, the enzyme trafficks to PIP2 where it encounters its substrate and is active by substrate presentation.
== GPI proteins ==
Glycosylphosphatidylinositol-anchored proteins (GPI-anchored proteins) are attached to a GPI complex molecular group via an amide linkage to the protein's C-terminal carboxyl group. This GPI complex consists of several main components that are all interconnected: a phosphoethanolamine, a linear tetrasaccharide (composed of three mannose and a glucosaminyl) and a phosphatidylinositol. The phosphatidylinositol group is glycosidically linked to the non-N-acetylated glucosamine of the tetrasaccharide. A phosphodiester bond is then formed between the mannose at the nonreducing end (of the tetrasaccaride) and the phosphoethanolamine. The phosphoethanolamine is then amide linked to the C-terminal of the carboxyl group of the respective protein. The GPI attachment occurs through the action of GPI-transamidase complex. The fatty acid chains of the phosphatidylinositol are inserted into the membrane and thus are what anchor the protein to the membrane. These proteins are only located on the exterior surface of the plasma membrane.
=== Roles and function ===
The sugar residues in the tetrasaccaride and the fatty acid residues in the phosphatidylinositol group vary depending on the protein. This great diversity is what allows the GPI proteins to have a wide range of functions including acting as hydrolytic enzymes, adhesion molecule, receptors, protease inhibitor and complement regulatory proteins. Furthermore, GPI proteins play an important in embryogenesis, development, neurogenesis, the immune system and fertilization. More specifically, the GPI protein IZUMO1R (also named JUNO after the Roman goddess of fertility) on the egg plasma has an essential role in sperm-egg fusion. Releasing the IZUMO1R (JUNO) GPI protein from the egg plasma membrane does not allow for sperm to fuse with the egg and it is suggested that this mechanism may contribute to the polyspermy block at the plasma membrane in eggs. Other roles that GPI modification allows for is in the association with membrane microdomains, transient homodimerization or in apical sorting in polarized cells.
== References ==
== External links ==
Media related to Lipid-anchored protein at Wikimedia Commons | Wikipedia/Lipid-anchored_protein |
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops (three extracellular loops interacting with ligand molecules, three intracellular loops interacting with G proteins, an N-terminal extracellular region and a C-terminal intracellular region) of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (rhodopsin-like family). They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.
G protein-coupled receptors are found only in eukaryotes, including yeast, and choanoflagellates. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters. They vary in size from small molecules to peptides, to large proteins. G protein-coupled receptors are involved in many diseases.
There are two principal signal transduction pathways involving the G protein-coupled receptors:
the cAMP signal pathway and
the phosphatidylinositol signal pathway.
When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs, Gαi/o, Gαq/11, Gα12/13).: 1160
GPCRs are an important drug target, and approximately 34% of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018. It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of the pharmaceutical research.
== History and significance ==
With the determination of the first structure of the complex between a G-protein coupled receptor (GPCR) and a G-protein trimer (Gαβγ) in 2011 a new chapter of GPCR research was opened for structural investigations of global switches with more than one protein being investigated. The previous breakthroughs involved determination of the crystal structure of the first GPCR, rhodopsin, in 2000 and the crystal structure of the first GPCR with a diffusible ligand (β2AR) in 2007. The way in which the seven transmembrane helices of a GPCR are arranged into a bundle was suspected based on the low-resolution model of frog rhodopsin from cryogenic electron microscopy studies of the two-dimensional crystals. The crystal structure of rhodopsin, that came up three years later, was not a surprise apart from the presence of an additional cytoplasmic helix H8 and a precise location of a loop covering retinal binding site. However, it provided a scaffold which was hoped to be a universal template for homology modeling and drug design for other GPCRs – a notion that proved to be too optimistic.
Results 7 years later were surprising because the crystallization of β2-adrenergic receptor (β2AR) with a diffusible ligand revealed quite a different shape of the receptor extracellular side than that of rhodopsin. This area is important because it is responsible for the ligand binding and is targeted by many drugs. Moreover, the ligand binding site was much more spacious than in the rhodopsin structure and was open to the exterior. In the other receptors crystallized shortly afterwards the binding side was even more easily accessible to the ligand. New structures complemented with biochemical investigations uncovered mechanisms of action of molecular switches which modulate the structure of the receptor leading to activation states for agonists or to complete or partial inactivation states for inverse agonists.
The 2012 Nobel Prize in Chemistry was awarded to Brian Kobilka and Robert Lefkowitz for their work that was "crucial for understanding how G protein-coupled receptors function". There have been at least seven other Nobel Prizes awarded for some aspect of G protein–mediated signaling. As of 2012, two of the top ten global best-selling drugs (Advair Diskus and Abilify) act by targeting G protein-coupled receptors.
== Classification ==
The exact size of the GPCR superfamily is unknown, but at least 831 different human genes (or about 4% of the entire protein-coding genome) have been predicted to code for them from genome sequence analysis. Although numerous classification schemes have been proposed, the superfamily was classically divided into three main classes (A, B, and C) with no detectable shared sequence homology between classes.
The largest class by far is class A, which accounts for nearly 85% of the GPCR genes. Of class A GPCRs, over half of these are predicted to encode olfactory receptors, while the remaining receptors are liganded by known endogenous compounds or are classified as orphan receptors. Despite the lack of sequence homology between classes, all GPCRs have a common structure and mechanism of signal transduction. The very large rhodopsin A group has been further subdivided into 19 subgroups (A1-A19).
According to the classical A-F system, GPCRs can be grouped into six classes based on sequence homology and functional similarity:
Class A (or 1) (Rhodopsin-like)
Class B (or 2) (Secretin receptor family)
Class C (or 3) (Metabotropic glutamate/pheromone)
Class D (or 4) (Fungal mating pheromone receptors)
Class E (or 5) (Cyclic AMP receptors)
Class F (or 6) (Frizzled/Smoothened)
More recently, an alternative classification system called GRAFS (Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, Secretin) has been proposed for vertebrate GPCRs. They correspond to classical classes C, A, B2, F, and B.
An early study based on available DNA sequence suggested that the human genome encodes roughly 750 G protein-coupled receptors, about 350 of which detect hormones, growth factors, and other endogenous ligands. Approximately 150 of the GPCRs found in the human genome have unknown functions.
Some web-servers and bioinformatics prediction methods have been used for predicting the classification of GPCRs according to their amino acid sequence alone, by means of the pseudo amino acid composition approach.
== Physiological roles ==
GPCRs are involved in a wide variety of physiological processes. Some examples of their physiological roles include:
The visual sense: The opsins use a photoisomerization reaction to translate electromagnetic radiation into cellular signals. Rhodopsin, for example, uses the conversion of 11-cis-retinal to all-trans-retinal for this purpose.
The gustatory sense (taste): GPCRs in taste cells mediate release of gustducin in response to bitter-, umami- and sweet-tasting substances.
The sense of smell: Receptors of the olfactory epithelium bind odorants (olfactory receptors) and pheromones (vomeronasal receptors)
Behavioral and mood regulation: Receptors in the mammalian brain bind several different neurotransmitters, including serotonin, dopamine, histamine, GABA, and glutamate
Regulation of immune system activity and inflammation: chemokine receptors bind ligands that mediate intercellular communication between cells of the immune system; receptors such as histamine receptors bind inflammatory mediators and engage target cell types in the inflammatory response. GPCRs are also involved in immune-modulation, e. g. regulating interleukin induction or suppressing TLR-induced immune responses from T cells.
Autonomic nervous system transmission: Both the sympathetic and parasympathetic nervous systems are regulated by GPCR pathways, responsible for control of many automatic functions of the body such as blood pressure, heart rate, and digestive processes
Cell density sensing: A novel GPCR role in regulating cell density sensing.
Homeostasis modulation (e.g., water balance).
Involved in growth and metastasis of some types of tumors.
Used in the endocrine system for peptide and amino-acid derivative hormones that bind to GCPRs on the cell membrane of a target cell. This activates cAMP, which in turn activates several kinases, allowing for a cellular response, such as transcription.
== Receptor structure ==
GPCRs are integral membrane proteins that possess seven membrane-spanning domains or transmembrane helices. The extracellular parts of the receptor can be glycosylated. These extracellular loops also contain two highly conserved cysteine residues that form disulfide bonds to stabilize the receptor structure. Some seven-transmembrane helix proteins (channelrhodopsin) that resemble GPCRs may contain ion channels, within their protein.
In 2000, the first crystal structure of a mammalian GPCR, that of bovine rhodopsin (1F88), was solved. In 2007, the first structure of a human GPCR was solved This human β2-adrenergic receptor GPCR structure proved highly similar to the bovine rhodopsin. The structures of activated or agonist-bound GPCRs have also been determined. These structures indicate how ligand binding at the extracellular side of a receptor leads to conformational changes in the cytoplasmic side of the receptor. The biggest change is an outward movement of the cytoplasmic part of the 5th and 6th transmembrane helix (TM5 and TM6). The structure of activated beta-2 adrenergic receptor in complex with Gs confirmed that the Gα binds to a cavity created by this movement.
GPCRs exhibit a similar structure to some other proteins with seven transmembrane domains, such as microbial rhodopsins and adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2). However, these 7TMH (7-transmembrane helices) receptors and channels do not associate with G proteins. In addition, ADIPOR1 and ADIPOR2 are oriented oppositely to GPCRs in the membrane (i.e. GPCRs usually have an extracellular N-terminus, cytoplasmic C-terminus, whereas ADIPORs are inverted).
== Structure–function relationships ==
In terms of structure, GPCRs are characterized by an extracellular N-terminus, followed by seven transmembrane (7-TM) α-helices (TM-1 to TM-7) connected by three intracellular (IL-1 to IL-3) and three extracellular loops (EL-1 to EL-3), and finally an intracellular C-terminus. The GPCR arranges itself into a tertiary structure resembling a barrel, with the seven transmembrane helices forming a cavity within the plasma membrane that serves a ligand-binding domain that is often covered by EL-2. Ligands may also bind elsewhere, however, as is the case for bulkier ligands (e.g., proteins or large peptides), which instead interact with the extracellular loops, or, as illustrated by the class C metabotropic glutamate receptors (mGluRs), the N-terminal tail. The class C GPCRs are distinguished by their large N-terminal tail, which also contains a ligand-binding domain. Upon glutamate-binding to an mGluR, the N-terminal tail undergoes a conformational change that leads to its interaction with the residues of the extracellular loops and TM domains. The eventual effect of all three types of agonist-induced activation is a change in the relative orientations of the TM helices (likened to a twisting motion) leading to a wider intracellular surface and "revelation" of residues of the intracellular helices and TM domains crucial to signal transduction function (i.e., G-protein coupling). Inverse agonists and antagonists may also bind to a number of different sites, but the eventual effect must be prevention of this TM helix reorientation.
The structure of the N- and C-terminal tails of GPCRs may also serve important functions beyond ligand-binding. For example, The C-terminus of M3 muscarinic receptors is sufficient, and the six-amino-acid polybasic (KKKRRK) domain in the C-terminus is necessary for its preassembly with Gq proteins. In particular, the C-terminus often contains serine (Ser) or threonine (Thr) residues that, when phosphorylated, increase the affinity of the intracellular surface for the binding of scaffolding proteins called β-arrestins (β-arr). Once bound, β-arrestins both sterically prevent G-protein coupling and may recruit other proteins, leading to the creation of signaling complexes involved in extracellular-signal regulated kinase (ERK) pathway activation or receptor endocytosis (internalization). As the phosphorylation of these Ser and Thr residues often occurs as a result of GPCR activation, the β-arr-mediated G-protein-decoupling and internalization of GPCRs are important mechanisms of desensitization. In addition, internalized "mega-complexes" consisting of a single GPCR, β-arr(in the tail conformation), and heterotrimeric G protein exist and may account for protein signaling from endosomes.
A final common structural theme among GPCRs is palmitoylation of one or more sites of the C-terminal tail or the intracellular loops. Palmitoylation is the covalent modification of cysteine (Cys) residues via addition of hydrophobic acyl groups, and has the effect of targeting the receptor to cholesterol- and sphingolipid-rich microdomains of the plasma membrane called lipid rafts. As many of the downstream transducer and effector molecules of GPCRs (including those involved in negative feedback pathways) are also targeted to lipid rafts, this has the effect of facilitating rapid receptor signaling.
GPCRs respond to extracellular signals mediated by a huge diversity of agonists, ranging from proteins to biogenic amines to protons, but all transduce this signal via a mechanism of G-protein coupling. This is made possible by a guanine-nucleotide exchange factor (GEF) domain primarily formed by a combination of IL-2 and IL-3 along with adjacent residues of the associated TM helices.
== Mechanism ==
The G protein-coupled receptor is activated by an external signal in the form of a ligand or other signal mediator. This creates a conformational change in the receptor, causing activation of a G protein. Further effect depends on the type of G protein. G proteins are subsequently inactivated by GTPase activating proteins, known as RGS proteins.
=== Ligand binding ===
GPCRs include one or more receptors for the following ligands:
sensory signal mediators (e.g., light and olfactory stimulatory molecules);
adenosine, bombesin, bradykinin, endothelin, γ-aminobutyric acid (GABA), hepatocyte growth factor (HGF), melanocortins, neuropeptide Y, opioid peptides, opsins, somatostatin, GH, tachykinins, members of the vasoactive intestinal peptide family, and vasopressin;
biogenic amines (e.g., dopamine, epinephrine, norepinephrine, histamine, serotonin, and melatonin);
glutamate (metabotropic effect);
glucagon;
acetylcholine (muscarinic effect);
chemokines;
lipid mediators of inflammation (e.g., prostaglandins, prostanoids, platelet-activating factor, and leukotrienes);
peptide hormones (e.g., calcitonin, C5a anaphylatoxin, follicle-stimulating hormone [FSH], gonadotropin-releasing hormone [GnRH], neurokinin, thyrotropin-releasing hormone [TRH], and oxytocin);
and endocannabinoids.
GPCRs that act as receptors for stimuli that have not yet been identified are known as orphan receptors.
However, in contrast to other types of receptors that have been studied, wherein ligands bind externally to the membrane, the ligands of GPCRs typically bind within the transmembrane domain. However, protease-activated receptors are activated by cleavage of part of their extracellular domain.
=== Conformational change ===
The transduction of the signal through the membrane by the receptor is not completely understood. It is known that in the inactive state, the GPCR is bound to a heterotrimeric G protein complex. Binding of an agonist to the GPCR results in a conformational change in the receptor that is transmitted to the bound Gα subunit of the heterotrimeric G protein via protein domain dynamics. The activated Gα subunit exchanges GTP in place of GDP which in turn triggers the dissociation of Gα subunit from the Gβγ dimer and from the receptor. The dissociated Gα and Gβγ subunits interact with other intracellular proteins to continue the signal transduction cascade while the freed GPCR is able to rebind to another heterotrimeric G protein to form a new complex that is ready to initiate another round of signal transduction.
It is believed that a receptor molecule exists in a conformational equilibrium between active and inactive biophysical states. The binding of ligands to the receptor may shift the equilibrium toward the active receptor states. Three types of ligands exist: Agonists are ligands that shift the equilibrium in favour of active states; inverse agonists are ligands that shift the equilibrium in favour of inactive states; and neutral antagonists are ligands that do not affect the equilibrium. It is not yet known how exactly the active and inactive states differ from each other.
=== G-protein activation/deactivation cycle ===
When the receptor is inactive, the GEF domain may be bound to an also inactive α-subunit of a heterotrimeric G-protein. These "G-proteins" are a trimer of α, β, and γ subunits (known as Gα, Gβ, and Gγ, respectively) that is rendered inactive when reversibly bound to Guanosine diphosphate (GDP) (or, alternatively, no guanine nucleotide) but active when bound to guanosine triphosphate (GTP). Upon receptor activation, the GEF domain, in turn, allosterically activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein's α-subunit. The cell maintains a 10:1 ratio of cytosolic GTP:GDP so exchange for GTP is ensured. At this point, the subunits of the G-protein dissociate from the receptor, as well as each other, to yield a Gα-GTP monomer and a tightly interacting Gβγ dimer, which are now free to modulate the activity of other intracellular proteins. The extent to which they may diffuse, however, is limited due to the palmitoylation of Gα and the presence of an isoprenoid moiety that has been covalently added to the C-termini of Gγ.
Because Gα also has slow GTP→GDP hydrolysis capability, the inactive form of the α-subunit (Gα-GDP) is eventually regenerated, thus allowing reassociation with a Gβγ dimer to form the "resting" G-protein, which can again bind to a GPCR and await activation. The rate of GTP hydrolysis is often accelerated due to the actions of another family of allosteric modulating proteins called regulators of G-protein signaling, or RGS proteins, which are a type of GTPase-activating protein, or GAP. In fact, many of the primary effector proteins (e.g., adenylate cyclases) that become activated/inactivated upon interaction with Gα-GTP also have GAP activity. Thus, even at this early stage in the process, GPCR-initiated signaling has the capacity for self-termination.
=== Crosstalk ===
GPCRs downstream signals have been shown to possibly interact with integrin signals, such as FAK. Integrin signaling will phosphorylate FAK, which can then decrease GPCR Gαs activity.
== Signaling ==
If a receptor in an active state encounters a G protein, it may activate it. Some evidence suggests that receptors and G proteins are actually pre-coupled. For example, binding of G proteins to receptors affects the receptor's affinity for ligands. Activated G proteins are bound to GTP.
Further signal transduction depends on the type of G protein. The enzyme adenylate cyclase is an example of a cellular protein that can be regulated by a G protein, in this case the G protein Gs. Adenylate cyclase activity is activated when it binds to a subunit of the activated G protein. Activation of adenylate cyclase ends when the G protein returns to the GDP-bound state.
Adenylate cyclases (of which 9 membrane-bound and one cytosolic forms are known in humans) may also be activated or inhibited in other ways (e.g., Ca2+/calmodulin binding), which can modify the activity of these enzymes in an additive or synergistic fashion along with the G proteins.
The signaling pathways activated through a GPCR are limited by the primary sequence and tertiary structure of the GPCR itself but ultimately determined by the particular conformation stabilized by a particular ligand, as well as the availability of transducer molecules. Currently, GPCRs are considered to utilize two primary types of transducers: G-proteins and β-arrestins. Because β-arr's have high affinity only to the phosphorylated form of most GPCRs (see above or below), the majority of signaling is ultimately dependent upon G-protein activation. However, the possibility for interaction does allow for G-protein-independent signaling to occur.
=== G-protein-dependent signaling ===
There are three main G-protein-mediated signaling pathways, mediated by four sub-classes of G-proteins distinguished from each other by sequence homology (Gαs, Gαi/o, Gαq/11, and Gα12/13). Each sub-class of G-protein consists of multiple proteins, each the product of multiple genes or splice variations that may imbue them with differences ranging from subtle to distinct with regard to signaling properties, but in general they appear reasonably grouped into four classes. Because the signal transducing properties of the various possible βγ combinations do not appear to radically differ from one another, these classes are defined according to the isoform of their α-subunit.: 1163
While most GPCRs are capable of activating more than one Gα-subtype, they also show a preference for one subtype over another. When the subtype activated depends on the ligand that is bound to the GPCR, this is called functional selectivity (also known as agonist-directed trafficking, or conformation-specific agonism). However, the binding of any single particular agonist may also initiate activation of multiple different G-proteins, as it may be capable of stabilizing more than one conformation of the GPCR's GEF domain, even over the course of a single interaction. In addition, a conformation that preferably activates one isoform of Gα may activate another if the preferred is less available. Furthermore, feedback pathways may result in receptor modifications (e.g., phosphorylation) that alter the G-protein preference. Regardless of these various nuances, the GPCR's preferred coupling partner is usually defined according to the G-protein most obviously activated by the endogenous ligand under most physiological or experimental conditions.
==== Gα signaling ====
The effector of both the Gαs and Gαi/o pathways is the cyclic-adenosine monophosphate (cAMP)-generating enzyme adenylate cyclase, or AC. While there are ten different AC gene products in mammals, each with subtle differences in tissue distribution or function, all catalyze the conversion of cytosolic adenosine triphosphate (ATP) to cAMP, and all are directly stimulated by G-proteins of the Gαs class. In contrast, however, interaction with Gα subunits of the Gαi/o type inhibits AC from generating cAMP. Thus, a GPCR coupled to Gαs counteracts the actions of a GPCR coupled to Gαi/o, and vice versa. The level of cytosolic cAMP may then determine the activity of various ion channels as well as members of the ser/thr-specific protein kinase A (PKA) family. Thus cAMP is considered a second messenger and PKA a secondary effector.
The effector of the Gαq/11 pathway is phospholipase C-β (PLCβ), which catalyzes the cleavage of membrane-bound phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers inositol (1,4,5) trisphosphate (IP3) and diacylglycerol (DAG). IP3 acts on IP3 receptors found in the membrane of the endoplasmic reticulum (ER) to elicit Ca2+ release from the ER, while DAG diffuses along the plasma membrane where it may activate any membrane localized forms of a second ser/thr kinase called protein kinase C (PKC). Since many isoforms of PKC are also activated by increases in intracellular Ca2+, both these pathways can also converge on each other to signal through the same secondary effector. Elevated intracellular Ca2+ also binds and allosterically activates proteins called calmodulins, which in turn tosolic small GTPase, Rho. Once bound to GTP, Rho can then go on to activate various proteins responsible for cytoskeleton regulation such as Rho-kinase (ROCK). Most GPCRs that couple to Gα12/13 also couple to other sub-classes, often Gαq/11.
==== Gβγ signaling ====
The above descriptions ignore the effects of Gβγ–signalling, which can also be important, in particular in the case of activated Gαi/o-coupled GPCRs. The primary effectors of Gβγ are various ion channels, such as G-protein-regulated inwardly rectifying K+ channels (GIRKs), P/Q- and N-type voltage-gated Ca2+ channels, as well as some isoforms of AC and PLC, along with some phosphoinositide-3-kinase (PI3K) isoforms.
=== G-protein-independent signaling ===
Although they are classically thought of working only together, GPCRs may signal through G-protein-independent mechanisms, and heterotrimeric G-proteins may play functional roles independent of GPCRs. GPCRs may signal independently through many proteins already mentioned for their roles in G-protein-dependent signaling such as β-arrs, GRKs, and Srcs. Such signaling has been shown to be physiologically relevant, for example, β-arrestin signaling mediated by the chemokine receptor CXCR3 was necessary for full efficacy chemotaxis of activated T cells. In addition, further scaffolding proteins involved in subcellular localization of GPCRs (e.g., PDZ-domain-containing proteins) may also act as signal transducers. Most often the effector is a member of the MAPK family.
==== Examples ====
In the late 1990s, evidence began accumulating to suggest that some GPCRs are able to signal without G proteins. The ERK2 mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many pathways, has been shown to be activated in response to cAMP-mediated receptor activation in the slime mold D. discoideum despite the absence of the associated G protein α- and β-subunits.
In mammalian cells, the much-studied β2-adrenoceptor has been demonstrated to activate the ERK2 pathway after arrestin-mediated uncoupling of G-protein-mediated signaling. Therefore, it seems likely that some mechanisms previously believed related purely to receptor desensitisation are actually examples of receptors switching their signaling pathway, rather than simply being switched off.
In kidney cells, the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine-phosphorylated ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is necessary to mediate this interaction and subsequently the antiproliferative effect of bradykinin.
==== GPCR-independent signaling by heterotrimeric G-proteins ====
Although it is a relatively immature area of research, it appears that heterotrimeric G-proteins may also take part in non-GPCR signaling. There is evidence for roles as signal transducers in nearly all other types of receptor-mediated signaling, including integrins, receptor tyrosine kinases (RTKs), cytokine receptors (JAK/STATs), as well as modulation of various other "accessory" proteins such as GEFs, guanine-nucleotide dissociation inhibitors (GDIs) and protein phosphatases. There may even be specific proteins of these classes whose primary function is as part of GPCR-independent pathways, termed activators of G-protein signalling (AGS). Both the ubiquity of these interactions and the importance of Gα vs. Gβγ subunits to these processes are still unclear.
== Details of cAMP and PIP2 pathways ==
There are two principal signal transduction pathways involving the G protein-linked receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway.
=== cAMP signal pathway ===
The cAMP signal transduction contains five main characters: stimulative hormone receptor (Rs) or inhibitory hormone receptor (Ri); stimulative regulative G-protein (Gs) or inhibitory regulative G-protein (Gi); adenylyl cyclase; protein kinase A (PKA); and cAMP phosphodiesterase.
Stimulative hormone receptor (Rs) is a receptor that can bind with stimulative signal molecules, while inhibitory hormone receptor (Ri) is a receptor that can bind with inhibitory signal molecules.
Stimulative regulative G-protein is a G-protein linked to stimulative hormone receptor (Rs), and its α subunit upon activation could stimulate the activity of an enzyme or other intracellular metabolism. On the contrary, inhibitory regulative G-protein is linked to an inhibitory hormone receptor, and its α subunit upon activation could inhibit the activity of an enzyme or other intracellular metabolism.
Adenylyl cyclase is a 12-transmembrane glycoprotein that catalyzes the conversion of ATP to cAMP with the help of cofactor Mg2+ or Mn2+. The cAMP produced is a second messenger in cellular metabolism and is an allosteric activator of protein kinase A.
Protein kinase A is an important enzyme in cell metabolism due to its ability to regulate cell metabolism by phosphorylating specific committed enzymes in the metabolic pathway. It can also regulate specific gene expression, cellular secretion, and membrane permeability. The protein enzyme contains two catalytic subunits and two regulatory subunits. When there is no cAMP, the complex is inactive. When cAMP binds to the regulatory subunits, their conformation is altered, causing the dissociation of the regulatory subunits, which activates protein kinase A and allows further biological effects.
These signals then can be terminated by cAMP phosphodiesterase, which is an enzyme that degrades cAMP to 5'-AMP and inactivates protein kinase A.
=== Phosphatidylinositol signal pathway ===
In the phosphatidylinositol signal pathway, the extracellular signal molecule binds with the G-protein receptor (Gq) on the cell surface and activates phospholipase C, which is located on the plasma membrane. The lipase hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 binds with the IP3 receptor in the membrane of the smooth endoplasmic reticulum and mitochondria to open Ca2+ channels. DAG helps activate protein kinase C (PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses.
The effects of Ca2+ are also remarkable: it cooperates with DAG in activating PKC and can activate the CaM kinase pathway, in which calcium-modulated protein calmodulin (CaM) binds Ca2+, undergoes a change in conformation, and activates CaM kinase II, which has unique ability to increase its binding affinity to CaM by autophosphorylation, making CaM unavailable for the activation of other enzymes. The kinase then phosphorylates target enzymes, regulating their activities. The two signal pathways are connected together by Ca2+-CaM, which is also a regulatory subunit of adenylyl cyclase and phosphodiesterase in the cAMP signal pathway.
== Receptor regulation ==
GPCRs become desensitized when exposed to their ligand for a long period of time. There are two recognized forms of desensitization: 1) homologous desensitization, in which the activated GPCR is downregulated; and 2) heterologous desensitization, wherein the activated GPCR causes downregulation of a different GPCR. The key reaction of this downregulation is the phosphorylation of the intracellular (or cytoplasmic) receptor domain by protein kinases.
=== Phosphorylation by cAMP-dependent protein kinases ===
Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was activated by the receptor) via adenylate cyclase and cyclic AMP (cAMP). In a feedback mechanism, these activated kinases phosphorylate the receptor. The longer the receptor remains active the more kinases are activated and the more receptors are phosphorylated. In β2-adrenoceptors, this phosphorylation results in the switching of the coupling from the Gs class of G-protein to the Gi class. cAMP-dependent PKA mediated phosphorylation can cause heterologous desensitisation in receptors other than those activated.
=== Phosphorylation by GRKs ===
The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs. G-protein-coupled receptor kinases (GRKs) are key modulators of G-protein-coupled receptor (GPCR) signaling. They constitute a family of seven mammalian serine-threonine protein kinases that phosphorylate agonist-bound receptor. GRKs-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization. Activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium-sensitive proteins.
Phosphorylation of the receptor can have two consequences:
Translocation: The receptor is, along with the part of the membrane it is embedded in, brought to the inside of the cell, where it is dephosphorylated within the acidic vesicular environment and then brought back. This mechanism is used to regulate long-term exposure, for example, to a hormone, by allowing resensitisation to follow desensitisation. Alternatively, the receptor may undergo lysozomal degradation, or remain internalised, where it is thought to participate in the initiation of signalling events, the nature of which depending on the internalised vesicle's subcellular localisation.
Arrestin linking: The phosphorylated receptor can be linked to arrestin molecules that prevent it from binding (and activating) G proteins, in effect switching it off for a short period of time. This mechanism is used, for example, with rhodopsin in retina cells to compensate for exposure to bright light. In many cases, arrestin's binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β2-adrenoreceptors acts as an adaptor for binding with clathrin, and with the beta-subunit of AP2 (clathrin adaptor molecules); thus, the arrestin here acts as a scaffold assembling the components needed for clathrin-mediated endocytosis of β2-adrenoreceptors.
=== Mechanisms of GPCR signal termination ===
As mentioned above, G-proteins may terminate their own activation due to their intrinsic GTP→GDP hydrolysis capability. However, this reaction proceeds at a slow rate (≈0.02 times/sec) and, thus, it would take around 50 seconds for any single G-protein to deactivate if other factors did not come into play. Indeed, there are around 30 isoforms of RGS proteins that, when bound to Gα through their GAP domain, accelerate the hydrolysis rate to ≈30 times/sec. This 1500-fold increase in rate allows for the cell to respond to external signals with high speed, as well as spatial resolution due to limited amount of second messenger that can be generated and limited distance a G-protein can diffuse in 0.03 seconds. For the most part, the RGS proteins are promiscuous in their ability to deactivate G-proteins, while which RGS is involved in a given signaling pathway seems more determined by the tissue and GPCR involved than anything else. In addition, RGS proteins have the additional function of increasing the rate of GTP-GDP exchange at GPCRs, (i.e., as a sort of co-GEF) further contributing to the time resolution of GPCR signaling.
In addition, the GPCR may be desensitized itself. This can occur as:
a direct result of ligand occupation, wherein the change in conformation allows recruitment of GPCR-Regulating Kinases (GRKs), which go on to phosphorylate various serine/threonine residues of IL-3 and the C-terminal tail. Upon GRK phosphorylation, the GPCR's affinity for β-arrestin (β-arrestin-1/2 in most tissues) is increased, at which point β-arrestin may bind and act to both sterically hinder G-protein coupling as well as initiate the process of receptor internalization through clathrin-mediated endocytosis. Because only the liganded receptor is desensitized by this mechanism, it is called homologous desensitization
the affinity for β-arrestin may be increased in a ligand occupation and GRK-independent manner through phosphorylation of different ser/thr sites (but also of IL-3 and the C-terminal tail) by PKC and PKA. These phosphorylations are often sufficient to impair G-protein coupling on their own as well.
PKC/PKA may, instead, phosphorylate GRKs, which can also lead to GPCR phosphorylation and β-arrestin binding in an occupation-independent manner. These latter two mechanisms allow for desensitization of one GPCR due to the activities of others, or heterologous desensitization. GRKs may also have GAP domains and so may contribute to inactivation through non-kinase mechanisms as well. A combination of these mechanisms may also occur.
Once β-arrestin is bound to a GPCR, it undergoes a conformational change allowing it to serve as a scaffolding protein for an adaptor complex termed AP-2, which in turn recruits another protein called clathrin. If enough receptors in the local area recruit clathrin in this manner, they aggregate and the membrane buds inwardly as a result of interactions between the molecules of clathrin, in a process called opsonization. Once the pit has been pinched off the plasma membrane due to the actions of two other proteins called amphiphysin and dynamin, it is now an endocytic vesicle. At this point, the adapter molecules and clathrin have dissociated, and the receptor is either trafficked back to the plasma membrane or targeted to lysosomes for degradation.
At any point in this process, the β-arrestins may also recruit other proteins—such as the non-receptor tyrosine kinase (nRTK), c-SRC—which may activate ERK1/2, or other mitogen-activated protein kinase (MAPK) signaling through, for example, phosphorylation of the small GTPase, Ras, or recruit the proteins of the ERK cascade directly (i.e., Raf-1, MEK, ERK-1/2) at which point signaling is initiated due to their close proximity to one another. Another target of c-SRC are the dynamin molecules involved in endocytosis. Dynamins polymerize around the neck of an incoming vesicle, and their phosphorylation by c-SRC provides the energy necessary for the conformational change allowing the final "pinching off" from the membrane.
=== GPCR cellular regulation ===
Receptor desensitization is mediated through a combination phosphorylation, β-arr binding, and endocytosis as described above. Downregulation occurs when endocytosed receptor is embedded in an endosome that is trafficked to merge with an organelle called a lysosome. Because lysosomal membranes are rich in proton pumps, their interiors have low pH (≈4.8 vs. the pH≈7.2 cytosol), which acts to denature the GPCRs. In addition, lysosomes contain many degradative enzymes, including proteases, which can function only at such low pH, and so the peptide bonds joining the residues of the GPCR together may be cleaved. Whether or not a given receptor is trafficked to a lysosome, detained in endosomes, or trafficked back to the plasma membrane depends on a variety of factors, including receptor type and magnitude of the signal.
GPCR regulation is additionally mediated by gene transcription factors. These factors can increase or decrease gene transcription and thus increase or decrease the generation of new receptors (up- or down-regulation) that travel to the cell membrane.
== Receptor oligomerization ==
G-protein-coupled receptor oligomerisation is a widespread phenomenon. One of the best-studied examples is the metabotropic GABAB receptor. This so-called constitutive receptor is formed by heterodimerization of GABABR1 and GABABR2 subunits. Expression of the GABABR1 without the GABABR2 in heterologous systems leads to retention of the subunit in the endoplasmic reticulum. Expression of the GABABR2 subunit alone, meanwhile, leads to surface expression of the subunit, although with no functional activity (i.e., the receptor does not bind agonist and cannot initiate a response following exposure to agonist). Expression of the two subunits together leads to plasma membrane expression of functional receptor. It has been shown that GABABR2 binding to GABABR1 causes masking of a retention signal of functional receptors.
== Origin and diversification of the superfamily ==
Signal transduction mediated by the superfamily of GPCRs dates back to the origin of multicellularity. Mammalian-like GPCRs are found in fungi, and have been classified according to the GRAFS classification system based on GPCR fingerprints. Identification of the superfamily members across the eukaryotic domain, and comparison of the family-specific motifs, have shown that the superfamily of GPCRs have a common origin. Characteristic motifs indicate that three of the five GRAFS families, Rhodopsin, Adhesion, and Frizzled, evolved from the Dictyostelium discoideum cAMP receptors before the split of opisthokonts. Later, the Secretin family evolved from the Adhesion GPCR receptor family before the split of nematodes. Insect GPCRs appear to be in their own group and Taste2 is identified as descending from Rhodopsin. Note that the Secretin/Adhesion split is based on presumed function rather than signature, as the classical Class B (7tm_2, Pfam PF00002) is used to identify both in the studies.
== See also ==
G protein-coupled receptors database
List of MeSH codes (D12.776)
Metabotropic receptor
Orphan receptor
Pepducins, a class of drug candidates targeted at GPCRs
Receptor activated solely by a synthetic ligand, a technique for control of cell signaling through synthetic GPCRs
TOG superfamily
== References ==
== Further reading ==
Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (April 2003). "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America. 100 (8): 4903–8. Bibcode:2003PNAS..100.4903V. doi:10.1073/pnas.0230374100. PMC 153653. PMID 12679517.
"GPCR Reference Library". Retrieved 11 August 2008. Reference for molecular and mathematical models for the initial receptor response
"The Nobel Prize in Chemistry 2012" (PDF). Archived (PDF) from the original on 18 October 2012. Retrieved 10 October 2012.
== External links ==
G-protein-coupled+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
GPCR Cell Line Archived 3 April 2015 at the Wayback Machine
"IUPHAR/BPS Guide to PHARMACOLOGY Database (GPCRs)". IUPHAR Database. University of Edinburgh / International Union of Basic and Clinical Pharmacology. Retrieved 6 February 2019.
"GPCRdb". Data, diagrams and web tools for G protein-coupled receptors (GPCRs).; Munk C, Isberg V, Mordalski S, Harpsøe K, Rataj K, Hauser AS, et al. (July 2016). "GPCRdb: the G protein-coupled receptor database - an introduction". British Journal of Pharmacology. 173 (14): 2195–207. doi:10.1111/bph.13509. PMC 4919580. PMID 27155948.
"G Protein-Coupled Receptors on the NET". Archived from the original on 23 July 2011. Retrieved 10 November 2010. a classification of GPCRs
"PSI GPCR Network Center". Archived from the original on 25 July 2013. Retrieved 11 July 2013. a Protein Structure Initiative:Biology Network Center aimed at determining the 3D structures of representative GPCR family proteins
GPCR-HGmod Archived 1 February 2016 at the Wayback Machine, a database of 3D structural models of all human G-protein coupled receptors, built by the GPCR-I-TASSER pipeline Zhang J, Yang J, Jang R, Zhang Y (August 2015). "GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome". Structure. 23 (8): 1538–1549. doi:10.1016/j.str.2015.06.007. PMC 4526412. PMID 26190572. | Wikipedia/G_protein–coupled_receptor |
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.
Plasma lipoprotein particles are commonly divided into five main classes, based on size, lipid composition, and apolipoprotein content. They are, in increasing size order: HDL, LDL, IDL, VLDL and chylomicrons. Subgroups of these plasma particles are primary drivers or modulators of atherosclerosis.
Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are sometimes also classified as lipoproteins, since they are formed by lipids and proteins.
== Scope ==
=== Transmembrane lipoproteins ===
Some transmembrane proteolipids, especially those found in bacteria, are referred to as lipoproteins; they are not related to the lipoprotein particles that this article is about. Such transmembrane proteins are difficult to isolate, as they bind tightly to the lipid membrane, often require lipids to display the proper structure, and can be water-insoluble. Detergents are usually required to isolate transmembrane lipoproteins from their associated biological membranes.
=== Plasma lipoprotein particles ===
Because fats are insoluble in water, they cannot be transported on their own in extracellular water, including blood plasma. Instead, they are surrounded by a hydrophilic external shell that functions as a transport vehicle. The role of lipoprotein particles is to transport fat molecules, such as triglycerides, phospholipids, and cholesterol within the extracellular water of the body to all the cells and tissues of the body. The proteins included in the external shell of these particles, called apolipoproteins, are synthesized and secreted into the extracellular water by both the small intestine and liver cells. The external shell also contains phospholipids and cholesterol.
All cells use and rely on fats and cholesterol as building blocks to create the multiple membranes that cells use both to control internal water content and internal water-soluble elements and to organize their internal structure and protein enzymatic systems. The outer shell of lipoprotein particles have the hydrophilic groups of phospholipids, cholesterol, and apolipoproteins directed outward. Such characteristics make them soluble in the salt-water-based blood pool. Triglycerides and cholesteryl esters are carried internally, shielded from the water by the outer shell. The kind of apolipoproteins contained in the outer shell determines the functional identity of the lipoprotein particles. The interaction of these apolipoproteins with enzymes in the blood, with each other, or with specific proteins on the surfaces of cells, determines whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles.
Characterization in human plasma
== Structure ==
Lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids, primarily cholesteryl esters and triglycerides. This hydrophobic core is surrounded by a hydrophilic membrane consisting of phospholipids, free cholesterol, and apolipoproteins. Plasma lipoproteins, found in blood plasma, are typically divided into five main classes based on size, lipid composition, and apolipoprotein content: HDL, LDL, IDL, VLDL and chylomicrons.
== Functions ==
=== Metabolism ===
The handling of lipoprotein particles in the body is referred to as lipoprotein particle metabolism. It is divided into two pathways, exogenous and endogenous, depending in large part on whether the lipoprotein particles in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous), through de novo synthesis of triglycerides.
The hepatocytes are the main platform for the handling of triglycerides and cholesterol; the liver can also store certain amounts of glycogen and triglycerides. While adipocytes are the main storage cells for triglycerides, they do not produce any lipoproteins.
==== Exogenous pathway ====
Bile emulsifies fats contained in the chyme, then pancreatic lipase cleaves triglyceride molecules into two fatty acids and one 2-monoacylglycerol. Enterocytes readily absorb the small molecules from the chymus. Inside of the enterocytes, fatty acids and monoacylglycerides are transformed again into triglycerides. Then these lipids are assembled with apolipoprotein B-48 into nascent chylomicrons. These particles are then secreted into the lacteals in a process that depends heavily on apolipoprotein B-48. As they circulate through the lymphatic vessels, nascent chylomicrons bypass the liver circulation and are drained via the thoracic duct into the bloodstream.
In the blood stream, nascent chylomicron particles interact with HDL particles, resulting in HDL donation of apolipoprotein C-II and apolipoprotein E to the nascent chylomicron. The chylomicron at this stage is then considered mature. Via apolipoprotein C-II, mature chylomicrons activate lipoprotein lipase (LPL), an enzyme on endothelial cells lining the blood vessels. LPL catalyzes the hydrolysis of triglycerides that ultimately releases glycerol and fatty acids from the chylomicrons. Glycerol and fatty acids can then be absorbed in peripheral tissues, especially adipose and muscle, for energy and storage.
The hydrolyzed chylomicrons are now called chylomicron remnants. The chylomicron remnants continue circulating the bloodstream until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the endocytosis of the chylomicron remnants, which are subsequently hydrolyzed within lysosomes. Lysosomal hydrolysis releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use.
==== Endogenous pathway ====
The liver is the central platform for the handling of lipids: it is able to store glycerols and fats in its cells, the hepatocytes. Hepatocytes are also able to create triglycerides via de novo synthesis. They also produce the bile from cholesterol. The intestines are responsible for absorbing cholesterol. They transfer it over into the blood stream.
In the hepatocytes, triglycerides and cholesteryl esters are assembled with apolipoprotein B-100 to form nascent VLDL particles. Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B-100.
In the blood stream, nascent VLDL particles bump with HDL particles; as a result, HDL particles donate apolipoprotein C-II and apolipoprotein E to the nascent VLDL particle. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature. VLDL particles circulate and encounter LPL expressed on endothelial cells. Apolipoprotein C-II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or intermediate-density lipoproteins (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by hepatic lipase.
Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind IDL remnants, called low-density lipoproteins (LDL), which contain a relatively high cholesterol content (see native LDL structure at 37°C on YouTube). LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the LDL receptor and apolipoprotein B-100 on the LDL particle. Absorption occurs through endocytosis, and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.
=== Possible role in oxygen transport ===
Plasma lipoproteins may carry oxygen gas. This property is due to the crystalline hydrophobic structure of lipids, providing a suitable environment for O2 solubility compared to an aqueous medium.
=== Role in inflammation ===
Inflammation, a biological system response to stimuli such as the introduction of a pathogen, has an underlying role in numerous systemic biological functions and pathologies. This is a useful response by the immune system when the body is exposed to pathogens, such as bacteria in locations that will prove harmful, but can also have detrimental effects if left unregulated. It has been demonstrated that lipoproteins, specifically HDL, have important roles in the inflammatory process.
When the body is functioning under normal, stable physiological conditions, HDL has been shown to be beneficial in several ways. LDL contains apolipoprotein B (apoB), which allows LDL to bind to different tissues, such as the artery wall if the glycocalyx has been damaged by high blood sugar levels. If oxidised, the LDL can become trapped in the proteoglycans, preventing its removal by HDL cholesterol efflux. Normal functioning HDL is able to prevent the process of oxidation of LDL and the subsequent inflammatory processes seen after oxidation.
Lipopolysaccharide, or LPS, is the major pathogenic factor on the cell wall of Gram-negative bacteria. Gram-positive bacteria has a similar component named Lipoteichoic acid, or LTA. HDL has the ability to bind LPS and LTA, creating HDL-LPS complexes to neutralize the harmful effects in the body and clear the LPS from the body. HDL also has significant roles interacting with cells of the immune system to modulate the availability of cholesterol and modulate the immune response.
Under certain abnormal physiological conditions such as system infection or sepsis, the major components of HDL become altered, The composition and quantity of lipids and apolipoproteins are altered as compared to normal physiological conditions, such as a decrease in HDL cholesterol (HDL-C), phospholipids, apoA-I (a major lipoprotein in HDL that has been shown to have beneficial anti-inflammatory properties), and an increase in Serum amyloid A. This altered composition of HDL is commonly referred to as acute-phase HDL in an acute-phase inflammatory response, during which time HDL can lose its ability to inhibit the oxidation of LDL. In fact, this altered composition of HDL is associated with increased mortality and worse clinical outcomes in patients with sepsis.
== Classification ==
=== By density ===
Lipoproteins may be classified as five major groups, listed from larger and lower density to smaller and higher density. Lipoproteins are larger and less dense when the fat to protein ratio is increased. They are classified on the basis of electrophoresis, ultracentrifugation and nuclear magnetic resonance spectroscopy via the Vantera Analyzer.
Chylomicrons carry triglycerides (fat) from the intestines to the liver, to skeletal muscle, and to adipose tissue.
Very-low-density lipoproteins (VLDL) carry (newly synthesised) triglycerides from the liver to adipose tissue.
Intermediate-density lipoproteins (IDL) are intermediate between VLDL and LDL. They are not usually detectable in the blood when fasting.
Low-density lipoproteins (LDL) carry 3,000 to 6,000 fat molecules (phospholipids, cholesterol, triglycerides, etc.) around the body. LDL particles are sometimes referred to as "bad" lipoprotein because concentrations of two kinds of LDL (sd-LDL and LPA), correlate with atherosclerosis progression. In healthy individuals, most LDL is large and buoyant (lb LDL).
large buoyant LDL (lb LDL) particles
small dense LDL (sd LDL) particles
Lipoprotein(a) (LPA) is a lipoprotein particle of a certain phenotype
High-density lipoproteins (HDL) collect fat molecules from the body's cells/tissues and take them back to the liver. HDLs are sometimes referred to as "good" lipoprotein because higher concentrations correlate with low rates of atherosclerosis progression and/or regression.
For young healthy research subjects, ~70 kg (154 lb), these data represent averages across individuals studied, percentages represent % dry weight:
However, these data are not necessarily reliable for any one individual or for the general clinical population.
=== Alpha and beta ===
It is also possible to classify lipoproteins as "alpha" and "beta", according to the classification of proteins in serum protein electrophoresis. This terminology is sometimes used in describing lipid disorders such as abetalipoproteinemia.
=== Subdivisions ===
Lipoproteins, such as LDL and HDL, can be further subdivided into subspecies isolated through a variety of methods. These are subdivided by density or by the protein contents/ proteins they carry. While the research is currently ongoing, researchers are learning that different subspecies contain different apolipoproteins, proteins, and lipid contents between species which have different physiological roles. For example, within the HDL lipoprotein subspecies, a large number of proteins are involved in general lipid metabolism. However, it is being elucidated that HDL subspecies also contain proteins involved in the following functions: homeostasis, fibrinogen, clotting cascade, inflammatory and immune responses, including the complement system, proteolysis inhibitors, acute-phase response proteins, and the LPS-binding protein, heme and iron metabolism, platelet regulation, vitamin binding and general transport.
== Research ==
High levels of lipoprotein(a) are a significant risk factor for atherosclerotic cardiovascular diseases via mechanisms associated with inflammation and thrombosis. The links of mechanisms between different lipoprotein isoforms and risk for cardiovascular diseases, lipoprotein synthesis, regulation, and metabolism, and related risks for genetic diseases are under active research, as of 2022.
== See also ==
Lipid anchored protein
Remnant cholesterol
Reverse cholesterol transport
Vertical Auto Profile
== References ==
== External links ==
Lipoproteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH) | Wikipedia/Lipoprotein |
A single-pass membrane protein also known as single-spanning protein or bitopic protein is a transmembrane protein that spans the lipid bilayer only once. These proteins may constitute up to 50% of all transmembrane proteins, depending on the organism, and contribute significantly to the network of interactions between different proteins in cells, including interactions via transmembrane alpha helices. They usually include one or several water-soluble domains situated at the different sides of biological membranes, for example in single-pass transmembrane receptors. Some of them are small and serve as regulatory or structure-stabilizing subunits in large multi-protein transmembrane complexes, such as photosystems or the respiratory chain. More than 2300 single-pass membrane proteins were identified in the human genome.
== Topology-based classification ==
Bitopic proteins are classified into 4 types, depending on their transmembrane topology and location of the transmembrane helix in the amino acid sequence of the protein. According to Uniprot:
Type I: N-terminus on the extracellular side of the membrane; removed signal peptide
Type II: N-terminus on the cytoplasmic side of the membrane; transmembrane helix located close to the N-terminus, where it works as an anchor
Type III: N-terminus on the extracellular side of the membrane; no signal peptide
Type IV: N-terminus on the cytoplasmic side of the membrane; transmembrane helix located close to the C-terminus, where it works as an anchor
Hence type I proteins are anchored to the lipid membrane with a stop-transfer anchor sequence and have their N-terminal domains targeted to the ER lumen during synthesis. Type II and III are anchored with a signal-anchor sequence, with type II being targeted to the ER lumen with its C-terminal domain, while type III have their N-terminal domains targeted to the ER lumen.
== Structure ==
A single-pass transmembrane protein typically consists of three domains, the extracellular domain, the transmembrane domain, and the intracellular domain. The transmembrane domain is the smallest at around 25 amino acid residues and forms an alpha helix inserted into the membrane bilayer. The ECD is typically much larger than the ICD and is often globular, whereas many ICDs have relatively high disorder. Some proteins in this class function as monomers, but dimerization or higher-order oligomerization is common.
== Evolution ==
The number of single-pass transmembrane proteins in an organism's genome varies significantly. It is higher in eukaryotes than prokaryotes and in multicellular than unicellular organisms. The fraction of proteins in this class is larger in humans than in the model organisms Danio rerio (zebrafish) and Caenorhabditis elegans (nematode worms), suggesting that genes encoding these proteins have undergone expansion in the vertebrate and mammalian lineages.
== Databases ==
Membranome database is a database of bitopic proteins from several model organisms.
Bitopic proteins in OPM database
== References == | Wikipedia/Single-pass_membrane_protein |
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops (three extracellular loops interacting with ligand molecules, three intracellular loops interacting with G proteins, an N-terminal extracellular region and a C-terminal intracellular region) of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (rhodopsin-like family). They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.
G protein-coupled receptors are found only in eukaryotes, including yeast, and choanoflagellates. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters. They vary in size from small molecules to peptides, to large proteins. G protein-coupled receptors are involved in many diseases.
There are two principal signal transduction pathways involving the G protein-coupled receptors:
the cAMP signal pathway and
the phosphatidylinositol signal pathway.
When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs, Gαi/o, Gαq/11, Gα12/13).: 1160
GPCRs are an important drug target, and approximately 34% of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018. It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of the pharmaceutical research.
== History and significance ==
With the determination of the first structure of the complex between a G-protein coupled receptor (GPCR) and a G-protein trimer (Gαβγ) in 2011 a new chapter of GPCR research was opened for structural investigations of global switches with more than one protein being investigated. The previous breakthroughs involved determination of the crystal structure of the first GPCR, rhodopsin, in 2000 and the crystal structure of the first GPCR with a diffusible ligand (β2AR) in 2007. The way in which the seven transmembrane helices of a GPCR are arranged into a bundle was suspected based on the low-resolution model of frog rhodopsin from cryogenic electron microscopy studies of the two-dimensional crystals. The crystal structure of rhodopsin, that came up three years later, was not a surprise apart from the presence of an additional cytoplasmic helix H8 and a precise location of a loop covering retinal binding site. However, it provided a scaffold which was hoped to be a universal template for homology modeling and drug design for other GPCRs – a notion that proved to be too optimistic.
Results 7 years later were surprising because the crystallization of β2-adrenergic receptor (β2AR) with a diffusible ligand revealed quite a different shape of the receptor extracellular side than that of rhodopsin. This area is important because it is responsible for the ligand binding and is targeted by many drugs. Moreover, the ligand binding site was much more spacious than in the rhodopsin structure and was open to the exterior. In the other receptors crystallized shortly afterwards the binding side was even more easily accessible to the ligand. New structures complemented with biochemical investigations uncovered mechanisms of action of molecular switches which modulate the structure of the receptor leading to activation states for agonists or to complete or partial inactivation states for inverse agonists.
The 2012 Nobel Prize in Chemistry was awarded to Brian Kobilka and Robert Lefkowitz for their work that was "crucial for understanding how G protein-coupled receptors function". There have been at least seven other Nobel Prizes awarded for some aspect of G protein–mediated signaling. As of 2012, two of the top ten global best-selling drugs (Advair Diskus and Abilify) act by targeting G protein-coupled receptors.
== Classification ==
The exact size of the GPCR superfamily is unknown, but at least 831 different human genes (or about 4% of the entire protein-coding genome) have been predicted to code for them from genome sequence analysis. Although numerous classification schemes have been proposed, the superfamily was classically divided into three main classes (A, B, and C) with no detectable shared sequence homology between classes.
The largest class by far is class A, which accounts for nearly 85% of the GPCR genes. Of class A GPCRs, over half of these are predicted to encode olfactory receptors, while the remaining receptors are liganded by known endogenous compounds or are classified as orphan receptors. Despite the lack of sequence homology between classes, all GPCRs have a common structure and mechanism of signal transduction. The very large rhodopsin A group has been further subdivided into 19 subgroups (A1-A19).
According to the classical A-F system, GPCRs can be grouped into six classes based on sequence homology and functional similarity:
Class A (or 1) (Rhodopsin-like)
Class B (or 2) (Secretin receptor family)
Class C (or 3) (Metabotropic glutamate/pheromone)
Class D (or 4) (Fungal mating pheromone receptors)
Class E (or 5) (Cyclic AMP receptors)
Class F (or 6) (Frizzled/Smoothened)
More recently, an alternative classification system called GRAFS (Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, Secretin) has been proposed for vertebrate GPCRs. They correspond to classical classes C, A, B2, F, and B.
An early study based on available DNA sequence suggested that the human genome encodes roughly 750 G protein-coupled receptors, about 350 of which detect hormones, growth factors, and other endogenous ligands. Approximately 150 of the GPCRs found in the human genome have unknown functions.
Some web-servers and bioinformatics prediction methods have been used for predicting the classification of GPCRs according to their amino acid sequence alone, by means of the pseudo amino acid composition approach.
== Physiological roles ==
GPCRs are involved in a wide variety of physiological processes. Some examples of their physiological roles include:
The visual sense: The opsins use a photoisomerization reaction to translate electromagnetic radiation into cellular signals. Rhodopsin, for example, uses the conversion of 11-cis-retinal to all-trans-retinal for this purpose.
The gustatory sense (taste): GPCRs in taste cells mediate release of gustducin in response to bitter-, umami- and sweet-tasting substances.
The sense of smell: Receptors of the olfactory epithelium bind odorants (olfactory receptors) and pheromones (vomeronasal receptors)
Behavioral and mood regulation: Receptors in the mammalian brain bind several different neurotransmitters, including serotonin, dopamine, histamine, GABA, and glutamate
Regulation of immune system activity and inflammation: chemokine receptors bind ligands that mediate intercellular communication between cells of the immune system; receptors such as histamine receptors bind inflammatory mediators and engage target cell types in the inflammatory response. GPCRs are also involved in immune-modulation, e. g. regulating interleukin induction or suppressing TLR-induced immune responses from T cells.
Autonomic nervous system transmission: Both the sympathetic and parasympathetic nervous systems are regulated by GPCR pathways, responsible for control of many automatic functions of the body such as blood pressure, heart rate, and digestive processes
Cell density sensing: A novel GPCR role in regulating cell density sensing.
Homeostasis modulation (e.g., water balance).
Involved in growth and metastasis of some types of tumors.
Used in the endocrine system for peptide and amino-acid derivative hormones that bind to GCPRs on the cell membrane of a target cell. This activates cAMP, which in turn activates several kinases, allowing for a cellular response, such as transcription.
== Receptor structure ==
GPCRs are integral membrane proteins that possess seven membrane-spanning domains or transmembrane helices. The extracellular parts of the receptor can be glycosylated. These extracellular loops also contain two highly conserved cysteine residues that form disulfide bonds to stabilize the receptor structure. Some seven-transmembrane helix proteins (channelrhodopsin) that resemble GPCRs may contain ion channels, within their protein.
In 2000, the first crystal structure of a mammalian GPCR, that of bovine rhodopsin (1F88), was solved. In 2007, the first structure of a human GPCR was solved This human β2-adrenergic receptor GPCR structure proved highly similar to the bovine rhodopsin. The structures of activated or agonist-bound GPCRs have also been determined. These structures indicate how ligand binding at the extracellular side of a receptor leads to conformational changes in the cytoplasmic side of the receptor. The biggest change is an outward movement of the cytoplasmic part of the 5th and 6th transmembrane helix (TM5 and TM6). The structure of activated beta-2 adrenergic receptor in complex with Gs confirmed that the Gα binds to a cavity created by this movement.
GPCRs exhibit a similar structure to some other proteins with seven transmembrane domains, such as microbial rhodopsins and adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2). However, these 7TMH (7-transmembrane helices) receptors and channels do not associate with G proteins. In addition, ADIPOR1 and ADIPOR2 are oriented oppositely to GPCRs in the membrane (i.e. GPCRs usually have an extracellular N-terminus, cytoplasmic C-terminus, whereas ADIPORs are inverted).
== Structure–function relationships ==
In terms of structure, GPCRs are characterized by an extracellular N-terminus, followed by seven transmembrane (7-TM) α-helices (TM-1 to TM-7) connected by three intracellular (IL-1 to IL-3) and three extracellular loops (EL-1 to EL-3), and finally an intracellular C-terminus. The GPCR arranges itself into a tertiary structure resembling a barrel, with the seven transmembrane helices forming a cavity within the plasma membrane that serves a ligand-binding domain that is often covered by EL-2. Ligands may also bind elsewhere, however, as is the case for bulkier ligands (e.g., proteins or large peptides), which instead interact with the extracellular loops, or, as illustrated by the class C metabotropic glutamate receptors (mGluRs), the N-terminal tail. The class C GPCRs are distinguished by their large N-terminal tail, which also contains a ligand-binding domain. Upon glutamate-binding to an mGluR, the N-terminal tail undergoes a conformational change that leads to its interaction with the residues of the extracellular loops and TM domains. The eventual effect of all three types of agonist-induced activation is a change in the relative orientations of the TM helices (likened to a twisting motion) leading to a wider intracellular surface and "revelation" of residues of the intracellular helices and TM domains crucial to signal transduction function (i.e., G-protein coupling). Inverse agonists and antagonists may also bind to a number of different sites, but the eventual effect must be prevention of this TM helix reorientation.
The structure of the N- and C-terminal tails of GPCRs may also serve important functions beyond ligand-binding. For example, The C-terminus of M3 muscarinic receptors is sufficient, and the six-amino-acid polybasic (KKKRRK) domain in the C-terminus is necessary for its preassembly with Gq proteins. In particular, the C-terminus often contains serine (Ser) or threonine (Thr) residues that, when phosphorylated, increase the affinity of the intracellular surface for the binding of scaffolding proteins called β-arrestins (β-arr). Once bound, β-arrestins both sterically prevent G-protein coupling and may recruit other proteins, leading to the creation of signaling complexes involved in extracellular-signal regulated kinase (ERK) pathway activation or receptor endocytosis (internalization). As the phosphorylation of these Ser and Thr residues often occurs as a result of GPCR activation, the β-arr-mediated G-protein-decoupling and internalization of GPCRs are important mechanisms of desensitization. In addition, internalized "mega-complexes" consisting of a single GPCR, β-arr(in the tail conformation), and heterotrimeric G protein exist and may account for protein signaling from endosomes.
A final common structural theme among GPCRs is palmitoylation of one or more sites of the C-terminal tail or the intracellular loops. Palmitoylation is the covalent modification of cysteine (Cys) residues via addition of hydrophobic acyl groups, and has the effect of targeting the receptor to cholesterol- and sphingolipid-rich microdomains of the plasma membrane called lipid rafts. As many of the downstream transducer and effector molecules of GPCRs (including those involved in negative feedback pathways) are also targeted to lipid rafts, this has the effect of facilitating rapid receptor signaling.
GPCRs respond to extracellular signals mediated by a huge diversity of agonists, ranging from proteins to biogenic amines to protons, but all transduce this signal via a mechanism of G-protein coupling. This is made possible by a guanine-nucleotide exchange factor (GEF) domain primarily formed by a combination of IL-2 and IL-3 along with adjacent residues of the associated TM helices.
== Mechanism ==
The G protein-coupled receptor is activated by an external signal in the form of a ligand or other signal mediator. This creates a conformational change in the receptor, causing activation of a G protein. Further effect depends on the type of G protein. G proteins are subsequently inactivated by GTPase activating proteins, known as RGS proteins.
=== Ligand binding ===
GPCRs include one or more receptors for the following ligands:
sensory signal mediators (e.g., light and olfactory stimulatory molecules);
adenosine, bombesin, bradykinin, endothelin, γ-aminobutyric acid (GABA), hepatocyte growth factor (HGF), melanocortins, neuropeptide Y, opioid peptides, opsins, somatostatin, GH, tachykinins, members of the vasoactive intestinal peptide family, and vasopressin;
biogenic amines (e.g., dopamine, epinephrine, norepinephrine, histamine, serotonin, and melatonin);
glutamate (metabotropic effect);
glucagon;
acetylcholine (muscarinic effect);
chemokines;
lipid mediators of inflammation (e.g., prostaglandins, prostanoids, platelet-activating factor, and leukotrienes);
peptide hormones (e.g., calcitonin, C5a anaphylatoxin, follicle-stimulating hormone [FSH], gonadotropin-releasing hormone [GnRH], neurokinin, thyrotropin-releasing hormone [TRH], and oxytocin);
and endocannabinoids.
GPCRs that act as receptors for stimuli that have not yet been identified are known as orphan receptors.
However, in contrast to other types of receptors that have been studied, wherein ligands bind externally to the membrane, the ligands of GPCRs typically bind within the transmembrane domain. However, protease-activated receptors are activated by cleavage of part of their extracellular domain.
=== Conformational change ===
The transduction of the signal through the membrane by the receptor is not completely understood. It is known that in the inactive state, the GPCR is bound to a heterotrimeric G protein complex. Binding of an agonist to the GPCR results in a conformational change in the receptor that is transmitted to the bound Gα subunit of the heterotrimeric G protein via protein domain dynamics. The activated Gα subunit exchanges GTP in place of GDP which in turn triggers the dissociation of Gα subunit from the Gβγ dimer and from the receptor. The dissociated Gα and Gβγ subunits interact with other intracellular proteins to continue the signal transduction cascade while the freed GPCR is able to rebind to another heterotrimeric G protein to form a new complex that is ready to initiate another round of signal transduction.
It is believed that a receptor molecule exists in a conformational equilibrium between active and inactive biophysical states. The binding of ligands to the receptor may shift the equilibrium toward the active receptor states. Three types of ligands exist: Agonists are ligands that shift the equilibrium in favour of active states; inverse agonists are ligands that shift the equilibrium in favour of inactive states; and neutral antagonists are ligands that do not affect the equilibrium. It is not yet known how exactly the active and inactive states differ from each other.
=== G-protein activation/deactivation cycle ===
When the receptor is inactive, the GEF domain may be bound to an also inactive α-subunit of a heterotrimeric G-protein. These "G-proteins" are a trimer of α, β, and γ subunits (known as Gα, Gβ, and Gγ, respectively) that is rendered inactive when reversibly bound to Guanosine diphosphate (GDP) (or, alternatively, no guanine nucleotide) but active when bound to guanosine triphosphate (GTP). Upon receptor activation, the GEF domain, in turn, allosterically activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein's α-subunit. The cell maintains a 10:1 ratio of cytosolic GTP:GDP so exchange for GTP is ensured. At this point, the subunits of the G-protein dissociate from the receptor, as well as each other, to yield a Gα-GTP monomer and a tightly interacting Gβγ dimer, which are now free to modulate the activity of other intracellular proteins. The extent to which they may diffuse, however, is limited due to the palmitoylation of Gα and the presence of an isoprenoid moiety that has been covalently added to the C-termini of Gγ.
Because Gα also has slow GTP→GDP hydrolysis capability, the inactive form of the α-subunit (Gα-GDP) is eventually regenerated, thus allowing reassociation with a Gβγ dimer to form the "resting" G-protein, which can again bind to a GPCR and await activation. The rate of GTP hydrolysis is often accelerated due to the actions of another family of allosteric modulating proteins called regulators of G-protein signaling, or RGS proteins, which are a type of GTPase-activating protein, or GAP. In fact, many of the primary effector proteins (e.g., adenylate cyclases) that become activated/inactivated upon interaction with Gα-GTP also have GAP activity. Thus, even at this early stage in the process, GPCR-initiated signaling has the capacity for self-termination.
=== Crosstalk ===
GPCRs downstream signals have been shown to possibly interact with integrin signals, such as FAK. Integrin signaling will phosphorylate FAK, which can then decrease GPCR Gαs activity.
== Signaling ==
If a receptor in an active state encounters a G protein, it may activate it. Some evidence suggests that receptors and G proteins are actually pre-coupled. For example, binding of G proteins to receptors affects the receptor's affinity for ligands. Activated G proteins are bound to GTP.
Further signal transduction depends on the type of G protein. The enzyme adenylate cyclase is an example of a cellular protein that can be regulated by a G protein, in this case the G protein Gs. Adenylate cyclase activity is activated when it binds to a subunit of the activated G protein. Activation of adenylate cyclase ends when the G protein returns to the GDP-bound state.
Adenylate cyclases (of which 9 membrane-bound and one cytosolic forms are known in humans) may also be activated or inhibited in other ways (e.g., Ca2+/calmodulin binding), which can modify the activity of these enzymes in an additive or synergistic fashion along with the G proteins.
The signaling pathways activated through a GPCR are limited by the primary sequence and tertiary structure of the GPCR itself but ultimately determined by the particular conformation stabilized by a particular ligand, as well as the availability of transducer molecules. Currently, GPCRs are considered to utilize two primary types of transducers: G-proteins and β-arrestins. Because β-arr's have high affinity only to the phosphorylated form of most GPCRs (see above or below), the majority of signaling is ultimately dependent upon G-protein activation. However, the possibility for interaction does allow for G-protein-independent signaling to occur.
=== G-protein-dependent signaling ===
There are three main G-protein-mediated signaling pathways, mediated by four sub-classes of G-proteins distinguished from each other by sequence homology (Gαs, Gαi/o, Gαq/11, and Gα12/13). Each sub-class of G-protein consists of multiple proteins, each the product of multiple genes or splice variations that may imbue them with differences ranging from subtle to distinct with regard to signaling properties, but in general they appear reasonably grouped into four classes. Because the signal transducing properties of the various possible βγ combinations do not appear to radically differ from one another, these classes are defined according to the isoform of their α-subunit.: 1163
While most GPCRs are capable of activating more than one Gα-subtype, they also show a preference for one subtype over another. When the subtype activated depends on the ligand that is bound to the GPCR, this is called functional selectivity (also known as agonist-directed trafficking, or conformation-specific agonism). However, the binding of any single particular agonist may also initiate activation of multiple different G-proteins, as it may be capable of stabilizing more than one conformation of the GPCR's GEF domain, even over the course of a single interaction. In addition, a conformation that preferably activates one isoform of Gα may activate another if the preferred is less available. Furthermore, feedback pathways may result in receptor modifications (e.g., phosphorylation) that alter the G-protein preference. Regardless of these various nuances, the GPCR's preferred coupling partner is usually defined according to the G-protein most obviously activated by the endogenous ligand under most physiological or experimental conditions.
==== Gα signaling ====
The effector of both the Gαs and Gαi/o pathways is the cyclic-adenosine monophosphate (cAMP)-generating enzyme adenylate cyclase, or AC. While there are ten different AC gene products in mammals, each with subtle differences in tissue distribution or function, all catalyze the conversion of cytosolic adenosine triphosphate (ATP) to cAMP, and all are directly stimulated by G-proteins of the Gαs class. In contrast, however, interaction with Gα subunits of the Gαi/o type inhibits AC from generating cAMP. Thus, a GPCR coupled to Gαs counteracts the actions of a GPCR coupled to Gαi/o, and vice versa. The level of cytosolic cAMP may then determine the activity of various ion channels as well as members of the ser/thr-specific protein kinase A (PKA) family. Thus cAMP is considered a second messenger and PKA a secondary effector.
The effector of the Gαq/11 pathway is phospholipase C-β (PLCβ), which catalyzes the cleavage of membrane-bound phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers inositol (1,4,5) trisphosphate (IP3) and diacylglycerol (DAG). IP3 acts on IP3 receptors found in the membrane of the endoplasmic reticulum (ER) to elicit Ca2+ release from the ER, while DAG diffuses along the plasma membrane where it may activate any membrane localized forms of a second ser/thr kinase called protein kinase C (PKC). Since many isoforms of PKC are also activated by increases in intracellular Ca2+, both these pathways can also converge on each other to signal through the same secondary effector. Elevated intracellular Ca2+ also binds and allosterically activates proteins called calmodulins, which in turn tosolic small GTPase, Rho. Once bound to GTP, Rho can then go on to activate various proteins responsible for cytoskeleton regulation such as Rho-kinase (ROCK). Most GPCRs that couple to Gα12/13 also couple to other sub-classes, often Gαq/11.
==== Gβγ signaling ====
The above descriptions ignore the effects of Gβγ–signalling, which can also be important, in particular in the case of activated Gαi/o-coupled GPCRs. The primary effectors of Gβγ are various ion channels, such as G-protein-regulated inwardly rectifying K+ channels (GIRKs), P/Q- and N-type voltage-gated Ca2+ channels, as well as some isoforms of AC and PLC, along with some phosphoinositide-3-kinase (PI3K) isoforms.
=== G-protein-independent signaling ===
Although they are classically thought of working only together, GPCRs may signal through G-protein-independent mechanisms, and heterotrimeric G-proteins may play functional roles independent of GPCRs. GPCRs may signal independently through many proteins already mentioned for their roles in G-protein-dependent signaling such as β-arrs, GRKs, and Srcs. Such signaling has been shown to be physiologically relevant, for example, β-arrestin signaling mediated by the chemokine receptor CXCR3 was necessary for full efficacy chemotaxis of activated T cells. In addition, further scaffolding proteins involved in subcellular localization of GPCRs (e.g., PDZ-domain-containing proteins) may also act as signal transducers. Most often the effector is a member of the MAPK family.
==== Examples ====
In the late 1990s, evidence began accumulating to suggest that some GPCRs are able to signal without G proteins. The ERK2 mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many pathways, has been shown to be activated in response to cAMP-mediated receptor activation in the slime mold D. discoideum despite the absence of the associated G protein α- and β-subunits.
In mammalian cells, the much-studied β2-adrenoceptor has been demonstrated to activate the ERK2 pathway after arrestin-mediated uncoupling of G-protein-mediated signaling. Therefore, it seems likely that some mechanisms previously believed related purely to receptor desensitisation are actually examples of receptors switching their signaling pathway, rather than simply being switched off.
In kidney cells, the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine-phosphorylated ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is necessary to mediate this interaction and subsequently the antiproliferative effect of bradykinin.
==== GPCR-independent signaling by heterotrimeric G-proteins ====
Although it is a relatively immature area of research, it appears that heterotrimeric G-proteins may also take part in non-GPCR signaling. There is evidence for roles as signal transducers in nearly all other types of receptor-mediated signaling, including integrins, receptor tyrosine kinases (RTKs), cytokine receptors (JAK/STATs), as well as modulation of various other "accessory" proteins such as GEFs, guanine-nucleotide dissociation inhibitors (GDIs) and protein phosphatases. There may even be specific proteins of these classes whose primary function is as part of GPCR-independent pathways, termed activators of G-protein signalling (AGS). Both the ubiquity of these interactions and the importance of Gα vs. Gβγ subunits to these processes are still unclear.
== Details of cAMP and PIP2 pathways ==
There are two principal signal transduction pathways involving the G protein-linked receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway.
=== cAMP signal pathway ===
The cAMP signal transduction contains five main characters: stimulative hormone receptor (Rs) or inhibitory hormone receptor (Ri); stimulative regulative G-protein (Gs) or inhibitory regulative G-protein (Gi); adenylyl cyclase; protein kinase A (PKA); and cAMP phosphodiesterase.
Stimulative hormone receptor (Rs) is a receptor that can bind with stimulative signal molecules, while inhibitory hormone receptor (Ri) is a receptor that can bind with inhibitory signal molecules.
Stimulative regulative G-protein is a G-protein linked to stimulative hormone receptor (Rs), and its α subunit upon activation could stimulate the activity of an enzyme or other intracellular metabolism. On the contrary, inhibitory regulative G-protein is linked to an inhibitory hormone receptor, and its α subunit upon activation could inhibit the activity of an enzyme or other intracellular metabolism.
Adenylyl cyclase is a 12-transmembrane glycoprotein that catalyzes the conversion of ATP to cAMP with the help of cofactor Mg2+ or Mn2+. The cAMP produced is a second messenger in cellular metabolism and is an allosteric activator of protein kinase A.
Protein kinase A is an important enzyme in cell metabolism due to its ability to regulate cell metabolism by phosphorylating specific committed enzymes in the metabolic pathway. It can also regulate specific gene expression, cellular secretion, and membrane permeability. The protein enzyme contains two catalytic subunits and two regulatory subunits. When there is no cAMP, the complex is inactive. When cAMP binds to the regulatory subunits, their conformation is altered, causing the dissociation of the regulatory subunits, which activates protein kinase A and allows further biological effects.
These signals then can be terminated by cAMP phosphodiesterase, which is an enzyme that degrades cAMP to 5'-AMP and inactivates protein kinase A.
=== Phosphatidylinositol signal pathway ===
In the phosphatidylinositol signal pathway, the extracellular signal molecule binds with the G-protein receptor (Gq) on the cell surface and activates phospholipase C, which is located on the plasma membrane. The lipase hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 binds with the IP3 receptor in the membrane of the smooth endoplasmic reticulum and mitochondria to open Ca2+ channels. DAG helps activate protein kinase C (PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses.
The effects of Ca2+ are also remarkable: it cooperates with DAG in activating PKC and can activate the CaM kinase pathway, in which calcium-modulated protein calmodulin (CaM) binds Ca2+, undergoes a change in conformation, and activates CaM kinase II, which has unique ability to increase its binding affinity to CaM by autophosphorylation, making CaM unavailable for the activation of other enzymes. The kinase then phosphorylates target enzymes, regulating their activities. The two signal pathways are connected together by Ca2+-CaM, which is also a regulatory subunit of adenylyl cyclase and phosphodiesterase in the cAMP signal pathway.
== Receptor regulation ==
GPCRs become desensitized when exposed to their ligand for a long period of time. There are two recognized forms of desensitization: 1) homologous desensitization, in which the activated GPCR is downregulated; and 2) heterologous desensitization, wherein the activated GPCR causes downregulation of a different GPCR. The key reaction of this downregulation is the phosphorylation of the intracellular (or cytoplasmic) receptor domain by protein kinases.
=== Phosphorylation by cAMP-dependent protein kinases ===
Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was activated by the receptor) via adenylate cyclase and cyclic AMP (cAMP). In a feedback mechanism, these activated kinases phosphorylate the receptor. The longer the receptor remains active the more kinases are activated and the more receptors are phosphorylated. In β2-adrenoceptors, this phosphorylation results in the switching of the coupling from the Gs class of G-protein to the Gi class. cAMP-dependent PKA mediated phosphorylation can cause heterologous desensitisation in receptors other than those activated.
=== Phosphorylation by GRKs ===
The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs. G-protein-coupled receptor kinases (GRKs) are key modulators of G-protein-coupled receptor (GPCR) signaling. They constitute a family of seven mammalian serine-threonine protein kinases that phosphorylate agonist-bound receptor. GRKs-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization. Activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium-sensitive proteins.
Phosphorylation of the receptor can have two consequences:
Translocation: The receptor is, along with the part of the membrane it is embedded in, brought to the inside of the cell, where it is dephosphorylated within the acidic vesicular environment and then brought back. This mechanism is used to regulate long-term exposure, for example, to a hormone, by allowing resensitisation to follow desensitisation. Alternatively, the receptor may undergo lysozomal degradation, or remain internalised, where it is thought to participate in the initiation of signalling events, the nature of which depending on the internalised vesicle's subcellular localisation.
Arrestin linking: The phosphorylated receptor can be linked to arrestin molecules that prevent it from binding (and activating) G proteins, in effect switching it off for a short period of time. This mechanism is used, for example, with rhodopsin in retina cells to compensate for exposure to bright light. In many cases, arrestin's binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β2-adrenoreceptors acts as an adaptor for binding with clathrin, and with the beta-subunit of AP2 (clathrin adaptor molecules); thus, the arrestin here acts as a scaffold assembling the components needed for clathrin-mediated endocytosis of β2-adrenoreceptors.
=== Mechanisms of GPCR signal termination ===
As mentioned above, G-proteins may terminate their own activation due to their intrinsic GTP→GDP hydrolysis capability. However, this reaction proceeds at a slow rate (≈0.02 times/sec) and, thus, it would take around 50 seconds for any single G-protein to deactivate if other factors did not come into play. Indeed, there are around 30 isoforms of RGS proteins that, when bound to Gα through their GAP domain, accelerate the hydrolysis rate to ≈30 times/sec. This 1500-fold increase in rate allows for the cell to respond to external signals with high speed, as well as spatial resolution due to limited amount of second messenger that can be generated and limited distance a G-protein can diffuse in 0.03 seconds. For the most part, the RGS proteins are promiscuous in their ability to deactivate G-proteins, while which RGS is involved in a given signaling pathway seems more determined by the tissue and GPCR involved than anything else. In addition, RGS proteins have the additional function of increasing the rate of GTP-GDP exchange at GPCRs, (i.e., as a sort of co-GEF) further contributing to the time resolution of GPCR signaling.
In addition, the GPCR may be desensitized itself. This can occur as:
a direct result of ligand occupation, wherein the change in conformation allows recruitment of GPCR-Regulating Kinases (GRKs), which go on to phosphorylate various serine/threonine residues of IL-3 and the C-terminal tail. Upon GRK phosphorylation, the GPCR's affinity for β-arrestin (β-arrestin-1/2 in most tissues) is increased, at which point β-arrestin may bind and act to both sterically hinder G-protein coupling as well as initiate the process of receptor internalization through clathrin-mediated endocytosis. Because only the liganded receptor is desensitized by this mechanism, it is called homologous desensitization
the affinity for β-arrestin may be increased in a ligand occupation and GRK-independent manner through phosphorylation of different ser/thr sites (but also of IL-3 and the C-terminal tail) by PKC and PKA. These phosphorylations are often sufficient to impair G-protein coupling on their own as well.
PKC/PKA may, instead, phosphorylate GRKs, which can also lead to GPCR phosphorylation and β-arrestin binding in an occupation-independent manner. These latter two mechanisms allow for desensitization of one GPCR due to the activities of others, or heterologous desensitization. GRKs may also have GAP domains and so may contribute to inactivation through non-kinase mechanisms as well. A combination of these mechanisms may also occur.
Once β-arrestin is bound to a GPCR, it undergoes a conformational change allowing it to serve as a scaffolding protein for an adaptor complex termed AP-2, which in turn recruits another protein called clathrin. If enough receptors in the local area recruit clathrin in this manner, they aggregate and the membrane buds inwardly as a result of interactions between the molecules of clathrin, in a process called opsonization. Once the pit has been pinched off the plasma membrane due to the actions of two other proteins called amphiphysin and dynamin, it is now an endocytic vesicle. At this point, the adapter molecules and clathrin have dissociated, and the receptor is either trafficked back to the plasma membrane or targeted to lysosomes for degradation.
At any point in this process, the β-arrestins may also recruit other proteins—such as the non-receptor tyrosine kinase (nRTK), c-SRC—which may activate ERK1/2, or other mitogen-activated protein kinase (MAPK) signaling through, for example, phosphorylation of the small GTPase, Ras, or recruit the proteins of the ERK cascade directly (i.e., Raf-1, MEK, ERK-1/2) at which point signaling is initiated due to their close proximity to one another. Another target of c-SRC are the dynamin molecules involved in endocytosis. Dynamins polymerize around the neck of an incoming vesicle, and their phosphorylation by c-SRC provides the energy necessary for the conformational change allowing the final "pinching off" from the membrane.
=== GPCR cellular regulation ===
Receptor desensitization is mediated through a combination phosphorylation, β-arr binding, and endocytosis as described above. Downregulation occurs when endocytosed receptor is embedded in an endosome that is trafficked to merge with an organelle called a lysosome. Because lysosomal membranes are rich in proton pumps, their interiors have low pH (≈4.8 vs. the pH≈7.2 cytosol), which acts to denature the GPCRs. In addition, lysosomes contain many degradative enzymes, including proteases, which can function only at such low pH, and so the peptide bonds joining the residues of the GPCR together may be cleaved. Whether or not a given receptor is trafficked to a lysosome, detained in endosomes, or trafficked back to the plasma membrane depends on a variety of factors, including receptor type and magnitude of the signal.
GPCR regulation is additionally mediated by gene transcription factors. These factors can increase or decrease gene transcription and thus increase or decrease the generation of new receptors (up- or down-regulation) that travel to the cell membrane.
== Receptor oligomerization ==
G-protein-coupled receptor oligomerisation is a widespread phenomenon. One of the best-studied examples is the metabotropic GABAB receptor. This so-called constitutive receptor is formed by heterodimerization of GABABR1 and GABABR2 subunits. Expression of the GABABR1 without the GABABR2 in heterologous systems leads to retention of the subunit in the endoplasmic reticulum. Expression of the GABABR2 subunit alone, meanwhile, leads to surface expression of the subunit, although with no functional activity (i.e., the receptor does not bind agonist and cannot initiate a response following exposure to agonist). Expression of the two subunits together leads to plasma membrane expression of functional receptor. It has been shown that GABABR2 binding to GABABR1 causes masking of a retention signal of functional receptors.
== Origin and diversification of the superfamily ==
Signal transduction mediated by the superfamily of GPCRs dates back to the origin of multicellularity. Mammalian-like GPCRs are found in fungi, and have been classified according to the GRAFS classification system based on GPCR fingerprints. Identification of the superfamily members across the eukaryotic domain, and comparison of the family-specific motifs, have shown that the superfamily of GPCRs have a common origin. Characteristic motifs indicate that three of the five GRAFS families, Rhodopsin, Adhesion, and Frizzled, evolved from the Dictyostelium discoideum cAMP receptors before the split of opisthokonts. Later, the Secretin family evolved from the Adhesion GPCR receptor family before the split of nematodes. Insect GPCRs appear to be in their own group and Taste2 is identified as descending from Rhodopsin. Note that the Secretin/Adhesion split is based on presumed function rather than signature, as the classical Class B (7tm_2, Pfam PF00002) is used to identify both in the studies.
== See also ==
G protein-coupled receptors database
List of MeSH codes (D12.776)
Metabotropic receptor
Orphan receptor
Pepducins, a class of drug candidates targeted at GPCRs
Receptor activated solely by a synthetic ligand, a technique for control of cell signaling through synthetic GPCRs
TOG superfamily
== References ==
== Further reading ==
Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (April 2003). "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America. 100 (8): 4903–8. Bibcode:2003PNAS..100.4903V. doi:10.1073/pnas.0230374100. PMC 153653. PMID 12679517.
"GPCR Reference Library". Retrieved 11 August 2008. Reference for molecular and mathematical models for the initial receptor response
"The Nobel Prize in Chemistry 2012" (PDF). Archived (PDF) from the original on 18 October 2012. Retrieved 10 October 2012.
== External links ==
G-protein-coupled+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
GPCR Cell Line Archived 3 April 2015 at the Wayback Machine
"IUPHAR/BPS Guide to PHARMACOLOGY Database (GPCRs)". IUPHAR Database. University of Edinburgh / International Union of Basic and Clinical Pharmacology. Retrieved 6 February 2019.
"GPCRdb". Data, diagrams and web tools for G protein-coupled receptors (GPCRs).; Munk C, Isberg V, Mordalski S, Harpsøe K, Rataj K, Hauser AS, et al. (July 2016). "GPCRdb: the G protein-coupled receptor database - an introduction". British Journal of Pharmacology. 173 (14): 2195–207. doi:10.1111/bph.13509. PMC 4919580. PMID 27155948.
"G Protein-Coupled Receptors on the NET". Archived from the original on 23 July 2011. Retrieved 10 November 2010. a classification of GPCRs
"PSI GPCR Network Center". Archived from the original on 25 July 2013. Retrieved 11 July 2013. a Protein Structure Initiative:Biology Network Center aimed at determining the 3D structures of representative GPCR family proteins
GPCR-HGmod Archived 1 February 2016 at the Wayback Machine, a database of 3D structural models of all human G-protein coupled receptors, built by the GPCR-I-TASSER pipeline Zhang J, Yang J, Jang R, Zhang Y (August 2015). "GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome". Structure. 23 (8): 1538–1549. doi:10.1016/j.str.2015.06.007. PMC 4526412. PMID 26190572. | Wikipedia/G_protein_coupled_receptor |
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a significant fraction of the proteins encoded in an organism's genome. Proteins that cross the membrane are surrounded by annular lipids, which are defined as lipids that are in direct contact with a membrane protein. Such proteins can only be separated from the membranes by using detergents, nonpolar solvents, or sometimes denaturing agents.
Proteins that adhere only temporarily to cellular membranes are known as peripheral membrane proteins. These proteins can either associate with integral membrane proteins, or independently insert in the lipid bilayer in several ways.
== Structure ==
Three-dimensional structures of ~160 different integral membrane proteins have been determined at atomic resolution by X-ray crystallography or nuclear magnetic resonance spectroscopy. They are challenging subjects for study owing to the difficulties associated with extraction and crystallization. In addition, structures of many water-soluble protein domains of IMPs are available in the Protein Data Bank. Their membrane-anchoring α-helices have been removed to facilitate the extraction and crystallization. Search integral membrane proteins in the PDB (based on gene ontology classification)
IMPs can be divided into two groups:
Integral polytopic proteins (Transmembrane proteins)
Integral monotopic proteins
=== Integral polytopic protein ===
The most common type of IMP is the transmembrane protein, which spans the entire biological membrane. Single-pass membrane proteins cross the membrane only once, while multi-pass membrane proteins weave in and out, crossing the membrane several times. Single pass membrane proteins can be categorized as Type I, which are positioned such that their carboxyl-terminus is towards the cytosol, or Type II, which have their amino-terminus towards the cytosol. Type III proteins have multiple transmembrane domains in a single polypeptide, while type IV consists of several different polypeptides assembled together in a channel through the membrane. Type V proteins are anchored to the lipid bilayer through covalently linked lipids. Finally Type VI proteins have both transmembrane domains and lipid anchors.
=== Integral monotopic proteins ===
Integral monotopic proteins are permanently attached to the cell membrane from one side.
Three-dimensional structures of the following integral monotopic proteins have been determined:
prostaglandin H2 syntheses 1 and 2 (cyclooxygenases)
lanosterol synthase and squalene-hopene cyclase
microsomal prostaglandin E synthase
carnitine O-palmitoyltransferase 2
Phosphoglycosyl transferase C
There are also structures of integral monotopic domains of transmembrane proteins:
monoamine oxidases A and B
fatty acid amide hydrolase
mammalian cytochrome P450 oxidases
corticosteroid 11-beta-dehydrogenases
=== Extraction ===
Many challenges facing the study of integral membrane proteins are attributed to the extraction of those proteins from the phospholipid bilayer. Since integral proteins span the width of the phospholipid bilayer, their extraction involves disrupting the phospholipids surrounding them, without causing any damage that would interrupt the function or structure of the proteins. Several successful methods are available for performing the extraction including the uses of "detergents, low ionic salt (salting out), shearing force, and rapid pressure change".
=== Determination of protein structure ===
The Protein Structure Initiative (PSI), funded by the U.S. National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health (NIH), has among its aim to determine three-dimensional protein structures and to develop techniques for use in structural biology, including for membrane proteins. Homology modeling can be used to construct an atomic-resolution model of the "target" integral protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous protein. This procedure has been extensively used for ligand-G protein–coupled receptors (GPCR) and their complexes.
== Function ==
IMPs include transporters, linkers, channels, receptors, enzymes, structural membrane-anchoring domains, proteins involved in accumulation and transduction of energy, and proteins responsible for cell adhesion. Classification of transporters can be found in Transporter Classification Database.
As an example of the relationship between the IMP (in this case the bacterial phototrapping pigment, bacteriorhodopsin) and the membrane formed by the phospholipid bilayer is illustrated below. In this case the integral membrane protein spans the phospholipid bilayer seven times. The part of the protein that is embedded in the hydrophobic regions of the bilayer are alpha helical and composed of predominantly hydrophobic amino acids. The C terminal end of the protein is in the cytosol while the N terminal region is in the outside of the cell. A membrane that contains this particular protein is able to function in photosynthesis.
== Examples ==
Examples of integral membrane proteins:
Insulin receptor
Some types of cell adhesion proteins or cell adhesion molecules (CAMs) such as integrins, cadherins, NCAMs, or selectins
Some types of receptor proteins
Glycophorin
Rhodopsin
Band 3
CD36
Glucose Permease
Ion channels and Gates
Gap junction Proteins
G protein coupled receptors (e.g., Beta-adrenergic receptor)
Seipin
Photosystem I
== See also ==
Membrane protein
Transmembrane protein
Peripheral membrane protein
Annular lipid shell
Hydrophilicity plot
Inner nuclear membrane protein
== References == | Wikipedia/Integral_monotopic_protein |
Within evolutionary biology, signalling theory is a body of theoretical work examining communication between individuals, both within species and across species. The central question is how organisms with conflicting interests, such as in sexual selection, are expected to provide honest signals rather than deceive or cheat, given that the passing on of pleiotropic traits is subject to natural selection, which aims to minimize associated costs without assuming any conscious intent. Mathematical models describe how signalling can contribute to an evolutionarily stable strategy.
Signals are given in contexts such as mate selection by females, which subjects the advertising males' signals to selective pressure. Signals thus evolve because they modify the behaviour of the receiver to benefit the signaller. Signals may be honest, conveying information which usefully increases the fitness of the receiver, or dishonest. An individual can cheat by giving a dishonest signal, which might briefly benefit that signaller, at the risk of undermining the signalling system for the whole population.
The question of whether the selection of signals works at the level of the individual organism or gene, or at the level of the group, has been debated by biologists such as Richard Dawkins, arguing that individuals evolve to signal and to receive signals better, including resisting manipulation. Amotz Zahavi suggested that cheating could be controlled by the handicap principle, where the best horse in a handicap race is the one carrying the largest handicap weight. According to Zahavi's theory, signallers such as male peacocks have "tails" that are genuinely handicaps, being costly to produce. The system is evolutionarily stable as the large showy tails are honest signals. Biologists have attempted to verify the handicap principle, but with inconsistent results. The mathematical biologist Ronald Fisher analysed the contribution that having two copies of each gene (diploidy) would make to honest signalling, demonstrating that a runaway effect could occur in sexual selection. The evolutionary equilibrium depends sensitively on the balance of costs and benefits.
The same mechanisms can be expected in humans, where researchers have studied behaviours including risk-taking by young men, hunting of large game animals, and costly religious rituals, finding that these appear to qualify as costly honest signals.
== Sexual selection ==
When animals choose mating partners, traits such as signalling are subject to evolutionary pressure. For example, the male gray tree frog, Dryophytes versicolor, produces a call to attract females. Once a female chooses a mate, this selects for a specific style of male calling, thus propagating a specific signalling ability. The signal can be the call itself, the intensity of a call, its variation style, its repetition rate, and so on. Various hypotheses seek to explain why females would select for one call over the other. The sensory exploitation hypothesis proposes that pre-existing preferences in female receivers can drive the evolution of signal innovation in male senders, in a similar way to the hidden preference hypothesis which proposes that successful calls are better able to match some 'hidden preference' in the female. Signallers have sometimes evolved multiple sexual ornaments, and receivers have sometimes evolved multiple trait preferences.
== Honest signals ==
In biology, signals are traits, including structures and behaviours, that have evolved specifically because they change the behaviour of receivers in ways that benefit the signaller. Traits or actions that benefit the receiver exclusively are called "cues". For example, when an alert bird deliberately gives a warning call to a stalking predator and the predator gives up the hunt, the sound is a "signal". But when a foraging bird inadvertently makes a rustling sound in the leaves that attracts predators and increases the risk of predation, the sound is not a signal, but a cue.
Signalling systems are shaped by mutual interests between signallers and receivers. An alert bird such as a Eurasian jay warning off a stalking predator is communicating something useful to the predator: that it has been detected by the prey; it might as well quit wasting its time stalking this alerted prey, which it is unlikely to catch. When the predator gives up, the signaller can get back to other tasks such as feeding. Once the stalking predator is detected, the signalling prey and receiving predator thus have a mutual interest in terminating the hunt.
Within species, mutual interests increase with kinship. Kinship is central to models of signalling between relatives, for instance when broods of nestling birds beg and compete for food from their parents.
The term honesty in animal communication is controversial because in non-technical usage it implies intent, to discriminate deception from honesty in human interactions. However, biologists use the phrase "honest signals" in a direct, statistical sense. Biological signals, like warning calls or resplendent tail feathers, are honest if they reliably convey useful information to the receiver. That is, the signal trait tells the receiver about an otherwise unobservable factor. Honest biological signals do not need to be perfectly informative, reducing uncertainty to zero; all they need to be useful is to be correct "on average", so that some behavioural response to the signal is advantageous, statistically, compared to the behaviour that would occur in absence of the signal. Ultimately the value of the signalled information depends on the extent to which it allows the receiver to increase its fitness.
One type of honest signal is the signalling of quality in sexually reproducing animals. In sexually reproducing animals one sex is generally the 'choosing sex' (often females) and the other the 'advertising sex' (often males). The choosing sex achieves the highest fitness by choosing the partner of the highest (genetic) quality. This quality cannot be observed directly, so the advertising sex can evolve a signal, which advertises its quality. Examples of these signals include the tail of a peacock and the colouration of male sticklebacks. Such signals only work, i.e. are reliable, if the signal is honest. The link between the quality of the advertising sex and the signal may depend on environmental stressors, with honesty increasing in more challenging environments.
Another type of honest signal is the aposematic warning signal, generally visual, given by poisonous or dangerous animals such as wasps, poison dart frogs, and pufferfish. Warning signals are honest indications of noxious prey, because conspicuousness evolves in tandem with noxiousness (a conspicuous, non-noxious organism gets eaten). Thus, the brighter and more conspicuous the organism, the more toxic it usually is. The most common and effective colours are red, yellow, black and white.
The mathematical biologist John Maynard Smith discusses whether honest signalling must always be costly. He notes that it had been shown that "in some circumstances" a signal is reliable only if it is costly. He states that it had been assumed that parameters such as pay-offs and signalling costs were constant, but that this might be unrealistic. He states that with some restrictions, signals can be cost-free, reliable, and evolutionarily stable. However, if costs and benefits "vary uniformly over the whole range" then indeed honest signals have to be costly.
== Dishonest signals ==
Because there are both mutual and conflicting interests in most animal signalling systems, a central problem in signalling theory is dishonesty or cheating. For example, if foraging birds are safer when they give a warning call, cheats could give false alarms at random, just in case a predator is nearby. But too much cheating could cause the signalling system to collapse. Every dishonest signal weakens the integrity of the signalling system, and so reduces the fitness of the group. An example of dishonest signalling comes from Fiddler crabs such as Austruca mjoebergi, which have been shown to bluff (no conscious intention being implied) about their fighting ability. When a claw is lost, a crab occasionally regrows a weaker claw that nevertheless intimidates crabs with smaller but stronger claws. The proportion of dishonest signals is low enough for it not to be worthwhile for crabs to test the honesty of every signal through combat.
Richard Dawkins and John Krebs in 1978 considered whether individuals of the same species would act as if attempting to deceive each other. They applied a "selfish gene" view of evolution to animals' threat displays to see if it would be in their genes' interests to give dishonest signals. They criticised previous ethologists, such as Nikolaas Tinbergen and Desmond Morris, for suggesting that such displays were "for the good of the species". They argued that such communication ought to be viewed as an evolutionary arms race in which signallers evolve to become better at manipulating receivers, while receivers evolve to become more resistant to manipulation. The game theoretical model of the war of attrition similarly suggests that threat displays ought not to convey any reliable information about intentions.
Deceptive signals can be used both within and between species. Perhaps the best-known example of inter-species deception is mimicry: when individuals of one species mimic the appearance or behaviour of individuals of another species. A variety of mimicry types exist, including Batesian, Müllerian, host mimicry and "aggressive" mimicry. A very frequent type is ant mimicry. Deception within species can be bluffing (during contest) or sexual mimicry where males or females mimic the patterns and behaviour of the opposite sex. A famous example is the bluegill sunfish where mimic males look like and behave like females to sneak into the guarded nests of territorial males in order to fertilize some of the eggs.
== Handicap principle ==
In 1975, Amotz Zahavi proposed a verbal model for how signal costs could constrain cheating and stabilize an "honest" correlation between observed signals and unobservable qualities, based on an analogy to sports handicapping systems. He called this idea the handicap principle. The purpose of a sports handicapping system is to reduce disparities in performance, making the contest more competitive. In a handicap race, intrinsically faster horses are given heavier weights to carry under their saddles. Similarly, in amateur golf, better golfers have fewer strokes subtracted from their raw scores. This creates correlations between the handicap and unhandicapped performance, if the handicaps work as they are supposed to, between the handicap imposed and the corresponding horse's handicapped performance. If nothing was known about two race horses or two amateur golfers except their handicaps, an observer could infer who is most likely to win: the horse with the bigger weight handicap, and the golfer with the smaller stroke handicap. By analogy, if peacock 'tails' (large tail covert feathers) act as a handicapping system, and a peahen knew nothing about two peacocks except the sizes of their tails, she could "infer" that the peacock with the bigger tail has greater unobservable intrinsic quality. Display costs can include extrinsic social costs, in the form of testing and punishment by rivals, as well as intrinsic production costs. Another example given in textbooks is the extinct Irish elk, Megaloceros giganteus. The male Irish elk's enormous antlers could perhaps have evolved as displays of ability to overcome handicap, though biologists point out that if the handicap is inherited, its genes ought to be selected against.
The essential idea here is intuitive and probably qualifies as folk wisdom. It was articulated by Kurt Vonnegut in his 1961 short story Harrison Bergeron. In Vonnegut's futuristic dystopia, the Handicapper General uses a variety of handicapping mechanisms to reduce inequalities in performance. A spectator at a ballet comments: "it was easy to see that she was the strongest and most graceful of all dancers, for her handicap bags were as big as those worn by two hundred pound men." Zahavi interpreted this analogy to mean that higher quality peacocks with bigger tails are signalling their ability to "waste" more of some resource by trading it off for a bigger tail. This resonates with Thorstein Veblen's idea that conspicuous consumption and extravagant status symbols can signal wealth.
Zahavi's conclusions rest on his verbal interpretation of a metaphor, and initially the handicap principle was not well received by evolutionary biologists. However, in 1984, Nur and Hasson used life history theory to show how differences in signalling costs, in the form of survival-reproduction tradeoffs, could stabilize a signalling system roughly as Zahavi imagined. Genetic models also suggested this was possible. In 1990 Alan Grafen showed that a handicap-like signalling system was evolutionarily stable if higher quality signallers paid lower marginal survival costs for their signals.
In 1982, W. D. Hamilton proposed a specific but widely applicable handicap mechanism, parasite-mediated sexual selection. He argued that in the never-ending co-evolutionary race between hosts and their parasites, sexually selected signals indicate health. This idea was tested in 1994 in barn swallows, a species where males have long tail streamers. Møller found that the males with longer tails, and their offspring, did have fewer bloodsucking mites, whereas fostered young did not. The effect was therefore genetic, confirming Hamilton's theory.
Another example is Lozano's hypothesis that carotenoids have dual but mutually incompatible roles in immune function and signalling. Given that animals cannot synthesize carotenoids de novo, these must be obtained from food. The hypothesis states that animals with carotenoid-depended sexual signals are demonstrating their ability to "waste" carotenoids on sexual signals at the expense of their immune system.
The handicap principle has proven hard to test empirically, partly because of inconsistent interpretations of Zahavi's metaphor and Grafen's marginal fitness model, and partly because of conflicting empirical results: in some studies individuals with bigger signals seem to pay higher costs, in other studies they seem to be paying lower costs. A possible explanation for the inconsistent empirical results is given in a series of papers by Getty, who shows that Grafen's proof of the handicap principle is based on the critical simplifying assumption that signallers trade off costs for benefits in an additive fashion, the way humans invest money to increase income in the same currency. But the assumption that costs and benefits trade off in an additive fashion is true only on a logarithmic scale; for the survival cost – reproduction benefit tradeoff is assumed to mediate the evolution of sexually selected signals. Fitness depends on producing offspring, which is a multiplicative function of reproductive success given an individual is still alive times the probability of still being alive, given investment in signals.
Later models have shown that the popularity of handicap principle relies on the critical misinterpretation of Grafen's model by Grafen himself. Contrary to his claims, his model is not a model of handicap signalling. Grafen's key equations show the necessity of marginal cost and differential marginal cost, nowhere in his paper was Grafen able to show the necessity of wasteful equilibrium cost (a.k.a. handicap). Grafen's model is a model of condition dependent signalling that builds on a traditional life-history trade-off between reproduction and survival. In general, later models have shown that the key condition of honest signalling is the existence of such condition-dependent trade-off and that the cost of signals can be anything at the equilibrium for honest individuals, including zero or even negative. The reason is that deception is prevented by the potential cost of cheating and not by the cost paid by the honest individuals. This potential cost of cheating (marginal cost) has to be larger than the potential (marginal) benefits for potential cheaters. In turn this implies that the honest peacock or deer need not be wasteful, it will be efficient. It is the potential cheater that needs to be less efficient. Signal selection is not a selection for waste, as claimed by Zahavi, it is guided by the same mechanism - natural selection - as any other trait in nature.
== Costly signalling and Fisherian diploid dynamics ==
The effort to discover how costs can constrain an "honest" correlation between observable signals and unobservable qualities within signallers is built on strategic models of signalling games, with many simplifying assumptions. These models are most often applied to sexually selected signalling in diploid animals, but they rarely incorporate a fact about diploid sexual reproduction noted by the mathematical biologist Ronald Fisher in the early 20th century: if there are "preference genes" correlated with choosiness in females as well as "signal genes" correlated with display traits in males, choosier females should tend to mate with showier males. Over generations, showier sons should also carry genes associated with choosier daughters, and choosier daughters should also carry genes associated with showier sons. This can cause the evolutionary dynamic known as Fisherian runaway, in which males become ever showier. Russell Lande explored this with a quantitative genetic model, showing that Fisherian diploid dynamics are sensitive to signalling and search costs. Other models incorporate both costly signalling and Fisherian runaway. These models show that if fitness depends on both survival and reproduction, having sexy sons and choosy daughters (in the stereotypical model) can be adaptive, increasing fitness just as much as having healthy sons and daughters.
== Models of signalling interactions ==
Perhaps the most popular tool to investigate signalling interactions is game theory. A typical model investigates an interaction between a signaller and a receiver. Games can be symmetrical or asymmetric. There can be several types of asymmetries including asymmetry in resources or asymmetry of information. In many asymmetric games the receiver is in a possession of a resource that the signaller wants to get (resource asymmetry). Signallers can be a of different types, the type of any given signaller is assumed to be hidden (information asymmetry). Asymmetric games are frequently used to model mate choice (sexual selection) or parent-offspring interactions. Asymmetric games are also used to model interspecific interactions such as predator-prey, host-parasite or plant-pollinator signalling. Symmetric games can be used to model competition for resources, such as animals fighting for food or for a territory.
== Human honest signals ==
Human behaviour may also provide examples of costly signals. In general, these signals provide information about a person's phenotypic quality or cooperative tendencies. Evidence for costly signalling has been found in many areas of human interaction including risk-taking, hunting, and religion.
=== Costly signalling in hunting ===
Large game hunting has been studied extensively as a signal of men's willingness to take physical risks, as well as showcase strength and coordination. Costly signalling theory is a useful tool for understanding food sharing among hunter gatherers because it can be applied to situations in which delayed reciprocity is not a viable explanation. Instances that are particularly inconsistent with the delayed reciprocity hypothesis are those in which a hunter shares his kill indiscriminately with all members of a large group. In these situations, the individuals sharing meat have no control over whether or not their generosity will be reciprocated, and free riding becomes an attractive strategy for those receiving meat. Free riders are people who reap the benefits of group-living without contributing to its maintenance. Costly signalling theory can fill some of the gaps left by the delayed reciprocity hypothesis. Hawkes has suggested that men target large game and publicly share meat to draw social attention or to show off. Such display and the resulting favorable attention can improve a hunter's reputation by providing information about his phenotypic quality. High quality signallers are more successful in acquiring mates and allies. Thus, costly signalling theory can explain apparently wasteful and altruistic behaviour.
In order to be effective, costly signals must fulfill specific criteria. Firstly, signallers must incur different levels of cost and benefit for signalling behaviour. Secondly, costs and benefits must reflect the signallers' phenotypic quality. Thirdly, the information provided by a signal should be directed at and accessible to an audience. A receiver can be anyone who stands to benefit from information the signaller is sending, such as potential mates, allies, or competitors. Honesty is guaranteed when only individuals of high quality can pay the (high) costs of signalling. Hence, costly signals make it impossible for low-quality individuals to fake a signal and fool a receiver.
Bliege Bird et al. observed turtle hunting and spear fishing patterns in a Meriam community in the Torres Strait of Australia, publishing their findings in 2001. Here, only some Meriam men were able to accumulate high caloric gains for the amount of time spent turtle hunting or spear fishing (reaching a threshold measured in kcal/h). Since a daily catch of fish is carried home by hand and turtles are frequently served at large feasts, members of the community know which men most reliably brought them turtle meat and fish. Thus, turtle hunting qualifies as a costly signal. Furthermore, turtle hunting and spear fishing are actually less productive (in kcal/h) than foraging for shellfish, where success depends only on the amount of time dedicated to searching, so shellfish foraging is a poor signal of skill or strength. This suggests that energetic gains are not the primary reason men take part in turtle hunting and spear fishing. A follow-up study found that successful Meriam hunters do experience greater social benefits and reproductive success than less skilled hunters.
The Hadza people of Tanzania also share food, possibly to gain in reputation. Hunters cannot be sharing meat mainly to provision their families or to gain reciprocal benefits, as teenage boys often give away their meat even though they do not yet have wives or children, so costly signalling of their qualities is the likely explanation. These qualities include good eyesight, coordination, strength, knowledge, endurance, or bravery. Hadza hunters more often pair with highly fertile, hard-working wives than non-hunters. A woman benefits from mating with a man who possesses such qualities as her children will most likely inherit qualities that increase fitness and survivorship. She may also benefit from her husband's high social status. Thus, hunting is an honest and costly signal of phenotypic quality. Frank W. Marlowe's The Hadza: Hunter-Gatherers of Tanzania showed that this data confirms that this is also true within the Hadza, based on the documentation on the !Kung, in Megan Biesele's book on !Kung folklore, Women Like Meat.
Among the men of Ifaluk atoll, costly signalling theory can also explain why men torch fish. Torch fishing is a ritualized method of fishing on Ifaluk whereby men use torches made from dried coconut fronds to catch large dog-toothed tuna. Preparation for torch fishing requires significant time investments and involves a great deal of organization. Due to the time and energetic costs of preparation, torch fishing results in net caloric losses for fishers. Therefore, torch fishing is a handicap that serves to signal men's productivity. Torch fishing is the most advertised fishing occupation on Ifaluk. Women and others usually spend time observing the canoes as they sail beyond the reef. Also, local rituals help to broadcast information about which fishers are successful and enhance fishers' reputations during the torch fishing season. Several ritual behaviors and dietary constraints clearly distinguish torch fishers from other men. First, males are only permitted to torch fish if they participate on the first day of the fishing season. The community is well informed as to who participates on this day, and can easily identify the torch fishers. Second, torch fishers receive all of their meals at the canoe house and are prohibited from eating certain foods. People frequently discuss the qualities of torch fishermen. On Ifaluk, women claim that they are looking for hard-working mates. With the distinct sexual division of labor on Ifaluk, industriousness is a highly valued characteristic in males. Torch fishing thus provides women with reliable information on the work ethic of prospective mates, which makes it an honest costly signal.
In many human cases, a strong reputation built through costly signalling enhances a man's social status over the statuses of men who signal less successfully. Among northern Kalahari foraging groups, traditional hunters usually capture a maximum of two or three antelopes per year. It was said of a particularly successful hunter:
"It was said of him that he never returned from a hunt without having killed at least a wildebeest, if not something larger. Hence the people connected with him ate a great deal of meat and his popularity grew."
Although this hunter was sharing meat, he was not doing so in the framework of reciprocity. The general model of costly signalling is not reciprocal; rather, individuals who share acquire more mates and allies. Costly signalling applies to situations in Kalahari foraging groups where giving often goes to recipients who have little to offer in return. A young hunter is motivated to impress community members with daughters so that he can obtain his first wife. Older hunters may wish to attract women interested in an extramarital relationship, or to be a co-wife. In these northern Kalahari groups, the killing of a large animal indicates a man who has mastered the art of hunting and can support a family. Many women seek a man who is a good hunter, has an agreeable character, is generous, and has advantageous social ties. Since hunting ability is a prerequisite for marriage, men who are good hunters enter the marriage market earliest. Costly signalling theory explains seemingly wasteful foraging displays.
=== Physical risk ===
Costly signalling can be applied to situations involving physical strain and risk of physical injury or death. Research on physical risk-taking is important because information regarding why people, especially young men, take part in high risk activities can help in the development of prevention programs. Reckless driving is a lethal problem among young men in western societies. A male who takes a physical risk is sending the message that he has enough strength and skill to survive extremely dangerous activities. This signal is directed at peers and potential mates. When those peers are criminals or gang members, sociologists Diego Gambetta and James Densley find that risk-taking signals can help expedite acceptance into the group.
In a study of risk-taking, some types of risk, such as physical or heroic risk for others' benefit, are viewed more favorably than other types of risk, such as taking drugs. Males and females valued different degrees of heroic risk for mates and same-sex friends. Males valued heroic risk-taking by male friends, but preferred less of it in female mates. Females valued heroic risk-taking in male mates and less of it in female friends. Females may be attracted to males inclined to physically defend them and their children. Males may prefer heroic risk-taking by male friends as they could be good allies.
In western societies, voluntary blood donation is a common, yet less extreme, form of risk-taking. Costs associated with these donations include pain and risk of infection. If blood donation is an opportunity to send costly signals, then donors will be perceived by others as generous and physically healthy. In a survey, both donors and non-donors attributed health, generosity, and ability to operate in stressful situations to blood donors.
=== Religion ===
Costly religious rituals such as genital modification, food and water deprivation, and snake handling look paradoxical in evolutionary terms. Devout religious beliefs wherein such traditions are practiced appear maladaptive. Religion may have arisen to increase and maintain intragroup cooperation. Cooperation leads to altruistic behaviour, and costly signalling could explain this. All religions may involve costly and elaborate rituals, performed publicly, to demonstrate loyalty to the religious group. In this way, group members increase their allegiance to the group by signalling their investment in group interests. However, as group size increases among humans, the threat of free riders grows. Costly signalling theory accounts for this by proposing that these religious rituals are costly enough to deter free riders.
Irons proposed that costly signalling theory could explain costly religious behaviour. He argued that hard-to-fake religious displays enhanced trust and solidarity in a community, producing emotional and economic benefits. He showed that display signals among the Yomut Turkmen of northern Iran helped to secure trade agreements. These "ostentatious" displays signalled commitment to Islam to strangers and group members. Sosis demonstrated that people in religious communities are four times more likely to live longer than their secular counterparts, and that these longer lifespans were positively correlated with the number of costly requirements demanded from religious community members. However, confounding variables may not have been excluded. Wood found that religion offers a subjective feeling of well-being within a community, where costly signalling protects against free riders and helps to build self-control among committed members. Iannaccone studied the effects of costly signals on religious communities. In a self-reported survey, as the strictness of a church increased, the attendance and contributions to that church increased proportionally. In effect, people were more willing to participate in a church that has more stringent demands on its members. Despite this observation, costly donations and acts conducted in a religious context does not itself establish that membership in these clubs is actually worth the entry costs imposed.
Despite the experimental support for this hypothesis, it remains controversial. A common critique is that devoutness is easy to fake, such as simply by attending a religious service. However, the hypothesis predicts that people are more likely to join and contribute to a religious group when its rituals are costly. Another critique specifically asks: why religion? There is no evolutionary advantage to evolving religion over other signals of commitment such as nationality, as Irons admits. However, the reinforcement of religious rites as well as the intrinsic reward and punishment system found in religion makes it an ideal candidate for increasing intragroup cooperation. Finally, there is insufficient evidence for increase in fitness as a result of religious cooperation. However, Sosis argues for benefits from religion itself, such as increased longevity, improved health, assistance during crises, and greater psychological well-being, although both the supposed benefits from religion and the costly-signaling mechanism have been contested.
=== Language ===
Some scholars view the emergence of language as the consequence of some kind of social transformation that, by generating unprecedented levels of public trust, liberated a genetic potential for linguistic creativity that had previously lain dormant. "Ritual/speech coevolution theory" views rituals as costly signals that ensures honesty and reliability of language communication. Scholars in this intellectual camp argue that even chimpanzees and bonobos have latent symbolic capacities that they rarely—if ever—use in the wild. Objecting to the sudden mutation idea, these authors state that even if a chance mutation were to install a language organ in an evolving bipedal primate, it would be adaptively useless. A very specific social structure—one capable of upholding unusually high levels of public accountability and trust—must have evolved before or concurrently with language to make reliance on "cheap signals" (words) an evolutionarily stable strategy.
== See also ==
Alarm signal
Conspicuous consumption
Dramaturgy (sociology)
Game theory
Green-beard effect
Knowledge falsification
Origin of language
Signalling (economics)
Virtue signalling
Zoosemiotics
== Notes ==
== References ==
== Sources ==
=== Further reading ===
Zahavi, Amotz (1977). "The cost of honesty (Further remarks on the handicap principle)". Journal of Theoretical Biology. 67 (3): 603–605. Bibcode:1977JThBi..67..603Z. doi:10.1016/0022-5193(77)90061-3. PMID 904334.
Zahavi, Amotz (1977). "The Testing of the Bond". Animal Behaviour. 25: 246–247. doi:10.1016/0003-3472(77)90089-6. S2CID 53197593.
== External links ==
Animal behavior online: Deceit | Wikipedia/Signalling_theory |
Helicos BioSciences Corporation was a publicly traded life science company headquartered in Cambridge, Massachusetts focused on genetic analysis technologies for the research, drug discovery and diagnostic markets. The firm's Helicos Genetic Analysis Platform was the first DNA-sequencing instrument to operate by imaging individual DNA molecules. In May 2010, the company announced a 50% layoff and a re-focusing on molecular diagnostics. After long financial troubles, in November 2010, Helicos was delisted from NASDAQ.
Helicos was co-founded in 2003 by life science entrepreneur Stanley Lapidus, Stephen Quake, and Noubar Afeyan with investments from Atlas Venture, Flagship Ventures, Highland Capital Partners, MPM Capital, and Versant Ventures.
Helicos's technology images the extension of individual DNA molecules using a defined primer and individual fluorescently labeled nucleotides, which contain a "Virtual Terminator" preventing incorporation of multiple nucleotides per cycle. The "Virtual Terminator" technology was developed by Dr. Suhaib Siddiqi, while at Helicos Biosciences.
In the August 2009 issue of Nature Biotechnology, Dr. Stephen Quake, a professor of bioengineering at Stanford University and a co-founder of Helicos BioSciences, sequenced his own genome, using Single Molecule Sequencing for under $50,000 in reagents.
On November 15, 2012, Helicos BioSciences filed for Chapter 11 bankruptcy.
The patents that Helicos had licensed from Caltech (where Quake was when he made the underlying inventions) were subsequently licensed to Direct Genomics, founded by Jiankui He, a former post-doc in Quake's lab who gained notoriety in November 2018 when he created the first germline genome-edited babies.
== See also ==
Helicos single molecule fluorescent sequencing
Pharmacogenomics
Genetic counseling
Genomics
== References ==
== External links ==
Helicos BioSciences Corp. firm website (Now defunct after Bankruptcy) | Wikipedia/Helicos_Biosciences |
A DNA sequencer is a scientific instrument used to automate the DNA sequencing process. Given a sample of DNA, a DNA sequencer is used to determine the order of the four bases: G (guanine), C (cytosine), A (adenine) and T (thymine). This is then reported as a text string, called a read. Some DNA sequencers can be also considered optical instruments as they analyze light signals originating from fluorochromes attached to nucleotides.
The first automated DNA sequencer, invented by Lloyd M. Smith, was introduced by Applied Biosystems in 1987. It used the Sanger sequencing method, a technology which formed the basis of the "first generation" of DNA sequencers and enabled the completion of the human genome project in 2001. This first generation of DNA sequencers are essentially automated electrophoresis systems that detect the migration of labelled DNA fragments. Therefore, these sequencers can also be used in the genotyping of genetic markers where only the length of a DNA fragment(s) needs to be determined (e.g. microsatellites, AFLPs).
The Human Genome Project spurred the development of cheaper, high throughput and more accurate platforms known as Next Generation Sequencers (NGS) to sequence the human genome. These include the 454, SOLiD and Illumina DNA sequencing platforms. Next generation sequencing machines have increased the rate of DNA sequencing substantially, as compared with the previous Sanger methods. DNA samples can be prepared automatically in as little as 90 mins, while a human genome can be sequenced at 15 times coverage in a matter of days.
More recent, third-generation DNA sequencers such as PacBio SMRT and Oxford Nanopore offer the possibility of sequencing long molecules, compared to short-read technologies such as Illumina SBS or MGI Tech's DNBSEQ.
Because of limitations in DNA sequencer technology, the reads of many of these technologies are short, compared to the length of a genome therefore the reads must be assembled into longer contigs. The data may also contain errors, caused by limitations in the DNA sequencing technique or by errors during PCR amplification. DNA sequencer manufacturers use a number of different methods to detect which DNA bases are present. The specific protocols applied in different sequencing platforms have an impact in the final data that is generated. Therefore, comparing data quality and cost across different technologies can be a daunting task. Each manufacturer provides their own ways to inform sequencing errors and scores. However, errors and scores between different platforms cannot always be compared directly. Since these systems rely on different DNA sequencing approaches, choosing the best DNA sequencer and method will typically depend on the experiment objectives and available budget.
== History ==
The first DNA sequencing methods were developed by Gilbert (1973) and Sanger (1975). Gilbert introduced a sequencing method based on chemical modification of DNA followed by cleavage at specific bases whereas Sanger's technique is based on dideoxynucleotide chain termination. The Sanger method became popular due to its increased efficiency and low radioactivity. The first automated DNA sequencer was the AB370A, introduced in 1986 by Applied Biosystems. The AB370A was able to sequence 96 samples simultaneously, 500 kilobases per day, and reaching read lengths up to 600 bases. This was the beginning of the "first generation" of DNA sequencers, which implemented Sanger sequencing, fluorescent dideoxy nucleotides and polyacrylamide gel sandwiched between glass plates - slab gels. The next major advance was the release in 1995 of the AB310 which utilized a linear polymer in a capillary in place of the slab gel for DNA strand separation by electrophoresis. These techniques formed the base for the completion of the human genome project in 2001. The human genome project spurred the development of cheaper, high throughput and more accurate platforms known as Next Generation Sequencers (NGS). In 2005, 454 Life Sciences released the 454 sequencer, followed by Solexa Genome Analyzer and SOLiD (Supported Oligo Ligation Detection) by Agencourt in 2006. Applied Biosystems acquired Agencourt in 2006, and in 2007, Roche bought 454 Life Sciences, while Illumina purchased Solexa. Ion Torrent entered the market in 2010 and was acquired by Life Technologies (now Thermo Fisher Scientific). And BGI started manufacturing sequencers in China after acquiring Complete Genomics under their MGI arm. These are still the most common NGS systems due to their competitive cost, accuracy, and performance.
More recently, a third generation of DNA sequencers was introduced. The sequencing methods applied by these sequencers do not require DNA amplification (polymerase chain reaction – PCR), which speeds up the sample preparation before sequencing and reduces errors. In addition, sequencing data is collected from the reactions caused by the addition of nucleotides in the complementary strand in real time. Two companies introduced different approaches in their third-generation sequencers. Pacific Biosciences sequencers utilize a method called Single-molecule real-time (SMRT), where sequencing data is produced by light (captured by a camera) emitted when a nucleotide is added to the complementary strand by enzymes containing fluorescent dyes. Oxford Nanopore Technologies is another company developing third-generation sequencers using electronic systems based on nanopore sensing technologies.
== Manufacturers of DNA sequencers ==
DNA sequencers have been developed, manufactured, and sold by the following companies, among others.
=== Roche ===
The 454 DNA sequencer was the first next-generation sequencer to become commercially successful. It was developed by 454 Life Sciences and purchased by Roche in 2007. 454 utilizes the detection of pyrophosphate released by the DNA polymerase reaction when adding a nucleotide to the template strain.
Roche currently manufactures two systems based on their pyrosequencing technology: the GS FLX+ and the GS Junior System. The GS FLX+ System promises read lengths of approximately 1000 base pairs while the GS Junior System promises 400 base pair reads. A predecessor to GS FLX+, the 454 GS FLX Titanium system was released in 2008, achieving an output of 0.7G of data per run, with 99.9% accuracy after quality filter, and a read length of up to 700bp. In 2009, Roche launched the GS Junior, a bench top version of the 454 sequencer with read length up to 400bp, and simplified library preparation and data processing.
One of the advantages of 454 systems is their running speed. Manpower can be reduced with automation of library preparation and semi-automation of emulsion PCR. A disadvantage of the 454 system is that it is prone to errors when estimating the number of bases in a long string of identical nucleotides. This is referred to as a homopolymer error and occurs when there are 6 or more identical bases in row. Another disadvantage is that the price of reagents is relatively more expensive compared with other next-generation sequencers.
In 2013 Roche announced that they would be shutting down development of 454 technology and phasing out 454 machines completely in 2016 when its technology became noncompetitive.
Roche produces a number of software tools which are optimised for the analysis of 454 sequencing data. Such as,
GS Run Processor converts raw images generated by a sequencing run into intensity values. The process consists of two main steps: image processing and signal processing. The software also applies normalization, signal correction, base-calling and quality scores for individual reads. The software outputs data in Standard Flowgram Format (or SFF) files to be used in data analysis applications (GS De Novo Assembler, GS Reference Mapper or GS Amplicon Variant Analyzer).
GS De Novo Assembler is a tool for de novo assembly of whole-genomes up to 3GB in size from shotgun reads alone or combined with paired end data generated by 454 sequencers. It also supports de novo assembly of transcripts (including analysis), and also isoform variant detection.
GS Reference Mapper maps short reads to a reference genome, generating a consensus sequence. The software is able to generate output files for assessment, indicating insertions, deletions and SNPs. Can handle large and complex genomes of any size.
Finally, the GS Amplicon Variant Analyzer aligns reads from amplicon samples against a reference, identifying variants (linked or not) and their frequencies. It can also be used to detect unknown and low-frequency variants. It includes graphical tools for analysis of alignments.
=== Illumina ===
Illumina produces a number of next-generation sequencing machines using technology acquired from Manteia Predictive Medicine and developed by Solexa. Illumina makes a number of next generation sequencing machines using this technology including the HiSeq, Genome Analyzer IIx, MiSeq and the HiScanSQ, which can also process microarrays.
The technology leading to these DNA sequencers was first released by Solexa in 2006 as the Genome Analyzer. Illumina purchased Solexa in 2007. The Genome Analyzer uses a sequencing by synthesis method. The first model produced 1G per run. During the year 2009 the output was increased from 20G per run in August to 50G per run in December. In 2010 Illumina released the HiSeq 2000 with an output of 200 and then 600G per run which would take 8 days. At its release the HiSeq 2000 provided one of the cheapest sequencing platforms at $0.02 per million bases as costed by the Beijing Genomics Institute.
In 2011 Illumina released a benchtop sequencer called the MiSeq. At its release the MiSeq could generate 1.5G per run with paired end 150bp reads. A sequencing run can be performed in 10 hours when using automated DNA sample preparation.
The Illumina HiSeq uses two software tools to calculate the number and position of DNA clusters to assess the sequencing quality: the HiSeq control system and the real-time analyzer. These methods help to assess if nearby clusters are interfering with each other.
=== Life Technologies ===
Life Technologies (now Thermo Fisher Scientific) produces DNA sequencers under the Applied Biosystems and Ion Torrent brands. Applied Biosystems makes the SOLiD next-generation sequencing platform, and Sanger-based DNA sequencers such as the 3500 Genetic Analyzer. Under the Ion Torrent brand, Applied Biosystems produces four next-generation sequencers: the Ion PGM System, Ion Proton System, Ion S5 and Ion S5xl systems. The company is also believed to be developing their new capillary DNA sequencer called SeqStudio that will be released early 2018.
SOLiD systems was acquired by Applied Biosystems in 2006. SOLiD applies sequencing by ligation and dual base encoding. The first SOLiD system was launched in 2007, generating reading lengths of 35bp and 3G data per run. After five upgrades, the 5500xl sequencing system was released in 2010, considerably increasing read length to 85bp, improving accuracy up to 99.99% and producing 30G per 7-day run.
The limited read length of the SOLiD has remained a significant shortcoming and has to some extent limited its use to experiments where read length is less vital such as resequencing and transcriptome analysis and more recently ChIP-Seq and methylation experiments. The DNA sample preparation time for SOLiD systems has become much quicker with the automation of sequencing library preparations such as the Tecan system.
The colour space data produced by the SOLiD platform can be decoded into DNA bases for further analysis, however software that considers the original colour space information can give more accurate results. Life Technologies has released BioScope, a data analysis package for resequencing, ChiP-Seq and transcriptome analysis. It uses the MaxMapper algorithm to map the colour space reads.
=== Beckman Coulter ===
Beckman Coulter (now Danaher) has previously manufactured chain termination and capillary electrophoresis-based DNA sequencers under the model name CEQ, including the CEQ 8000. The company now produces the GeXP Genetic Analysis System, which uses dye terminator sequencing. This method uses a thermocycler in much the same way as PCR to denature, anneal, and extend DNA fragments, amplifying the sequenced fragments.
=== Pacific Biosciences ===
Pacific Biosciences produces the PacBio RS and Sequel sequencing systems using a single molecule real time sequencing, or SMRT, method. This system can produce read lengths of multiple thousands of base pairs. Higher raw read errors are corrected using either circular consensus - where the same strand is read over and over again - or using optimized assembly strategies. Scientists have reported 99.9999% accuracy with these strategies. The Sequel system was launched in 2015 with an increased capacity and a lower price.
=== Oxford Nanopore ===
Oxford Nanopore Technologies' MinION sequencer is based on evolving nanopore sequencing technology to nucleic acid analyses. The device is four inches long and gets power from a USB port. MinION decodes DNA directly as the molecule is drawn at the rate of 450 bases/second through a nanopore suspended in a membrane. Changes in electric current indicate which base is present. Initially, the device was 60 to 85 percent accurate, compared with 99.9 percent in conventional machines. Even inaccurate results may prove useful because it produces long read lengths. In early 2021, researchers from University of British Columbia has used special molecular tags and able to reduce the five-to-15 per cent error rate of the device to less than 0.005 per cent even when sequencing many long stretches of DNA at a time. There are two more product iterations based on MinION; the first one is the GridION which is a slightly larger sequencer that processes up to five MinION flow cells at once. And, the second one is the PromethION which uses as many as 100,000 pores in parallel, more suitable for high volume sequencing.
=== MGI ===
MGI produces high-throughput sequencers for scientific research and clinical applications such as DNBSEQ-G50, DNBSEQ-G400, and DNBSEQ-T7, under a proprietary DNBSEQ technology. It is based upon DNA nanoball sequencing and combinatorial probe anchor synthesis technologies, in which DNA nanoballs (DNBs) are loaded onto a patterned array chip via the fluidic system, and later a sequencing primer is added to the adaptor region of DNBs for hybridization. DNBSEQ-T7 can generate short reads at a very large scale—up to 60 human genomes per day. DNBSEQ-T7 was used to generate 150 bp paired-end reads, sequencing 30X, to sequence the genome of SARS-CoV-2 or COVID-19 to identify the genetic variants predisposition in severe COVID-19 illness. Using a novel technique the researchers from China National GeneBank sequenced PCR-free libraries on MGI's PCR-free DNBSEQ arrays to obtain for the first time a true PCR-free whole genome sequencing. MGISEQ-2000 was used in single-cell RNA sequencing to study the underlying pathogenesis and recovery in COVID-19 patients, as published in Nature Medicine.
== Comparison ==
Current offerings in DNA sequencing technology show a dominant player: Illumina (December 2019), followed by PacBio, MGI and Oxford Nanopore.
== References == | Wikipedia/DNA_sequencers |
DNA sequencing theory is the broad body of work that attempts to lay analytical foundations for determining the order of specific nucleotides in a sequence of DNA, otherwise known as DNA sequencing. The practical aspects revolve around designing and optimizing sequencing projects (known as "strategic genomics"), predicting project performance, troubleshooting experimental results, characterizing factors such as sequence bias and the effects of software processing algorithms, and comparing various sequencing methods to one another. In this sense, it could be considered a branch of systems engineering or operations research. The permanent archive of work is primarily mathematical, although numerical calculations are often conducted for particular problems too. DNA sequencing theory addresses physical processes related to sequencing DNA and should not be confused with theories of analyzing resultant DNA sequences, e.g. sequence alignment. Publications sometimes do not make a careful distinction, but the latter are primarily concerned with algorithmic issues. Sequencing theory is based on elements of mathematics, biology, and systems engineering, so it is highly interdisciplinary. The subject may be studied within the context of computational biology.
== Theory and sequencing strategies ==
=== Sequencing as a covering problem ===
All mainstream methods of DNA sequencing rely on reading small fragments of DNA and subsequently reconstructing these data to infer the original DNA target, either via assembly or alignment to a reference. The abstraction common to these methods is that of a mathematical covering problem. For example, one can imagine a line segment representing the target and a subsequent process where smaller segments are "dropped" onto random locations of the target. The target is considered "sequenced" when adequate coverage accumulates (e.g., when no gaps remain).
The abstract properties of covering have been studied by mathematicians for over a century. However, direct application of these results has not generally been possible. Closed-form mathematical solutions, especially for probability distributions, often cannot be readily evaluated. That is, they involve inordinately large amounts of computer time for parameters characteristic of DNA sequencing. Stevens' configuration is one such example. Results obtained from the perspective of pure mathematics also do not account for factors that are actually important in sequencing, for instance detectable overlap in sequencing fragments, double-stranding, edge-effects, and target multiplicity. Consequently, development of sequencing theory has proceeded more according to the philosophy of applied mathematics. In particular, it has been problem-focused and makes expedient use of approximations, simulations, etc.
=== Early uses derived from elementary probability theory ===
The earliest result may be found directly from elementary probability theory. Suppose we model the above process taking
L
{\displaystyle L}
and
G
{\displaystyle G}
as the fragment length and target length, respectively. The probability of "covering" any given location on the target with one particular fragment is then
L
/
G
{\displaystyle L/G}
. (This presumes
L
≪
G
{\displaystyle L\ll G}
, which is valid often, but not for all real-world cases.) The probability of a single fragment not covering a given location on the target is therefore
1
−
L
/
G
{\displaystyle 1-L/G}
, and
[
1
−
L
/
G
]
N
{\displaystyle \left[1-L/G\right]^{N}}
for
N
{\displaystyle N}
fragments. The probability of covering a given location on the target with at least one fragment is therefore
P
=
1
−
[
1
−
L
G
]
N
.
{\displaystyle P=1-\left[1-{\frac {L}{G}}\right]^{N}.}
This equation was first used to characterize plasmid libraries, but it may appear in a modified form. For most projects
N
≫
1
{\displaystyle N\gg 1}
, so that, to a good degree of approximation
[
1
−
L
G
]
N
∼
exp
(
−
N
L
/
G
)
,
{\displaystyle \left[1-{\frac {L}{G}}\right]^{N}\sim \exp(-NL/G),}
where
R
=
N
L
/
G
{\displaystyle R=NL/G}
is called the redundancy. Note the significance of redundancy as representing the average number of times a position is covered with fragments. Note also that in considering the covering process over all positions in the target, this probability is identical to the expected value of the random variable
C
{\displaystyle C}
, the fraction of the target coverage. The final result,
E
⟨
C
⟩
=
1
−
e
−
R
,
{\displaystyle E\langle C\rangle =1-e^{-R},}
remains in widespread use as a "back of the envelope" estimator and predicts that coverage for all projects evolves along a universal curve that is a function only of the redundancy.
=== Lander-Waterman theory ===
In 1988, Eric Lander and Michael Waterman published an important paper examining the covering problem from the standpoint of gaps. Although they focused on the so-called mapping problem, the abstraction to sequencing is much the same. They furnished a number of useful results that were adopted as the standard theory from the earliest days of "large-scale" genome sequencing. Their model was also used in designing the Human Genome Project and continues to play an important role in DNA sequencing.
Ultimately, the main goal of a sequencing project is to close all gaps, so the "gap perspective" was a logical basis of developing a sequencing model. One of the more frequently used results from this model is the expected number of contigs, given the number of fragments sequenced. If one neglects the amount of sequence that is essentially "wasted" by having to detect overlaps, their theory yields
E
⟨
c
o
n
t
i
g
s
⟩
=
N
e
−
R
.
{\displaystyle E\langle contigs\rangle =Ne^{-R}.}
In 1995, Roach published improvements to this theory, enabling it to be applied to sequencing projects in which the goal was to completely sequence a target genome. Michael Wendl and Bob Waterston confirmed, based on Stevens' method, that both models produced similar results when the number of contigs was substantial, such as in low coverage mapping or sequencing projects. As sequencing projects ramped up in the 1990s, and projects approached completion, low coverage approximations became inadequate, and the exact model of Roach was necessary. However, as the cost of sequencing dropped, parameters of sequencing projects became easier to directly test empirically, and interest and funding for strategic genomics diminished.
The basic ideas of Lander–Waterman theory led to a number of additional results for particular variations in mapping techniques. However, technological advancements have rendered mapping theories largely obsolete except in organisms other than highly studied model organisms (e.g., yeast, flies, mice, and humans).
=== Parking strategy ===
The parking strategy for sequencing resembles the process of parking cars along a curb. Each car is a sequenced clone, and the curb is the genomic target. Each clone sequenced is screened to ensure that subsequently sequenced clones do not overlap any previously sequenced clone. No sequencing effort is redundant in this strategy. However, much like the gaps between parked cars, unsequenced gaps less than the length of a clone accumulate between sequenced clones. There can be considerable cost to close such gaps.
=== Pairwise end-sequencing ===
In 1995, Roach et al. proposed and demonstrated through simulations a generalization of a set of strategies explored earlier by Edwards and Caskey. This whole-genome sequencing method became immensely popular as it was championed by Celera and used to sequence several model organisms before Celera applied it to the human genome. Today, most sequencing projects employ this strategy, often called paired end sequencing.
== Post Human Genome Project advancements ==
The physical processes and protocols of DNA sequencing have continued to evolve, largely driven by advancements in bio-chemical methods, instrumentation, and automation techniques. There is now a wide range of problems that DNA sequencing has made in-roads into, including metagenomics and medical (cancer) sequencing. There are important factors in these scenarios that classical theory does not account for. Recent work has begun to focus on resolving the effects of some of these issues. The level of mathematics becomes commensurately more sophisticated.
=== Various artifacts of large-insert sequencing ===
Biologists have developed methods to filter highly-repetitive, essentially un-sequenceable regions of genomes. These procedures are important for organisms whose genomes consist mostly of such DNA, for example corn. They yield multitudes of small islands of sequenceable DNA products. Wendl and Barbazuk proposed an extension to Lander–Waterman Theory to account for "gaps" in the target due to filtering and the so-called "edge-effect". The latter is a position-specific sampling bias, for example the terminal base position has only a
1
/
G
{\displaystyle 1/G}
chance of being covered, as opposed to
L
/
G
{\displaystyle L/G}
for interior positions. For
R
<
1
{\displaystyle R<1}
, classical Lander–Waterman Theory still gives good predictions, but dynamics change for higher redundancies.
Modern sequencing methods usually sequence both ends of a larger fragment, which provides linking information for de novo assembly and improved probabilities for alignment to reference sequence. Researchers generally believe that longer lengths of data (read lengths) enhance performance for very large DNA targets, an idea consistent with predictions from distribution models. However, Wendl showed that smaller fragments provide better coverage on small, linear targets because they reduce the edge effect in linear molecules. These findings have implications for sequencing the products of DNA filtering procedures. Read-pairing and fragment size evidently have negligible influence for large, whole-genome class targets.
=== Individual and population sequencing ===
Sequencing is emerging as an important tool in medicine, for example in cancer research. Here, the ability to detect heterozygous mutations is important and this can only be done if the sequence of the diploid genome is obtained. In the pioneering efforts to sequence individuals, Levy et al. and Wheeler et al., who sequenced Craig Venter and Jim Watson, respectively, outlined models for covering both alleles in a genome. Wendl and Wilson followed with a more general theory that allowed for an arbitrary number of coverings of each allele and arbitrary ploidy. These results point to the general conclusion that the amount of data needed for such projects is significantly higher than for traditional haploid projects. Generally, at least 30-fold redundancy, i.e. each nucleotide spanned by an average of 30 sequence reads, is now standard.
However, requirements can be even greater, depending upon what kinds of genomic events are to be found. For example, in the so-called "discordant read pairs method", DNA insertions can be inferred if the distance between read pairs is larger than expected. Calculations show that around 50-fold redundancy is needed to avoid false-positive errors at 1% threshold.
The advent of next-generation sequencing has also made large-scale population sequencing feasible, for example the 1000 Genomes Project to characterize variation in human population groups. While common variation is easily captured, rare variation poses a design challenge: too few samples with significant sequence redundancy risks not having a variant in the sample group, but large samples with light redundancy risk not capturing a variant in the read set that is actually in the sample group. Wendl and Wilson report a simple set of optimization rules that maximize the probability of discovery for a given set of parameters. For example, for observing a rare allele at least twice (to eliminate the possibility is unique to an individual) a little less than 4-fold redundancy should be used, regardless of the sample size.
=== Metagenomic sequencing ===
Next-generation instruments are now also enabling the sequencing of whole uncultured metagenomic communities. The sequencing scenario is more complicated here and there are various ways of framing design theories for a given project. For example, Stanhope developed a probabilistic model for the amount of sequence needed to obtain at least one contig of a given size from each novel organism of the community, while Wendl et al. reported analysis for the average contig size or the probability of completely recovering a novel organism for a given rareness within the community. Conversely, Hooper et al. propose a semi-empirical model based on the gamma distribution.
== Limitations ==
DNA sequencing theories often invoke the assumption that certain random variables in a model are independent and identically distributed. For example, in Lander–Waterman Theory, a sequenced fragment is presumed to have the same probability of covering each region of a genome and all fragments are assumed to be independent of one another. In actuality, sequencing projects are subject to various types of bias, including differences of how well regions can be cloned, sequencing anomalies, biases in the target sequence (which is not random), and software-dependent errors and biases. In general, theory will agree well with observation up to the point that enough data have been generated to expose latent biases. The kinds of biases related to the underlying target sequence are particularly difficult to model, since the sequence itself may not be known a priori. This presents a type of Catch-22 (logic) problem.
== See also ==
Computational biology
Bioinformatics
Mathematical biology
Sulston score
== References == | Wikipedia/DNA_sequencing_theory |
BMC Systems Biology was an open access peer-reviewed scientific journal that covered research in systems biology. Filling a gap in what was a new research field, the journal was established in 2007 and is published by BioMed Central. Part of the BMC Series of journals, it had a broad scope covering the engineering of biological systems, network modelling, quantitative analyses, integration of different levels of information and synthetic biology.
In January 2019, the Editorial Board was informed that the journal was closing and no more submissions would be accepted after March 1. The last articles were published on 5 April 2019, but content is still archived in perpetuity from the homepage and PubMed Central.
== Scope and Coverage ==
BMC Systems Biology focused on a wide range of topics within systems biology, including but not limited to:
Engineering of biological systems
Network modelling
Quantitative analyses
Integration of different levels of information
Synthetic biology
The journal provided a platform for the dissemination of significant research findings in the area of systems biology, aiming to bridge the gap between biological research and mathematical modelling.
== Notable Articles and Research ==
Several significant studies were published in the journal, contributing to the advancement of systems biology. Some notable research includes:
"A quantitative systems pharmacology (QSP) model for Pneumocystis treatment in mice"
"Network-based characterization of drug-protein interaction signatures with a space-efficient approach"
"Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus"
== Impact and Legacy ==
The journal's impact factor in 2018 was 2.048, reflecting its influence and relevance in the field of systems biology. Although the journal is now closed, its archived content continues to serve as a valuable resource for researchers and scholars.
== See also ==
Systems and Synthetic Biology (until 2015)
== References == | Wikipedia/BMC_Systems_Biology |
A DNA field-effect transistor (DNAFET) is a field-effect transistor which uses the field-effect due to the partial charges of DNA molecules to function as a biosensor. The structure of DNAFETs is similar to that of MOSFETs, with the exception of the gate structure which, in DNAFETs, is replaced by a layer of immobilized ssDNA (single-stranded DNA) molecules which act as surface receptors. When complementary DNA strands hybridize to the receptors, the charge distribution near the surface changes, which in turn modulates current transport through the semiconductor transducer.
Arrays of DNAFETs can be used for detecting single nucleotide polymorphisms (causing many hereditary diseases) and for DNA sequencing. Their main advantage compared to optical detection methods in common use today is that they do not require labeling of molecules. Furthermore, they work continuously and (near) real-time. DNAFETs are highly selective since only specific binding modulates charge transport.
== References ==
Li Z, Chen Y, Li X, Kamins TI, Nauka K, Williams RS (2004). "Sequence-Specific Label-Free DNA Sensors Based on Silicon Nanowires". Nano Lett. 4 (2): 245–7. Bibcode:2004NanoL...4..245L. doi:10.1021/nl034958e.
Souteyrand E, Cloarec JP, Martin JR, Wilson C, Lawrence I, Mikkelsen S, Lawrence MF (1997). "Direct Detection of the Hybridization of Synthetic Homo-Oligomer DNA Sequences by Field Effect". J. Phys. Chem. B. 101 (15): 2980–5. doi:10.1021/jp963056h.
Fritz J, Cooper EB, Gaudet S, Sorger PK, Manalis SR (October 2002). "Electronic detection of DNA by its intrinsic molecular charge". Proc. Natl. Acad. Sci. U.S.A. 99 (22): 14142–6. Bibcode:2002PNAS...9914142F. doi:10.1073/pnas.232276699. PMC 137851. PMID 12386345. | Wikipedia/DNA_field-effect_transistor |
DNA nanoball sequencing (DNBSEQ) is a high throughput sequencing technology that is used to determine the entire genomic sequence of an organism. The method uses rolling circle replication to amplify small fragments of genomic DNA into DNA nanoballs. Fluorescent nucleotides bind to complementary nucleotides and are then polymerized to anchor sequences bound to known sequences on the DNA template. The base order is determined via the fluorescence of the bound nucleotides This DNA sequencing method allows large numbers of DNA nanoballs to be sequenced per run at lower reagent costs compared to other next generation sequencing platforms. However, a limitation of this method is that it generates only short sequences of DNA, which presents challenges to mapping its reads to a reference genome. After purchasing Complete Genomics, the Beijing Genomics Institute (BGI) refined DNA nanoball sequencing to sequence nucleotide samples on their own platform.
== Procedure ==
DNA Nanoball Sequencing involves isolating DNA that is to be sequenced, shearing it into small 100 – 350 base pair (bp) fragments, ligating adapter sequences to the fragments, and circularizing the fragments. The circular fragments are copied by rolling circle replication resulting in many single-stranded copies of each fragment. The DNA copies concatenate head to tail in a long strand, and are compacted into a DNA nanoball. The nanoballs are then adsorbed onto a sequencing flow cell. The color of the fluorescence at each interrogated position is recorded through a high-resolution camera. Bioinformatics are used to analyze the fluorescence data and make a base call, and for mapping or quantifying the 50bp, 100bp, or 150bp single- or paired-end reads.
=== DNA Isolation, fragmentation, and size capture ===
Cells are lysed and DNA is extracted from the cell lysate. The high-molecular-weight DNA, often several megabase pairs long, is fragmented by physical or enzymatic methods to break the DNA double-strands at random intervals. Bioinformatic mapping of the sequencing reads is most efficient when the sample DNA contains a narrow length range. For small RNA sequencing, selection of the ideal fragment lengths for sequencing is performed by gel electrophoresis; for sequencing of larger fragments, DNA fragments are separated by bead-based size selection.
=== Attaching adapter sequences ===
Adapter DNA sequences must be attached to the unknown DNA fragment so that DNA segments with known sequences flank the unknown DNA. In the first round of adapter ligation, right (Ad153_right) and left (Ad153_left) adapters are attached to the right and left flanks of the fragmented DNA, and the DNA is amplified by PCR. A splint oligo then hybridizes to the ends of the fragments which are ligated to form a circle. An exonuclease is added to remove all remaining linear single-stranded and double-stranded DNA products. The result is a completed circular DNA template.
=== Rolling circle replication ===
Once a single-stranded circular DNA template is created, containing sample DNA that is ligated to two unique adapter sequences has been generated, the full sequence is amplified into a long string of DNA. This is accomplished by rolling circle replication with the Phi 29 DNA polymerase which binds and replicates the DNA template. The newly synthesized strand is released from the circular template, resulting in a long single-stranded DNA comprising several head-to-tail copies of the circular template. The resulting nanoparticle self-assembles into a tight ball of DNA approximately 300 nanometers (nm) across. Nanoballs remain separated from each other because they are negatively charged naturally repel each other, reducing any tangling between different single stranded DNA lengths.
=== DNA nanoball patterned array ===
To obtain DNA sequence, the DNA nanoballs are attached to a patterned array flow cell. The flow cell is a silicon wafer coated with silicon dioxide, titanium, hexamethyldisilazane (HMDS), and a photoresist material. The DNA nanoballs are added to the flow cell and selectively bind to the positively-charged aminosilane in a highly ordered pattern, allowing a very high density of DNA nanoballs to be sequenced.
=== Imaging ===
After each DNA nucleotide incorporation step, the flow cell is imaged to determine which nucleotide base bound to the DNA nanoball. The fluorophore is excited with a laser that excites specific wavelengths of light. The emission of fluorescence from each DNA nanoball is captured on a high resolution CCD camera. The image is then processed to remove background noise and assess the intensity of each point. The color of each DNA nanoball corresponds to a base at the interrogative position and a computer records the base position information.
=== Sequencing data format ===
The data generated from the DNA nanoballs is formatted as standard FASTQ formatted files with contiguous bases (no gaps). These files can be used in any data analysis pipeline that is configured to read single-end or paired-end FASTQ files.
For example:
Read 1, from a 100bp paired end run from
@CL100011513L1C001R013_126365/1
CTAGGCAACTATAGGTCTCAGTTAAGTCAAATAAAATTCACATCAAATTTTTACTCCCACCATCCCAACACTTTCCTGCCTGGCATATGCCGTGTCTGCC
+
FFFFFFFFFFFGFGFFFFFF;FFFFFFFGFGFGFFFFFF;FFFFGFGFGFFEFFFFFEDGFDFF@FCFGFGCFFFFFEFFEGDFDFFFFFGDAFFEFGFF
Corresponding Read 2:
@CL100011513L1C001R013_126365/2
TGTCTACCATATTCTACATTCCACACTCGGTGAGGGAAGGTAGGCACATAAAGCAATGGCAGTACGGTGTAATACATGCTAATGTAGAGTAAGCACTCAG
+
3E9E<ADEBB:D>E?FD<<@EFE>>ECEF5CE:B6E:CEE?6B>B+@??31/FD:0?@:E9<3FE2/A:/8>9CB&=E<7:-+>;29:7+/5D9)?5F/:
== Informatics Tips ==
=== Reference Genome Alignment ===
Default parameters for the popular aligners are sufficient.
=== Read Names ===
In the FASTQ file created by BGI/MGI sequencers using DNA nanoballs on a patterned array flowcell, the read names look like this:
BGISEQ-500:
CL100025298L1C002R050_244547
MGISEQ-2000:
V100006430L1C001R018613883
Read names can be parsed to extract three variables describing the physical location of the read on the patterned array: (1) tile/region, (2) x coordinate, and (3) y coordinate. Note that, due to the order of these variables, these read names cannot be natively parsed by Picard MarkDuplicates in order to identify optical duplicates. However, as there are none on this platform, this poses no problem to Picard-based data analysis.
=== Duplicates ===
Because DNA nanoballs remain confined their spots on the patterned array there are no optical duplicates to contend with during bioinformatics analysis of sequencing reads. It is suggested to run Picard MarkDuplicates as follows:
java -jar picard.jar MarkDuplicates I=input.bam O=marked_duplicates.bam M=marked_dup_metrics.txt READ_NAME_REGEX=null
A test with Picard-friendly, reformatted read names demonstrates the absence of this class of duplicate read:
The single read marked as an optical duplicate is most assuredly artefactual. In any case, the effect on the estimated library size is negligible.
== Advantages ==
DNA nanoball sequencing technology offers some advantages over other sequencing platforms. One advantage is the eradication of optical duplicates. DNA nanoballs remain in place on the patterned array and do not interfere with neighboring nanoballs.
Another advantage of DNA nanoball sequencing include the use of high-fidelity Phi 29 DNA polymerase to ensure accurate amplification of the circular template, several hundred copies of the circular template compacted into a small area resulting in an intense signal, and attachment of the fluorophore to the probe at a long distance from the ligation point results in improved ligation.
== Disadvantages ==
The main disadvantage of DNA nanoball sequencing is the short read length of the DNA sequences obtained with this method. Short reads, especially for DNA high in DNA repeats, may map to two or more regions of the reference genome. A second disadvantage of this method is that multiple rounds of PCR have to be used. This can introduce PCR bias and possibly amplify contaminants in the template construction phase. However, these disadvantages are common to all short-read sequencing platforms are not specific to DNA nanoballs.
== Applications ==
DNA nanoball sequencing has been used in recent studies. Lee et al. used this technology to find mutations that were present in a lung cancer and compared them to normal lung tissue. They were able to identify over 50,000 single nucleotide variants. Roach et al. used DNA nanoball sequencing to sequence the genomes of a family of four relatives and were able to identify SNPs that may be responsible for a Mendelian disorder, and were able to estimate the inter-generation mutation rate. The Institute for Systems Biology has used this technology to sequence 615 complete human genome samples as part of a survey studying neurodegenerative diseases, and the National Cancer Institute is using DNA nanoball sequencing to sequence 50 tumours and matched normal tissues from pediatric cancers.
== Significance ==
Massively parallel next generation sequencing platforms like DNA nanoball sequencing may contribute to the diagnosis and treatment of many genetic diseases. The cost of sequencing an entire human genome has fallen from about one million dollars in 2008, to $4400 in 2010 with the DNA nanoball technology. Sequencing the entire genomes of patients with heritable diseases or cancer, mutations associated with these diseases have been identified, opening up strategies, such as targeted therapeutics for at-risk people and for genetic counseling. As the price of sequencing an entire human genome approaches the $1000 mark, genomic sequencing of every individual may become feasible as part of normal preventative medicine.
== References == | Wikipedia/DNA_nanoball_sequencing |
Magnetic sequencing is a single-molecule sequencing method in development. A DNA hairpin, containing the sequence of interest, is bound between a magnetic bead and a glass surface. A magnetic field is applied to stretch the hairpin open into single strands, and the hairpin refolds after decreasing of the magnetic field. The hairpin length can be determined by direct imaging of the diffraction rings of the magnetic beads using a simple microscope. The DNA sequences are determined by measuring the changes in the hairpin length following successful hybridization of complementary nucleotides.
== Single-molecule sequencing vs. Next-generation sequencing ==
With the development of various next-generation sequencing platforms, there has been a substantial reduction in costs, and increase in throughput of DNA sequencing. However, the majority of the sequencing technologies rely on PCR-based clonal amplification of the DNA molecule in order to bring the signal to a detectable range. Sequencing of amplified clusters, or bulk sequencing in such a propose a read length-dependent phasing problem. During each cycle, not all of the molecules within the bulk have successful incorporation of an additional nucleotide. With increased sequencing cycle, the signal of the lagging molecules will eventually overwhelm the true signal. The phasing problem is a major limitation for the read lengths of the next-generation sequencing technologies. Therefore, there is an increased interest in developing single-molecule sequencing technologies, where no amplification is required. This not only shortens the preparation time for the sequencing libraries, it also has the potential to achieve much longer read lengths, as the lagging molecules with failed extensions can be ignored or considered separately. Previously known single-molecule sequencing technologies include Nanopore sequencing (Oxford Nanopore),
SMRT sequencing (Pacific Biosciences), and Heliscope single molecule sequencing (Helicos Biosciences).
== Magnetic detection of oligonucleotides hybridized to the DNA hairpin ==
=== Generation of DNA hairpin ===
The DNA molecule of interest must be incorporated into a hairpin, and attached to a magnetic bead on one end and to an immobile glass surface on the other end. The hairpin is attached to the glass surface via a digoxigenin-antidigoxigenin bond. The magnetic bead is attached to the opposite end via biotin-streptavidin interaction. Such DNA hairpin setup can be made in two ways:
1) In the case of double-stranded DNA molecules (for whole genome sequencing, or targeted sequencing), the DNA fragment is ligated to a DNA loop at one end and a DNA fork structure, labeled with biotin and digoxigenin at the two ends.
2) For RNA-seq, the mRNA can be trapped on a poly-T-coated bead, where reverse transcription reaction is performed on the bead to generate a cDNA hairpin.
=== Measurement of hairpin length ===
Electromagnets are placed above the sample slide, and an inverted microscope is placed below. The image is captured via a CCD camera and transferred to a computer, where the three-dimensional positions of the magnetic beads are determined. The position of the bead within the horizontal plane of the glass slide, x and y, are determined by real-time correlation of the bead images. The vertical length of the hairpin, measured by the vertical position of the attached magnetic bead, is measured by the bead’s diffraction ring diameter, which increases with distance.
=== Opening and closing of DNA hairpin ===
A constant magnetic force is applied to unzip the DNA hairpin, and reducing the force allows the hairpin to rezip. Prior to performing the downstream applications several unzipping and rezipping cycles are performed. While the magnetic force required to unzip and rezip may vary depending on the DNA sequence and hairpin length, their absolute values are not critical as long as they are consistent within a sequencing run.
=== Detection of hybridization events ===
When the DNA hairpin is unzipped into single-strand, oligonucleotides complementary to the hairpin sequence are allowed to hybridize. During the time course of the rezipping process, the bound oligonucleotides cause transient blockages. The time course measurement of hairpin length allows for the determination of the exact position of the hybridization, as well as the presence of mismatches between the oligonucleotide and the hairpin.
== Applications for hairpin length detection in sequencing ==
=== Sequencing by hybridization ===
Hybridization is one way to determine the sequence of a DNA strand from detecting the changes in the length of a hairpin. When a probe hybridizes to an open hairpin, complete refolding of the hairpin is stalled, and the position of the hybridized probe can be inferred. Thus the sequence of a DNA fragment of interest can be inferred from overlapping the positions of probes sets, which are allowed to hybridize one by one.
==== Generation of 8-nt sequence ====
First, a DNA fragment can be converted into a new sequence in which each original nucleotide is encoded by a specific 8-nt sequence (A8, T8, G8 and C8) and then ligated to a hairpin.
==== Hybridization of A8, T8, C8, G8 oligonucleotides ====
After applying a magnetic force, in the unzipped state of the hairpin, a small number of discriminating nucleotides can hybridize to the new individual complementary sequences on the hairpin which can transiently block the refolding of the hairpin.
==== Map positions ====
Identification of the blockage positions of the hairpin produced by the hybridization of the discriminating nucleotides can be observed as the pauses in the time course of the hairpin distance measurement. The complete sequence can be reconstructed by the overlapping fragments.
==== Sequencing by ligation ====
Another application for the magnetic sequencing is using the hairpin end-to-end distance to detect the successive ligation of oligonucleotide. First step of sequencing by ligation is using a primer to extend a DNA fragment. Extension is first attempted with a fragment starting with adenine, which can only be ligated if the next nucleotide on the opposite strand is a thymine. Then fragments starting with cytosine, guanine and thymine are attempted in turn, and the cycle is repeated. The magnetic field is released after each ligation, and then the length of the extended primer is measured. Upon ligation the primer is extended by seven bases, which is resulting in a detectable increase in the hairpin’s end to end distance. RNase cleavage at position 2 is followed by the ligation for the preparation of the next ligation cycle, so that the next ligation is positioned just ahead of the previous one.
===== 7nt primer library =====
7-nt primer library, 5′-NNNNNNrX-3′, are used in the ligation of a short degenerate oligonucleotide fragmentin, in which N represents any of the four deoxyribonucleotides and Nr represents any of the four ribonucleotides, X is the tested base(A,G,C,T). The ligation to a primer strand of each of the four tested bases in hairpin opening and closing cycles are tested.
===== Ligation =====
7-nt primer ligates in the open state of the hairpin, which will block rezipping of the last seven nucleotides and increase the distance between the surface and the magnetic bead by ~5 nm. If the ligation is not successful, no change in the hairpin length is observed.
===== RNase =====
RNase cleavage of the last six nucleotides is the next step following the ligation, ultimately extending the primer strand by a single base. Such cleavage allows rezipping of 6 nucleotides of the hairpin, signaled by a decrease in hairpin length of ~4 nm. Therefore, an incorporation of a complementary nucleotide is indicated by an increase in 7 nucleotides (+5 nm) followed by a decrease in 6 nucleotides (-4 nm).
===== Kinase =====
After the RNase cleavage of the last six nucleotides, the next step is phosphorylation of the 5'-end via Kinase. Then the next cycle of ligation can be repeated.
== Advantages of the magnetic method in single-molecule sequencing ==
=== Nature of the detected signal ===
Many of the competitive single-molecule sequencing methods rely on the incorporation of fluorescently labeled nucleotides. In next-generation sequencing, the fluorescence signal of clusters can be easily detected. However, when the same concept is applied to single-molecule sequencing, the largest complication results from the high error rates. Because it is difficult to detect single labeled molecules, these platforms suffer from low signal-to-noise ratios, often resulting in misdetection or non-detection of fluorescent signals. In the case of magnetic sequencing, the signal measured is the changes in distance between two ends of a hairpin. Such signal can be readily detected with standard cameras. Thus, the signals are easier to detect, even without the use of expensive imaging devices.
=== Relaxation of the experimental constraints for single-nucleotide discrimination ===
In addition to the nature of the detected signal, other implementations in this platform allows for an even higher signal-to-noise ratio. In the case of magnetic sequencing by hybridization, a set of overlapping tiles is used such that the sequence of each nucleotide is determined by the hybridization of an 8-mer. Therefore, the instrument only requires the sensitivity to detect a change of ~ 6 nm (the length of 8 nucleotides). Similarly, for sequencing by ligation cycles, successful incorporation is characterized by a ~5 nm increase (ligation of a 7-mer) followed by a ~ 4 nm decrease (RNase cleavage of 6-mer) in hairpin length. In this case, the decrease in length in the second step provides additional confirmation for the obtained signal.
== Technical considerations ==
=== Resolution ===
With the current methods, the instrumental error in the measured hairpin length is 1-1.5 nm. The length of a basepair, or 2 extended single-stranded nucleotides, is approximately 0.85 nm. Therefore, the resolution of the system is at a few nucleotides. The sources of noise arise from length-dependent Brownian motion of the bead anchored by the extended hairpin, statistical error in bead position determination, and slow mechanical drifts. However, as mentioned earlier, such resolution is sufficient for the current sequencing method because changes in >4 nm are being measured.
=== Throughput ===
Through the use of magnetic traps, constant magnetic force can be applied to millions of DNA hairpin-tethered magnetic beads in parallel. The magnetic force can be easily adjusted by changing the distance between the trap and the magnetic beads. The number of eads that can be simultaneously monitored, which determines the read throughput of this platform, is limited by the bead size, length of the tethered DNA hairpin, and the optical resolution limit. Currently, a density of 750 K/mm2 (comparable to an Illumina HiSeq 2000) can be achieved.
=== Read length ===
As mentioned above, the noise due to the Brownian fluctuations of the bead increases with length. Robust sequencing tests have yet to be performed to determine the maximum read length of this system. However, the ligation of a 7-mer in the middle of a 1241 nucleotide-long hairpin was successfully detected, suggesting that the current system is sufficient to sequence up to ~500 bp.
=== Additional limitations ===
The rate of sequencing or imaging is dependent on the mechanical movement speed of the magnetic beads, which is limited by drag force. Currently, it is possible to measure 10 hairpin open-close cycle per second. Additional complications include the existence of a secondary hairpin structure in the DNA of interest. In such a case the DNA loop to be ligated must be designed such that it its closing is favored over the closing of the endogenous loop in the DNA of interest.
== References == | Wikipedia/Single-molecule_magnetic_sequencing |
A nucleic acid sequence is a succession of bases within the nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. This succession is denoted by a series of a set of five different letters that indicate the order of the nucleotides. By convention, sequences are usually presented from the 5' end to the 3' end. For DNA, with its double helix, there are two possible directions for the notated sequence; of these two, the sense strand is used. Because nucleic acids are normally linear (unbranched) polymers, specifying the sequence is equivalent to defining the covalent structure of the entire molecule. For this reason, the nucleic acid sequence is also termed the primary structure.
The sequence represents genetic information. Biological deoxyribonucleic acid represents the information which directs the functions of an organism.
Nucleic acids also have a secondary structure and tertiary structure. Primary structure is sometimes mistakenly referred to as "primary sequence". However there is no parallel concept of secondary or tertiary sequence.
== Nucleotides ==
Nucleic acids consist of a chain of linked units called nucleotides. Each nucleotide consists of three subunits: a phosphate group and a sugar (ribose in the case of RNA, deoxyribose in DNA) make up the backbone of the nucleic acid strand, and attached to the sugar is one of a set of nucleobases. The nucleobases are important in base pairing of strands to form higher-level secondary and tertiary structures such as the famed double helix.
The possible letters are A, C, G, and T, representing the four nucleotide bases of a DNA strand – adenine, cytosine, guanine, thymine – covalently linked to a phosphodiester backbone. In the typical case, the sequences are printed abutting one another without gaps, as in the sequence AAAGTCTGAC, read left to right in the 5' to 3' direction. With regards to transcription, a sequence is on the coding strand if it has the same order as the transcribed RNA.
One sequence can be complementary to another sequence, meaning that they have the base on each position in the complementary (i.e., A to T, C to G) and in the reverse order. For example, the complementary sequence to TTAC is GTAA. If one strand of the double-stranded DNA is considered the sense strand, then the other strand, considered the antisense strand, will have the complementary sequence to the sense strand.
=== Notation ===
While A, T, C, and G represent a particular nucleotide at a position, there are also letters that represent ambiguity which are used when more than one kind of nucleotide could occur at that position. The rules of the International Union of Pure and Applied Chemistry (IUPAC) are as follows:
For example, W means that either an adenine or a thymine could occur in that position without impairing the sequence's functionality.
These symbols are also valid for RNA, except with U (uracil) replacing T (thymine).
Apart from adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U), DNA and RNA also contain bases that have been modified after the nucleic acid chain has been formed. In DNA, the most common modified base is 5-methylcytidine (m5C). In RNA, there are many modified bases, including pseudouridine (Ψ), dihydrouridine (D), inosine (I), ribothymidine (rT) and 7-methylguanosine (m7G). Hypoxanthine and xanthine are two of the many bases created through mutagen presence, both of them through deamination (replacement of the amine-group with a carbonyl-group). Hypoxanthine is produced from adenine, and xanthine is produced from guanine. Similarly, deamination of cytosine results in uracil.
Example of comparing and determining the % difference between two nucleotide sequences
AATCCGCTAG
AAACCCTTAG
Given the two 10-nucleotide sequences, line them up and compare the differences between them. Calculate the percent difference by taking the number of differences between the DNA bases divided by the total number of nucleotides. In this case there are three differences in the 10 nucleotide sequence. Thus there is a 30% difference.
== Biological significance ==
In biological systems, nucleic acids contain information which is used by a living cell to construct specific proteins. The sequence of nucleobases on a nucleic acid strand is translated by cell machinery into a sequence of amino acids making up a protein strand. Each group of three bases, called a codon, corresponds to a single amino acid, and there is a specific genetic code by which each possible combination of three bases corresponds to a specific amino acid.
The central dogma of molecular biology outlines the mechanism by which proteins are constructed using information contained in nucleic acids. DNA is transcribed into mRNA molecules, which travel to the ribosome where the mRNA is used as a template for the construction of the protein strand. Since nucleic acids can bind to molecules with complementary sequences, there is a distinction between "sense" sequences which code for proteins, and the complementary "antisense" sequence, which is by itself nonfunctional, but can bind to the sense strand.
== Sequence determination ==
DNA sequencing is the process of determining the nucleotide sequence of a given DNA fragment. The sequence of the DNA of a living thing encodes the necessary information for that living thing to survive and reproduce. Therefore, determining the sequence is useful in fundamental research into why and how organisms live, as well as in applied subjects. Because of the importance of DNA to living things, knowledge of a DNA sequence may be useful in practically any biological research. For example, in medicine it can be used to identify, diagnose and potentially develop treatments for genetic diseases. Similarly, research into pathogens may lead to treatments for contagious diseases. Biotechnology is a burgeoning discipline, with the potential for many useful products and services.
RNA is not sequenced directly. Instead, it is copied to a DNA by reverse transcriptase, and this DNA is then sequenced.
Current sequencing methods rely on the discriminatory ability of DNA polymerases, and therefore can only distinguish four bases. An inosine (created from adenosine during RNA editing) is read as a G, and 5-methyl-cytosine (created from cytosine by DNA methylation) is read as a C. With current technology, it is difficult to sequence small amounts of DNA, as the signal is too weak to measure. This is overcome by polymerase chain reaction (PCR) amplification.
=== Digital representation ===
Once a nucleic acid sequence has been obtained from an organism, it is stored in silico in digital format. Digital genetic sequences may be stored in sequence databases, be analyzed (see Sequence analysis below), be digitally altered and be used as templates for creating new actual DNA using artificial gene synthesis.
== Sequence analysis ==
Digital genetic sequences may be analyzed using the tools of bioinformatics to attempt to determine its function.
=== Genetic testing ===
The DNA in an organism's genome can be analyzed to diagnose vulnerabilities to inherited diseases, and can also be used to determine a child's paternity (genetic father) or a person's ancestry. Normally, every person carries two variations of every gene, one inherited from their mother, the other inherited from their father. The human genome is believed to contain around 20,000–25,000 genes. In addition to studying chromosomes to the level of individual genes, genetic testing in a broader sense includes biochemical tests for the possible presence of genetic diseases, or mutant forms of genes associated with increased risk of developing genetic disorders.
Genetic testing identifies changes in chromosomes, genes, or proteins. Usually, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use, and more are being developed.
=== Sequence alignment ===
In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be due to functional, structural, or evolutionary relationships between the sequences. If two sequences in an alignment share a common ancestor, mismatches can be interpreted as point mutations and gaps as insertion or deletion mutations (indels) introduced in one or both lineages in the time since they diverged from one another. In sequence alignments of proteins, the degree of similarity between amino acids occupying a particular position in the sequence can be interpreted as a rough measure of how conserved a particular region or sequence motif is among lineages. The absence of substitutions, or the presence of only very conservative substitutions (that is, the substitution of amino acids whose side chains have similar biochemical properties) in a particular region of the sequence, suggest that this region has structural or functional importance. Although DNA and RNA nucleotide bases are more similar to each other than are amino acids, the conservation of base pairs can indicate a similar functional or structural role.
Computational phylogenetics makes extensive use of sequence alignments in the construction and interpretation of phylogenetic trees, which are used to classify the evolutionary relationships between homologous genes represented in the genomes of divergent species. The degree to which sequences in a query set differ is qualitatively related to the sequences' evolutionary distance from one another. Roughly speaking, high sequence identity suggests that the sequences in question have a comparatively young most recent common ancestor, while low identity suggests that the divergence is more ancient. This approximation, which reflects the "molecular clock" hypothesis that a roughly constant rate of evolutionary change can be used to extrapolate the elapsed time since two genes first diverged (that is, the coalescence time), assumes that the effects of mutation and selection are constant across sequence lineages. Therefore, it does not account for possible differences among organisms or species in the rates of DNA repair or the possible functional conservation of specific regions in a sequence. (In the case of nucleotide sequences, the molecular clock hypothesis in its most basic form also discounts the difference in acceptance rates between silent mutations that do not alter the meaning of a given codon and other mutations that result in a different amino acid being incorporated into the protein.) More statistically accurate methods allow the evolutionary rate on each branch of the phylogenetic tree to vary, thus producing better estimates of coalescence times for genes.
=== Sequence motifs ===
Frequently the primary structure encodes motifs that are of functional importance. Some examples of sequence motifs are: the C/D
and H/ACA boxes
of snoRNAs, Sm binding site found in spliceosomal RNAs such as U1, U2, U4, U5, U6, U12 and U3, the Shine-Dalgarno sequence,
the Kozak consensus sequence
and the RNA polymerase III terminator.
=== Sequence entropy ===
In bioinformatics, a sequence entropy, also known as sequence complexity or information profile, is a numerical sequence providing a quantitative measure of the local complexity of a DNA sequence, independently of the direction of processing. The manipulations of the information profiles enable the analysis of the sequences using alignment-free techniques, such as for example in motif and rearrangements detection.
== See also ==
Gene structure
Nucleic acid structure determination
Quaternary numeral system
Single-nucleotide polymorphism (SNP)
== References ==
== External links ==
A bibliography on features, patterns, correlations in DNA and protein texts | Wikipedia/DNA_sequences |
In molecular cloning, a vector is any particle (e.g., plasmids, cosmids, Lambda phages) used as a vehicle to artificially carry a foreign nucleic sequence – usually DNA – into another cell, where it can be replicated and/or expressed. A vector containing foreign DNA is termed recombinant DNA. The four major types of vectors are plasmids, viral vectors, cosmids, and artificial chromosomes. Of these, the most commonly used vectors are plasmids. Common to all engineered vectors are an origin of replication, a multicloning site, and a selectable marker.
The vector itself generally carries a DNA sequence that consists of an insert (in this case the transgene) and a larger sequence that serves as the "backbone" of the vector. The purpose of a vector which transfers genetic information to another cell is typically to isolate, multiply, or express the insert in the target cell. All vectors may be used for cloning and are therefore cloning vectors, but there are also vectors designed specially for cloning, while others may be designed specifically for other purposes, such as transcription and protein expression. Vectors designed specifically for the expression of the transgene in the target cell are called expression vectors, and generally have a promoter sequence that drives expression of the transgene. Simpler vectors called transcription vectors are only capable of being transcribed but not translated: they can be replicated in a target cell but not expressed, unlike expression vectors. Transcription vectors are used to amplify their insert.
The manipulation of DNA is normally conducted on E. coli vectors, which contain elements necessary for their maintenance in E. coli. However, vectors may also have elements that allow them to be maintained in another organism such as yeast, plant or mammalian cells, and these vectors are called shuttle vectors. Such vectors have bacterial or viral elements which may be transferred to the non-bacterial host organism, however other vectors termed intragenic vectors have also been developed to avoid the transfer of any genetic material from an alien species.
Insertion of a vector into the target cell is usually called transformation for bacterial cells, transfection for eukaryotic cells, although insertion of a viral vector is often called transduction.
== Characteristics ==
=== Plasmids ===
Plasmids are double-stranded extra chromosomal and generally circular DNA sequences that are capable of replication using the host cell's replication machinery. Plasmid vectors minimalistically consist of an origin of replication that allows for semi-independent replication of the plasmid in the host. Plasmids are found widely in many bacteria, for example in Escherichia coli, but may also be found in a few eukaryotes, for example in yeast such as Saccharomyces cerevisiae. Bacterial plasmids may be conjugative/transmissible and non-conjugative:
conjugative - mediate DNA transfer through conjugation and therefore spread rapidly among the bacterial cells of a population; e.g., F plasmid, many R and some col plasmids.
nonconjugative - do not mediate DNA through conjugation, e.g., many R and col plasmids.
Plasmids with specially-constructed features are commonly used in laboratory for cloning purposes. These plasmid are generally non-conjugative but may have many more features, notably a "multiple cloning site" where multiple restriction enzyme cleavage sites allow for the insertion of a transgene insert. The bacteria containing the plasmids can generate millions of copies of the vector within the bacteria in hours, and the amplified vectors can be extracted from the bacteria for further manipulation. Plasmids may be used specifically as transcription vectors and such plasmids may lack crucial sequences for protein expression. Plasmids used for protein expression, called expression vectors, would include elements for translation of protein, such as a ribosome binding site, start and stop codons.
=== Viral vectors ===
Viral vectors are genetically engineered viruses carrying modified viral DNA or RNA that has been rendered noninfectious, but still contain viral promoters and the transgene, thus allowing for translation of the transgene through a viral promoter. However, because viral vectors frequently lack infectious sequences, they require helper viruses or packaging lines for large-scale transfection. Viral vectors are often designed to permanently incorporate the insert into the host genome, and thus leave distinct genetic markers in the host genome after incorporating the transgene. For example, retroviruses leaves a characteristic retroviral integration pattern after insertion that is detectable and indicates that the viral vector has incorporated into the host genome.
=== Artificial chromosomes ===
Artificial chromosomes are manufactured chromosomes in the context of yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), or human artificial chromosomes (HACs). An artificial chromosome can carry a much larger DNA fragment than other vectors. YACs and BACs can carry a DNA fragment up to 300,000 nucleotides long. Three structural necessities of an artificial chromosome include an origin of replication, a centromere, and telomeric end sequences.
== Transcription ==
Transcription of the cloned gene is a necessary component of the vector when expression of the gene is required: one gene may be amplified through transcription to generate multiple copies of mRNAs, the template on which protein may be produced through translation. A larger number of mRNAs would express a greater amount of protein, and how many copies of mRNA are generated depends on the promoter used in the vector. The expression may be constitutive, meaning that the protein is produced constantly in the background, or it may be inducible whereby the protein is expressed only under certain condition, for example when a chemical inducer is added. These two different types of expression depend on the types of promoter and operator used.
Viral promoters are often used for constitutive expression in plasmids and in viral vectors because they normally force constant transcription in many cell lines and types reliably. Inducible expression depends on promoters that respond to the induction conditions: for example, the murine mammary tumor virus promoter only initiates transcription after dexamethasone application and the Drosophila heat shock promoter only initiates after high temperatures.
Some vectors are designed for transcription only, for example for in vitro mRNA production. These vectors are called transcription vectors. They may lack the sequences necessary for polyadenylation and termination, therefore may not be used for protein production.
== Expression ==
Expression vectors produce proteins through the transcription of the vector's insert followed by translation of the mRNA produced, they therefore require more components than the simpler transcription-only vectors. Expression in different host organism would require different elements, although they share similar requirements, for example a promoter for initiation of transcription, a ribosomal binding site for translation initiation, and termination signals.
=== Prokaryotes expression vector ===
Promoter - commonly used inducible promoters are promoters derived from lac operon and the T7 promoter. Other strong promoters used include Trp promoter and Tac-Promoter, which are a hybrid of both the Trp and Lac Operon promoters.
Ribosome binding site (RBS) - follows the promoter, and promotes efficient translation of the protein of interest.
Translation initiation site - Shine-Dalgarno sequence enclosed in the RBS, 8 base-pairs upstream of the AUG start codon.
=== Eukaryotes expression vector ===
Eukaryote expression vectors require sequences that encode for:
Polyadenylation tail: Creates a polyadenylation tail at the end of the transcribed pre-mRNA that protects the mRNA from exonucleases and ensures transcriptional and translational termination: stabilizes mRNA production.
Minimal UTR length: UTRs contain specific characteristics that may impede transcription or translation, and thus the shortest UTRs or none at all are encoded for in optimal expression vectors.
Kozak sequence: Vectors should encode for a Kozak sequence in the mRNA, which assembles the ribosome for translation of the mRNA.
== Features ==
Modern artificially-constructed vectors contain essential components found in all vectors, and may contain other additional features found only in some vectors:
Origin of replication: Necessary for the replication and maintenance of the vector in the host cell.
Promoter: Promoters are used to drive the transcription of the vector's transgene as well as the other genes in the vector such as the antibiotic resistance gene. Some cloning vectors need not have a promoter for the cloned insert but it is an essential component of expression vectors so that the cloned product may be expressed.
Cloning site: This may be a multiple cloning site or other features that allow for the insertion of foreign DNA into the vector through ligation.
Genetic markers: Genetic markers for viral vectors allow for confirmation that the vector has integrated with the host genomic DNA.
Antibiotic resistance: Vectors with antibiotic-resistance open reading frames allow for survival of cells that have taken up the vector in growth media containing antibiotics through antibiotic selection.
Epitope: Some vectors may contain a sequence for a specific epitope that can be incorporated into the expressed protein. It allows for antibody identification of cells expressing the target protein.
Reporter genes: Some vectors may contain a reporter gene that allow for identification of plasmid that contains inserted DNA sequence. An example is lacZ-α which codes for the N-terminus fragment of β-galactosidase, an enzyme that digests galactose. A multiple cloning site is located within lacZ-α, and an insert successfully ligated into the vector will disrupt the gene sequence, resulting in an inactive β-galactosidase. Cells containing vector with an insert may be identified using blue/white selection by growing cells in media containing an analogue of galactose (X-gal). Cells expressing β-galactosidase (therefore does not contain an insert) appear as blue colonies. White colonies would be selected as those that may contain an insert. Other commonly used reporters include green fluorescent protein and luciferase.
Targeting sequence: Expression vectors may include encoding for a targeting sequence in the finished protein that directs the expressed protein to a specific organelle in the cell or specific location such as the periplasmic space of bacteria.
Protein purification tags: Some expression vectors include proteins or peptide sequences that allows for easier purification of the expressed protein. Examples include polyhistidine-tag, glutathione-S-transferase, and maltose binding protein. Some of these tags may also allow for increased solubility of the target protein. The target protein is fused to the protein tag, but a protease cleavage site positioned in the polypeptide linker region between the protein and the tag allows the tag to be removed later.
== See also ==
Plasmid
Viral vector
Cloning vector
Expression vector
Hybrid vector
Minicircle
Recombinant DNA
Naked DNA
Vector (epidemiology), an organism that transmits disease
Human artificial chromosomes
Yeast artificial chromosomes
Bacterial artificial chromosomes
DNA vaccination
== References ==
== Further reading ==
== External links ==
Waksman Scholars introduction to vectors Archived 2008-01-18 at the Wayback Machine
A comparison of vectors in use for clinical gene transfer
Gene Transport Unit Archived 2007-12-06 at the Wayback Machine | Wikipedia/Vector_DNA |
Repeated sequences (also known as repetitive elements, repeating units or repeats) are short or long patterns that occur in multiple copies throughout the genome. In many organisms, a significant fraction of the genomic DNA is repetitive, with over two-thirds of the sequence consisting of repetitive elements in humans. Some of these repeated sequences are necessary for maintaining important genome structures such as telomeres or centromeres.
Repeated sequences are categorized into different classes depending on features such as structure, length, location, origin, and mode of multiplication. The disposition of repetitive elements throughout the genome can consist either in directly adjacent arrays called tandem repeats or in repeats dispersed throughout the genome called interspersed repeats. Tandem repeats and interspersed repeats are further categorized into subclasses based on the length of the repeated sequence and/or the mode of multiplication.
While some repeated DNA sequences are important for cellular functioning and genome maintenance, other repetitive sequences can be harmful. Many repetitive DNA sequences have been linked to human diseases such as Huntington's disease and Friedreich's ataxia. Some repetitive elements are neutral and occur when there is an absence of selection for specific sequences depending on how transposition or crossing over occurs. However, an abundance of neutral repeats can still influence genome evolution as they accumulate over time. Overall, repeated sequences are an important area of focus because they can provide insight into human diseases and genome evolution.
== History ==
In the 1950s, Barbara McClintock first observed DNA transposition and illustrated the functions of the centromere and telomere at the Cold Spring Harbor Symposium. McClintock's work set the stage for the discovery of repeated sequences because transposition, centromere structure, and telomere structure are all possible through repetitive elements, yet this was not fully understood at the time. The term "repeated sequence" was first used by Roy John Britten and D. E. Kohne in 1968; they found out that more than half of the eukaryotic genomes were repetitive DNA through their experiments on reassociation of DNA. Although the repetitive DNA sequences were conserved and ubiquitous, their biological role was yet unknown. In the 1990s, more research was conducted to elucidate the evolutionary dynamics of minisatellite and microsatellite repeats because of their importance in DNA-based forensics and molecular ecology. DNA-dispersed repeats were increasingly recognized as a potential source of genetic variation and regulation. Discoveries of deleterious repetitive DNA-related diseases stimulated further interest in this area of study. In the 2000s, the data from full eukaryotic genome sequencing enabled the identification of different promoters, enhancers, and regulatory RNAs which are all coded by repetitive regions. Today, the structural and regulatory roles of repetitive DNA sequences remain an active area of research.
== Types and functions ==
Many repeat sequences are likely to be non-functional, decaying remnants of Transposable elements, these have been labelled "junk" or "selfish" DNA. Nevertheless, occasionally some repeats may be exapted for other functions.
=== Tandem repeats ===
Tandem repeats are repeated sequences which are directly adjacent to each other in the genome. Tandem repeats may vary in the number of nucleotides comprising the repeated sequence, as well as the number of times the sequence repeats. When the repeating sequence is only 2–10 nucleotides long, the repeat is referred to as a short tandem repeat (STR) or microsatellite. When the repeating sequence is 10–60 nucleotides long, the repeat is referred to as a minisatellite. For minisatellites and microsatellites, the number of times the sequence repeats at a single locus can range from twice to hundreds of times.
Tandem repeats have a wide variety of biological functions in the genome. For example, minisatellites are often hotspots of meiotic homologous recombination in eukaryotic organisms. Recombination is when two homologous chromosomes align, break, and rejoin to swap pieces. Recombination is important as a source of genetic diversity, as a mechanism for repairing damaged DNA, and a necessary step in the appropriate segregation of chromosomes in meiosis. The presence of repeated sequence DNA makes it easier for areas of homology to align, thereby controlling when and where recombination occurs.
In addition to playing an important role in recombination, tandem repeats also play important structural roles in the genome. For example, telomeres are composed mainly of tandem TTAGGG repeats. These repeats fold into highly organized G quadruplex structures which protect the ends of chromosomal DNA from degradation. Repetitive elements are enriched in the middle of chromosomes as well. Centromeres are the highly compact regions of chromosomes which join sister chromatids together and also allow the mitotic spindle to attach and separate sister chromatids during cell division. Centromeres are composed of a 177 base pair tandem repeat named the α-satellite repeat. Pericentromeric heterochromatin, the DNA which surrounds the centromere and is important for structural maintenance, is composed of a mixture of different satellite subfamilies including the α-, β- and γ-satellites as well as HSATII, HSATIII, and sn5 repeats.
Some repetitive sequences, such as those with structural roles discussed above, play roles necessary for proper biological functioning. Other tandem repeats have deleterious roles which drive diseases. Many other tandem repeats, however, have unknown or poorly understood functions.
=== Interspersed repeats ===
Interspersed repeats are identical or similar DNA sequences which are found in different locations throughout the genome. Interspersed repeats are distinguished from tandem repeats in that the repeated sequences are not directly adjacent to each other but instead may be scattered among different chromosomes or far apart on the same chromosome. Most interspersed repeats are transposable elements (TEs), mobile sequences which can be "cut and pasted" or "copied and pasted" into different places in the genome. TEs were originally called "jumping genes" for their ability to move, yet this term is somewhat misleading as not all TEs are discrete genes.
Transposable elements that are transcribed into RNA, reverse-transcribed into DNA, then reintegrated into the genome are called retrotransposons. Just as tandem repeats are further subcategorized based on the length of the repeating sequence, there are many different types of retrotransposons. Long interspersed nuclear elements (LINEs) are typically 3–7 kilobases in length. Short interspersed nuclear elements (SINEs) are typically 100-300 base pairs and no longer than 600 base pairs. Long-terminal repeat retrotransposons (LTRs) are a third major class of retrotransposons and are characterized by highly repetitive sequences as the ends of the repeat. When a transposable element does not proceed through RNA as an intermediate, it is called a DNA transposon. Other classification systems refer to retrotransposons as "Class I" and DNA transposons as "Class II" transposable elements.
Transposable elements are estimated to constitute 45% of the human genome. Since uncontrolled propagation of TEs could wreak havoc on the genome, many regulatory mechanisms have evolved to silence their spread, including DNA methylation, histone modifications, non-coding RNAs (ncRNAs) including small interfering RNA (siRNA), chromatin remodelers, histone variants, and other epigenetic factors. However, TEs play a wide variety of important biological functions. When TEs are introduced into a new host, such as from a virus, they increase genetic diversity. In some cases, host organisms find new functions for the proteins which arise from expressing TEs in an evolutionary process called TE exaptation. Recent research also suggests that TEs serve to maintain higher-order chromatin structure and 3D genome organization. Furthermore, TEs contribute to regulating the expression of other genes by serving as distal enhancers and transcription factor binding sites.
The prevalence of interspersed elements in the genome has garnered attention for more research on their origins and functions. Some specific interspersed elements have been characterized, such as the Alu repeat and LINE1.
=== Intrachromosomal recombination ===
Homologous recombination between chromosomal repeated sequences in somatic cells of Nicotiana tabacum was found to be increased by exposure to mitomycin C, a bifunctional alkylating agent that crosslinks DNA strands. This increase in recombination was attributed to increased intrachromosomal recombinational repair. By this process, mitomycin C damaged DNA in one sequence is repaired using intact information from the other repeated sequence.
=== Direct and inverted repeats ===
While tandem and interspersed repeats are distinguished based on their location in the genome, direct and inverted repeats are distinguished based on the ordering of the nucleotide bases. Direct repeats occur when a nucleotide sequence is repeated with the same directionality. Inverted repeats occur when a nucleotide sequence is repeated in the inverse direction. For example, a direct repeat of "CATCAT" would be another repetition of "CATCAT". In contrast, the inverted repeated would be "ATGATG". When there are no nucleotides separating the inverted repeat, such as "CATCATATGATG", the sequence is called a palindromic repeat. Inverted repeats can play structural roles in DNA and RNA by forming stem loops and cruciforms.
== Evolutionary emergence of meiosis ==
The evolutionary origin of meiotic sexual reproduction is regarded as a long-standing evolutionary enigma. In prokaryotes, lateral gene transfer emerged as an early evolved form of sexual interaction. However, repeat sequences in prokaryotic DNA limit the effectiveness of lateral gene transfer at purging deleterious mutations, as well as limiting the accurate repair of DNA damages by homologous recombination. Colnoghi et al. proposed that such constraints on the beneficial effects of sexual interaction in prokaryotes favored the evolution of meiotic sex and thus the emergence of eukaryotes. It was concluded that the transition to homologous pairing along linear chromosomes that occurs during meiosis was the crucial innovation in meiotic sexual reproduction, and this innovation was instrumental in the evolutionary expansion of eukaryotic genomes that facilitated increased functional and morphological complexity.
== Repeated sequences in human disease ==
For humans, some repeated DNA sequences are associated with diseases. Specifically, tandem repeat sequences, underlie several human disease conditions, particularly trinucleotide repeat diseases such as Huntington's disease, fragile X syndrome, several spinocerebellar ataxias, myotonic dystrophy and Friedreich's ataxia. Trinucleotide repeat expansions in the germline over successive generations can lead to increasingly severe manifestations of the disease. These trinucleotide repeat expansions may occur through strand slippage during DNA replication or during DNA repair synthesis. It has been noted that genes containing pathogenic CAG repeats often encode proteins that themselves have a role in the DNA damage response and that repeat expansions may impair specific DNA repair pathways. Faulty repair of DNA damages in repeat sequences may cause further expansion of these sequences, thus setting up a vicious cycle of pathology.
=== Huntington's disease ===
Huntington's disease is a neurodegenerative disorder which is due to the expansion of repeated trinucleotide sequence CAG in exon 1 of the huntingtin gene (HTT). This gene is responsible for encoding the protein huntingtin which plays a role in preventing apoptosis, otherwise known as cell death, and repair of oxidative DNA damage. In Huntington's disease the expansion of the trinucleotide sequence CAG encodes for a mutant huntingtin protein with an expanded polyglutamine domain. This domain causes the protein to form aggregates in nerve cells preventing normal cellular function and resulting in neurodegeneration.
=== Fragile X syndrome ===
Fragile X syndrome is caused by the expansion of the DNA sequence CCG in the FMR1 gene on the X chromosome. This gene produces the RNA-binding protein FMRP. In the case of Fragile X syndrome the repeated sequence makes the gene unstable and therefore silences the gene FMR1. Because the gene resides on the X chromosome, females who have two X chromosomes are less effected than males who only have on X chromosome and one Y chromosome because the second X chromosome can compensate for the silencing of the gene on the other X chromosome.
=== Spinocerebellar ataxias ===
The disease spinocerebellar ataxias has CAG trinucleotide repeat sequences that underlie several types of spinocerebellar ataxias (SCAs-SCA1; SCA2; SCA3; SCA6; SCA7; SCA12; SCA17). Similar to Huntington's disease, the polyglutamine tail created due to this trinucleotide expansion causes aggregation of proteins, preventing normal cellular function and causing neurodegeneration.
=== Friedreich's Ataxia ===
Friedreich's ataxia is a type of ataxia that has an expanded repeat sequence GAA in the frataxin gene. The frataxin gene is responsible for producing the frataxin protein, which is a mitochondrial protein involved in energy production and cellular respiration. The expanded GAA sequence results in the silencing of the first intron resulting in loss of function in the frataxin protein. The loss of a functional FXN gene leads to issues with mitochondrial functioning as a whole and can present phenotypically in patients as difficulty walking.
=== Myotonic dystrophy ===
Myotonic dystrophy is a disorder that presents as muscle weakness and consists of two main types: DM1 and DM2. Both types of myotonic dystrophy are due to expanded DNA sequences. In DM1 the DNA sequence that is expanded is CTG while in DM2 it is CCTG. These two sequences are found on different genes with the expanded sequence in DM2 being found on the ZNF9 gene and the expanded sequence in DM1 found on the DMPK gene. The two genes don't encode for proteins unlike other disorders like Huntington's disease or Fragile X syndrome. It has been shown, however, that there is a link between RNA toxicity and the repeat sequences in DM1 and DM2.
=== Amyotrophic lateral sclerosis and Frontotemporal dementia ===
Not all diseases caused by repeated DNA sequences are trinucleotide repeat diseases. The diseases amyotrophic lateral sclerosis and frontotemporal dementia are caused by hexanucleotide GGGGCC repeat sequences in the C9orf72 gene, causing RNA toxicity that leads to neurodegeneration.
== Biotechnology ==
Repetitive DNA is hard to sequence using next-generation sequencing techniques because sequence assembly from short reads simply cannot determine the length of a repetitive part. This issue is particularly serious for microsatellites, which are made of tiny 1-6bp repeat units. Although they are difficult to sequence, these short repeats have great value in DNA fingerprinting and evolutionary studies. Many researchers have historically left out repetitive sequences when analyzing and publishing whole genome data due to technical limitations.
Bustos. et al. proposed one method of sequencing long stretches of repetitive DNA. The method combines the use of a linear vector for stabilization and exonuclease III for deletion of continuing simple sequence repeats (SSRs) rich regions. First, SSR-rich fragments are cloned into a linear vector that can stably incorporate tandem repeats up to 30kb. Expression of repeats is prohibited by the transcriptional terminators in the vector. The second step involves the use of exonuclease III. The enzyme can delete nucleotide at the 3' end which results in the production of a unidirectional deletion of SSR fragments. Finally, this product which has deleted fragments is multiplied and analyzed with colony PCR. The sequence is then built by an ordered sequencing of a set of clones containing different deletions.
== See also ==
== References ==
== External links ==
Function of Repetitive DNA
DNA+Repetitious+Region at the U.S. National Library of Medicine Medical Subject Headings (MeSH) | Wikipedia/Repetitive_DNA |
Transmission electron microscopy DNA sequencing is a single-molecule sequencing technology that uses transmission electron microscopy techniques. The method was conceived and developed in the 1960s and 70s, but lost favor when the extent of damage to the sample was recognized.
In order for DNA to be clearly visualized under an electron microscope, it must be labeled with heavy atoms. In addition, specialized imaging techniques and aberration corrected optics are beneficial for obtaining the resolution required to image the labeled DNA molecule. In theory, transmission electron microscopy DNA sequencing could provide extremely long read lengths, but the issue of electron beam damage may still remain and the technology has not yet been commercially developed.
== History ==
Only a few years after James Watson and Francis Crick deduced the structure of DNA, and nearly two decades before Frederick Sanger published the first method for rapid DNA sequencing, Richard Feynman, an American physicist, envisioned the electron microscope as the tool that would one day allow biologists to "see the order of bases in the DNA chain". Feynman believed that if the electron microscope could be made powerful enough, then it would become possible to visualize the atomic structure of any and all chemical compounds, including DNA.
In 1970, Albert Crewe developed the high-angle annular dark-field imaging (HAADF) imaging technique in a scanning transmission electron microscope. Using this technique, he visualized individual heavy atoms on thin amorphous carbon films. In 2010 Krivanek and colleagues reported several technical improvements to the HAADF method, including a combination of aberration corrected electron optics and low accelerating voltage. The latter is crucial for imaging biological objects, as it allows to reduce damage by the beam and increase the image contrast for light atoms. As a result, single atom substitutions in a boron nitride monolayer could be imaged.
Despite the invention of a multitude of chemical and fluorescent sequencing technologies, electron microscopy is still being explored as a means of performing single-molecule DNA sequencing. For example, in 2012 a collaboration between scientists at Harvard University, the University of New Hampshire and ZS Genetics demonstrated the ability to read long sequences of DNA using the technique, however transmission electron microscopy DNA sequencing technology is still far from being commercially available.
== Principle ==
The electron microscope has the capacity to obtain a resolution of up to 100 pm, whereby microscopic biomolecules and structures such as viruses, ribosomes, proteins, lipids, small molecules and even single atoms can be observed.
Although DNA is visible when observed with the electron microscope, the resolution of the image obtained is not high enough to allow for deciphering the sequence of the individual bases, i.e., DNA sequencing. However, upon differential labeling of the DNA bases with heavy atoms or metals, it is possible to both visualize and distinguish between the individual bases. Therefore, electron microscopy in conjunction with differential heavy atom DNA labeling could be used to directly image the DNA in order to determine its sequence.
== Workflow ==
=== Step 1 – DNA denaturation ===
As in a standard polymerase chain reaction (PCR), the double stranded DNA molecules to be sequenced must be denatured before the second strand can be synthesized with labeled nucleotides.
=== Step 2 – Heavy atom labeling ===
The elements that make up biological molecules (C, H, N, O, P, S) are too light (low atomic number, Z) to be clearly visualized as individual atoms by transmission electron microscopy. To circumvent this problem, the DNA bases can be labeled with heavier atoms (higher Z). Each nucleotide is tagged with a characteristic heavy label, so that they can be distinguished in the transmission electron micrograph.
ZS Genetics proposes using three heavy labels: bromine (Z=35), iodine (Z=53), and trichloromethane (total Z=63). These would appear as differential dark and light spots on the micrograph, and the fourth DNA base would remain unlabeled.
Halcyon Molecular, in collaboration with the Toste group, proposes that purine and pyrimidine bases can be functionalized with platinum diamine or osmium tetraoxide bipyridine, respectively. Heavy metal atoms such as osmium (Z=76), iridium (Z=77), gold (Z=79), or uranium (Z=92) can then form metal-metal bonds with these functional groups to label the individual bases.
=== Step 3 – DNA alignment on substrate ===
The DNA molecules must be stretched out on a thin, solid substrate so that order of the labeled bases will be clearly visible on the electron micrograph. Molecular combing is a technique that utilizes the force of a receding air-water interface to extend DNA molecules, leaving them irreversibly bound to a silane layer once dry. This is one means by which alignment of the DNA on a solid substrate may be achieved.
=== Step 4 – TEM imaging ===
Transmission electron microscopy (TEM) produces high magnification, high resolution images by passing a beam of electrons through a very thin sample. Whereas atomic resolution has been demonstrated with conventional TEM, further improvement in spatial resolution requires correcting the spherical and chromatic aberrations of the microscope lenses. This has only been possible in scanning transmission electron microscopy where the image is obtained by scanning the object with a finely focused electron beam, in a way similar to a cathode ray tube. However, the achieved improvement in resolution comes together with irradiation of the studied object by much higher beam intensities, the concomitant sample damage and the associated imaging artefacts. Different imaging techniques are applied depending on whether the sample contains heavy or light atoms:
Annular dark-field imaging measures the scattering of electrons as they deflect off the nuclei of the atoms in the transmission electron microscopy sample. This is best suited to samples containing heavy atoms, as they cause more scattering of electrons. The technique has been used to image atoms as light as boron, nitrogen, and carbon; however, the signal is very weak for such light atoms. If annular dark-field microscopy is put to use for transmission electron microscopy DNA sequencing, it will certainly be necessary to label the DNA bases with heavy atoms so that a strong signal can be detected.
Annular bright-field imaging detects electrons transmitted directly through the sample, and measures the wave interference produced by their interactions with the atomic nuclei. This technique can detect light atoms with greater sensitivity than annular dark-field imaging methods. In fact, oxygen, nitrogen, lithium, and hydrogen in crystalline solids have been imaged using annular bright-field electron microscopy. Thus, it is theoretically possible to obtain direct images of the atoms in the DNA chain; however, the structure of DNA is much less geometric than crystalline solids, so direct imaging without prior labeling may not be achievable.
=== Step 5 – Data analysis ===
Dark and bright spots on the electron micrograph, corresponding to the differentially labeled DNA bases, are analyzed by computer software.
== Applications ==
Transmission electron microscopy DNA sequencing is not yet commercially available, but the long read lengths that this technology may one day provide will make it useful in a variety of contexts.
=== De novo genome assembly ===
When sequencing a genome, it must be broken down into pieces that are short enough to be sequenced in a single read. These reads must then be put back together like a jigsaw puzzle by aligning the regions that overlap between reads; this process is called de novo genome assembly. The longer the read length that a sequencing platform provides, the longer the overlapping regions, and the easier it is to assemble the genome. From a computational perspective, microfluidic Sanger sequencing is still the most effective way to sequence and assemble genomes for which no reference genome sequence exists. The relatively long read lengths provide substantial overlap between individual sequencing reads, which allows for greater statistical confidence in the assembly. In addition, long Sanger reads are able to span most regions of repetitive DNA sequence which otherwise confound sequence assembly by causing false alignments. However, de novo genome assembly by Sanger sequencing is extremely expensive and time-consuming. Second generation sequencing technologies, while less expensive, are generally unfit for de novo genome assembly due to short read lengths. In general, third generation sequencing technologies, including transmission electron microscopy DNA sequencing, aim to improve read length while maintaining low sequencing cost. Thus, as third generation sequencing technologies improve, rapid and inexpensive de novo genome assembly will become a reality.
=== Full haplotypes ===
A haplotype is a series of linked alleles that are inherited together on a single chromosome. DNA sequencing can be used to genotype all of the single nucleotide polymorphisms (SNPs) that constitute a haplotype. However, short DNA sequencing reads often cannot be phased; that is, heterozygous variants cannot be confidently assigned to the correct haplotype. In fact, haplotyping with short read DNA sequencing data requires very high coverage (average >50x coverage of each DNA base) to accurately identify SNPs, as well as additional sequence data from the parents so that Mendelian transmission can be used to estimate the haplotypes. Sequencing technologies that generate long reads, including transmission electron microscopy DNA sequencing, can capture entire haploblocks in a single read. That is, haplotypes are not broken up among multiple reads, and the genetically linked alleles remain together in the sequencing data. Therefore, long reads make haplotyping easier and more accurate, which is beneficial to the field of population genetics.
=== Copy number variants ===
Genes are normally present in two copies in the diploid human genome; genes that deviate from this standard copy number are referred to as copy number variants (CNVs). Copy number variation can be benign (these are usually common variants, called copy number polymorphisms) or pathogenic. CNVs are detected by fluorescence in situ hybridization (FISH) or comparative genomic hybridization (CGH). To detect the specific breakpoints at which a deletion occurs, or to detect genomic lesions introduced by a duplication or amplification event, CGH can be performed using a tiling array (array CGH), or the variant region can be sequenced. Long sequencing reads are especially useful for analyzing duplications or amplifications, as it is possible to analyze the orientation of the amplified segments if they are captured in a single sequencing read.
=== Cancer ===
Cancer genomics, or oncogenomics, is an emerging field in which high-throughput, second generation DNA sequencing technology is being applied to sequence entire cancer genomes. Analyzing this short read sequencing data encompasses all of the problems associated with de novo genome assembly using short read data. Furthermore, cancer genomes are often aneuploid. These aberrations, which are essentially large scale copy number variants, can be analyzed by second-generation sequencing technologies using read frequency to estimate the copy number. Longer reads would, however, provide a more accurate picture of copy number, orientation of amplified regions, and SNPs present in cancer genomes.
=== Microbiome sequencing ===
The microbiome refers the total collection of microbes present in a microenvironment and their respective genomes. For example, an estimated 100 trillion microbial cells colonize the human body at any given time. The human microbiome is of particular interest, as these commensal bacteria are important for human health and immunity. Most of the Earth's bacterial genomes have not yet been sequenced; undertaking a microbiome sequencing project would require extensive de novo genome assembly, a prospect which is daunting with short read DNA sequencing technologies. Longer reads would greatly facilitate the assembly of new microbial genomes.
== Strengths and weaknesses ==
Compared to other second- and third-generation DNA sequencing technologies, transmission electron microscopy DNA sequencing has a number of potential key strengths and weaknesses, which will ultimately determine its usefulness and prominence as a future DNA sequencing technology.
=== Strengths ===
Longer read lengths: ZS Genetics has estimated potential read lengths of transmission electron microscopy DNA sequencing to be 10,000 to 20,000 base pairs with a rate of 1.7 billion base pairs per day. Such long read lengths would allow easier de novo genome assembly and direct detection of haplotypes, among other applications.
Lower cost: Transmission electron microscopy DNA sequencing is estimated to cost just US$5,000-US$10,000 per human genome, compared to the more expensive second-generation DNA sequencing alternatives.
No dephasing: Dephasing of the DNA strands due to loss in synchronicity during synthesis is a major problem of second-generation sequencing technologies. For transmission electron microscopy DNA sequencing and several other third-generation sequencing technologies, synchronization of the reads is unnecessary as only one molecule is being read at a time.
Shorter turnaround time: The capacity to read native fragments of DNA renders complex template preparation an unnecessary step in the general workflow of whole genome sequencing. Consequently, shorter turnaround times are possible.
=== Weaknesses ===
High capital cost: A transmission electron microscope with sufficient resolution required for transmission electron microscopy DNA sequencing costs approximately US$1,000,000, therefore pursuing DNA sequencing by this method requires a substantial investment.
Technically challenging: Selective heavy atom labeling and attaching and straightening the labeled DNA to a substrate are a serious technical challenge. Further, the DNA sample should be stable to the high vacuum of electron microscope and irradiation by a focused beam of high-energy electrons.
Potential PCR bias and artefacts: Although PCR is only being utilized in transmission electron microscopy DNA sequencing as a means to label the DNA strand with heavy atoms or metals, there could be the possibility of introducing bias in template representation or errors during the single amplification.
=== Comparison to other sequencing technologies ===
Many non-Sanger second- and third-generation DNA sequencing technologies have been or are currently being developed with the common aim of increasing throughput and decreasing cost such that personalized genetic medicine can be fully realized.
Both the US$10 million Archon X Prize for Genomics supported by the X Prize Foundation (Santa Monica, CA, USA) and the US$70 million in grant awards supported by the National Human Genome Research Institute of the National Institutes of Health (NIH-NHGRI) are fueling the rapid burst of research activity in the development of new DNA sequencing technologies.
Since different approaches, techniques, and strategies are what define each DNA sequencing technology, each has its own strengths and weaknesses. Comparison of important parameters between various second- and third-generation DNA sequencing technologies are presented in Table 1.
== References == | Wikipedia/Transmission_electron_microscopy_DNA_sequencing |
Pacific Biosciences of California, Inc. (aka PacBio) is an American biotechnology company founded in 2004 that develops and manufactures systems for gene sequencing and some novel real time biological observation. PacBio has two principal sequencing platforms: single-molecule real-time sequencing (SMRT), based on the properties of zero-mode waveguides and sequencing by binding (SBB) chemistry, which uses native nucleotides and scarless incorporation for DNA binding and extension.
== History ==
The company was founded based on research done at Cornell University that combined semiconductor processing and photonics with biotechnology research. Three graduate students in the lab of Professors Watt W. Webb — Jonas Korlach — and Harold Craighead — Steve Turner and Mathieu Foquet — became the first employees.
It began under the name Nanofluidics, Inc. The company raised nearly US$400,000,000 in six rounds of primarily venture capital financing, making it one of the most capitalized startups in 2010 leading up to their public offering in October of that year. Key investors included Mohr Davidow Ventures, Kleiner, Perkins, Caufield & Byers, Alloy Ventures, and Wellcome Trust.
The company's first commercial product, the PacBio RS, was sold to a limited set of customers in 2010 and was commercially released in early 2011. A subsequent version of the sequencer called the PacBio RS II was released in April 2013.
=== Leadership ===
In 2004, Kleiner Perkins entrepreneur-in-residence Hugh Martin became CEO. On 6 January 2012 board member Michael Hunkapiller, PhD assumed the role of CEO. Hunkapiller retired in September 2020, and was replaced by chairman of the board Christian Henry. Henry was a former executive VP and chief commercial officer of Illumina before joining the board at PacBio in July 2018.
=== Illumina: attempted acquisition ===
On 1 November 2018, Illumina, Inc. agreed to purchase PacBio for US$1.2 billion in cash. The deal was expected to close in the fourth quarter of 2019. In December 2019, the Federal Trade Commission sued to block the acquisition. The deal was abandoned with an announcement on 2 January 2020. Illumina further agreed to pay Pacific Biosciences a $98 million US termination fee plus previously agreed upon deal extension payments of $22 million US in February and $6 million US in March 2020.
== Sequencing technology ==
=== Sequencing instruments ===
The company's first scientific instrument, called the PacBio RS, was released to a limited set of customers in late 2010., with full commercial release in early 2011. Sequencing provider GATC Biotech was selected by Pacific Biosciences as its first European service provider in late 2010. A new version of the sequencer was released in April 2013 it produced longer sequence reads and higher throughput than the original RS instrument. The RS instrument will officially be supported until the end of 2021. In September 2015, the company released a new sequencing instrument, the Sequel System, with increased sequencing capacity at a smaller size and lower price compared to the PacBio RS II. Subsequently, in October 2022, PacBio launched a new sequencing system, which can sequence 1,300 human genomes per year as compared to 86 per year of the previous PacBio sequencing machines.
=== Reagents and SMRT Cells ===
To use either instrument, customers must also purchase reagent packs for DNA preparation and sequencing and small consumables called "SMRT Cells." Cells for early forms of the sequencer are slightly less than one-centimeter square and contains tens of thousands of zero-mode waveguides, whereas newer systems have a higher density of cells and contain 25 million zero-mode waveguides (ZMWGs), allowing for faster DNA sequencing.
=== Software and applications ===
Their secondary analysis bioinformatics product for the RS, called “SMRT Analysis”, was open source. For the Sequel system the secondary analysis software was reorganized as the "SMRT Link" application. In 2013, the company released new bioinformatics tools for automated genome assembly (HGAP) and finishing (Quiver).
== External links ==
Company web site
Wall Street Journal profile
Business data for PacBio:
== References == | Wikipedia/Pacific_Biosciences |
DNA profiling is the determination of a DNA profile for legal and investigative purposes. DNA analysis methods have changed countless times over the years as technology changes and allows for more information to be determined with less starting material. Modern DNA analysis is based on the statistical calculation of the rarity of the produced profile within a population.
While most well known as a tool in forensic investigations, DNA profiling can also be used for non-forensic purposes such as paternity testing and human genealogy research.
== History ==
The methods for producing a DNA profile were developed by Alec Jeffreys and his team in 1985. Jefferys discovered that an unknown sample of DNA such as blood, hair, saliva, or semen could be analyzed and a unique DNA pattern/profile could be developed. A year after his discovery, Jefferys was asked to use his new found DNA analysis to convict a man that police believed was responsible for 2 rape murders. Jefferys proved that the man was innocent using DNA from the crime scene.
When DNA analysis was first discovered, a process called Restriction Fragment Length Polymorphism (RFLP) was used to analyze DNA. However, RFLP was an inefficient process due to the fact that it used up large amounts of DNA which could not always be obtained from a crime scene. Modern day technology has evolved beyond RFLP. Short Tandem Repeat (STR) analysis is the modern day equivalent of RFLP. Not only does STR analysis use less of a sample to analyze DNA, but it also is a part of a larger process called Polymerase Chain Reaction (PCR). PCR is a process that can be used to quickly reproduce up to a billion copies of a singular segment of DNA.
== Methods ==
=== Retired methods ===
==== RFLP analysis ====
The first true method of DNA profiling was restriction fragment length polymorphism analysis. The first use of RFLP analysis in forensic casework was in 1985 in the United Kingdom. This type of analysis used variable number tandem repeats (VNTRs) to distinguish between individuals. VNTRs are common throughout the genome and consist of the same DNA sequence repeated again and again. Different individuals can have a different number of repeats at a specific location in the genome. For example, person A could have 4 while person B could have 5 repeats. The differences were visualized through a process called gel electrophoresis. Smaller fragments would travel farther through the gel than larger fragments separating them out. These differences were used to distinguish between individuals and when multiple VNTR sites were run together, RFLP analysis has a high degree of individualizing power.
The process of RFLP analysis was extremely time consuming and due to the length of the repeats used, between 9 and 100 base pairs, amplification methods such as the polymerase chain reaction could not be used. This limited RFLP to samples that already had a larger quantity of DNA available to start with and did not perform well with degraded samples. RFLP analysis was the primary type of analysis performed in most forensic laboratories before finally being retired and replaced by newer methods. It was fully abandoned by the FBI in 2000 and replaced with STR analysis.
==== DQ alpha testing ====
Developed in 1991, DQ alpha testing was the first forensic DNA technique that utilized the polymerase chain reaction. This technique allowed for the use of far fewer cells than RFLP analysis making it more useful for crime scenes that did not have the large amounts of DNA material that was previously required. The DQ alpha 1 locus (or location) was also polymorphic and had multiple different alleles that could be used to limit the pool of individuals that could have produced that result and increasing the probability of exclusion.
The DQ alpha locus was combined with other loci in a commercially available kit called Polymarker in 1993. Polymarker was a precursor to modern multiplexing kits and allowed multiple different loci to be examined with one product. While more sensitive than RFLP analysis, Polymarker did not contain the same discriminatory power as the older RFLP testing. By 1995, scientists attempted to return to a VNTR based analysis combined with PCR technology called amplified fragment length polymorphisms (AmpFLP).
==== AmpFLP ====
AmpFLP was the first attempt to couple VNTR analysis with PCR for forensic casework. This method used shorter VNTRs than RFLP analysis, between 8 and 16 base pairs. The shorter base pair sizes of AmpFLP was designed to work better with the amplification process of PCR. It was hoped that this technique would allow for the discriminating power of RFLP analysis with the ability to process samples that have less template DNA to work with or which were otherwise degraded. However, only a few loci were validated for forensic applications to work with AmpFLP analysis as forensic labs quickly moved on to other techniques limited its discriminating ability for forensic samples.
The technique was ultimately never widely used although it is still in use in smaller countries due to its lower cost and simpler setup compared to newer methods. By the late 1990s, laboratories began switching over to newer methods including STR analysis. These used even shorter fragments of DNA and could more reliably be amplified using PCR while still maintaining, and improving, the discriminatory power of the older methods.
=== Current methods ===
==== STR analysis ====
Short tandem repeat (STR) analysis is the primary type of forensic DNA analysis performed in modern DNA laboratories. STR analysis builds upon RFLP and AmpFLP used in the past by shrinking the size of the repeat units, to 2 to 6 base pairs, and by combining multiple different loci into one PCR reaction. These multiplexing assay kits can produce allele values for dozens of different loci throughout the genome simultaneously limiting the amount of time it takes to gain a full, individualizing, profile. STR analysis has become the gold standard for DNA profiling and is used extensively in forensic applications.
STR analysis can also be restricted to just the Y chromosome. Y-STR analysis can be used in cases that involve paternity or in familial searching as the Y chromosome is identical down the paternal line (except in cases where a mutation occurred). Certain multiplexing kits combine both autosomal and Y-STR loci into one kit further reducing the amount of time it takes to obtain a large amount of data.
Currently, STR analysis requires multiple cells to create a full DNA profile. However, science is getting closer to creating a full DNA profile using STR analysis on single cells.
==== mtDNA sequencing ====
Mitochondrial DNA sequencing is a specialized technique that uses the separate mitochondrial DNA present in most cells. This DNA is passed down the maternal line and is not unique between individuals. However, because of the number of mitochondria present in cells, mtDNA analysis can be used for highly degraded samples or samples where STR analysis would not produce enough data to be useful. mtDNA is also present in locations where autosomal DNA would be absent, such as in the shafts of hair.
Because of the increased chance of contamination when dealing with mtDNA, few laboratories process mitochondrial samples. Those that do have specialized protocols in place that further separate different samples from each other to avoid cross-contamination.
==== Rapid DNA ====
Rapid DNA is a "swab in-profile out" technology that completely automates the entire DNA extraction, amplification, and analysis process. Rapid DNA instruments are able to go from a swab to a DNA profile in as little as 90 minutes and eliminates the need for trained scientists to perform the process. These instruments are being looked at for use in the offender booking process allowing police officers to obtain the DNA profile of the person under arrest.
Recently, the Rapid DNA Act of 2017 was passed in the United States, directing the FBI to create protocols for the implementation of this technology throughout the country. Currently, DNA obtained from these instruments is not eligible for upload to national DNA databases as they do not analyze enough loci to meet the standard threshold. However, multiple police agencies already use Rapid DNA instruments to collect samples from people arrested in their area. These local DNA database are not, subject to federal or state regulations.
==== Massively parallel sequencing ====
Also known as next-generation sequencing, massively parallel sequencing (MPS) builds upon STR analysis by introducing direct sequencing of the loci. Instead of the number of repeats present at each location, MPS would give the scientist the actual base pair sequence. Theoretically MPS has the ability to distinguish between identical twins as random point mutations would be seen within repeat segments that would not be picked up by traditional STR analysis.
== Profile rarity ==
When a DNA profile is used in an evidentiary manner a match statistic is provided that explains how rare a profile is within a population. Specifically, this statistic is the probability that a person picked randomly out of a population would have that specific DNA profile. It is not the probability that the profile "matches" someone. There are multiple different methods to determining this statistic and each are used by various laboratories based on their experience and preference. However, likelihood ratio calculations is becoming the preferred method over the other two most commonly used methods, random man not excluded and combined probability of inclusion. Match statistics are especially important in mixture interpretation where there is more than one contributor to a DNA profile. When these statistics are given in a courtroom setting or in a laboratory report they are usually given for the three most common races of that specific area. This is because the allele frequencies at different loci changed based on the individual's ancestry. https://strbase.nist.gov/training/6_Mixture-Statistics.pdf Archived 2022-08-15 at the Wayback Machine
=== Random man not excluded ===
The probability produced with this method is the probability that a person randomly selected out the population could not be excluded from the analyzed data. This type of match statistic is easy to explain in a courtroom setting to individuals who have no scientific background but it also loses a lot of discriminating power as it does not take into account the suspect's genotype. This approach is commonly used when the sample is degraded or contains so many contributors that a singular profile cannot be determined. It is also useful in explaining to laypersons as the method of obtaining the statistic is straightforward. However, due to its limited discriminating power, RMNE is not generally performed unless no other method can be used. RMNE is not recommended for use in data that indicates a mixture is present.
=== Combined probability of inclusion/exclusion ===
Combined probability of inclusion or exclusion calculates the probability that a random, unrelated, person would be a contributor to a DNA profile or DNA mixture. In this method, statistics for each individual locus is determined using population statistics and then combined to get the total CPI or CPE. These calculations are repeated for all available loci with all available data and then each value is multiplied together to get the total combined probability of inclusion or exclusion. Since the values are multiplied together, extremely small numbers can be achieved using CPI. CPI or CPE is considered an acceptable statistical calculation when a mixture is indicated. https://www.promega.com/-/media/files/resources/conference-proceedings/ishi-15/parentage-and-mixture-statistics-workshop/generalpopulationstats.pdf?la=en
==== Example calculation for single source profile ====
Probability of a Caucasian having a 14 allele at vWA = .10204
Probability of a Caucasian having a 17 allele at vWA = .26276
Probability of a Caucasian having either a 14 or a 17 allele (P) = .10204 + .26276 = .3648
Probability of any other alleles being present (Q) = 1 - P or 1 - .3648 = .6352
Probability of exclusion for vWA = Q2 + 2Q(1-Q) or .63522 + 2(.6352)(1 - .6352) = .86692096 ≈ 86.69%
Probability of inclusion for vWA = 1 - CPE or 1 - .86692096 = .13307904 ≈ 13.31%
==== Example calculation for mixture profile ====
Probability of a Caucasian having a 14 allele at vWA = .10204
Probability of a Caucasian having a 15 allele at vWA = .11224
Probability of a Caucasian having a 16 allele at vWA = .20153
Probability of a Caucasian having a 19 allele at vWA = .08418
Probability of a Caucasian having any of 14, 15, 16, or 19 alleles (P) = .10204 + .11224 + .20153 + .08418 = .49999
Probability of any other alleles being present (Q) = 1 - P or 1 - .49999 = .50001
Probability of exclusion for vWA = Q2 + 2Q(1-Q) or .500012 + 2(.50001)(1 - .50001) = .7500099999 ≈ 75%
Probability of inclusion for vWA = 1 - CPE or 1 - .7500099999 = .2499900001 ≈ 25%
=== Likelihood ratio ===
Likelihood ratios (LR) are a comparison of two different probabilities to determine which one is more likely. When it involves a trial the LR is the probability of the prosecution's argument versus the probability of the defense's argument given their starting assumptions. In this scenario the prosecution's probability is often equal to 1 since the assumption is that the prosecution would not prosecute a suspect unless they were absolutely certain (100%) that they have the right person. Likelihood ratios are becoming more common in laboratories due to their usefulness in presenting statistics for data that indicates multiple contributors as well as their use in probabilistic genotyping software that predicts the most likely allele combinations given a set of data.
The drawbacks with using likelihood ratios is that they are very difficult to understand how analysts arrived at a specific value and the mathematics involved get very complicated as more data is introduced to the equations. In order to combat these problems in a courtroom setting, some laboratories have set up a "verbal scale" that replaces the actual numeral value of the likelihood ratio.
== References == | Wikipedia/Forensic_DNA_analysis |
The Genographic Project, launched on 13 April 2005 by the National Geographic Society and IBM, was a genetic anthropological study (sales discontinued on 31 May 2019) that aimed to map historical human migrations patterns by collecting and analyzing DNA samples. The final phase of the project was Geno 2.0 Next Generation. Upon retirement of the site, 1,006,543 participants in over 140 countries had joined the project.
== Project history ==
=== Beginnings ===
Created and led by project director Spencer Wells in 2005, the Genographic Project was a privately funded, not-for-profit collaboration between the National Geographic Society, IBM and the Waitt Foundation. Field researchers at eleven regional centers around the world began by collecting DNA samples from indigenous populations. Since the fall of 2015, the Project was led by Miguel Vilar.
In fall 2012, the Genographic Project announced the completion of a new genotyping array, dedicated to genetic anthropology, called GenoChip. GenoChip is specifically designed for anthropological testing and includes SNPs from autosomal DNA, X-chromosome DNA, Y-chromosome DNA and mitochondrial DNA (mtDNA). The design of the new chip was a collaborative effort between Wells of National Geographic, Eran Elhaik of Johns Hopkins, Family Tree DNA, and Illumina.
In August of 2015, a new chip was designed as a joint effort between Vilar, Genographic Lead Scientist, and Family Tree DNA.
In the spring of 2019, it was announced that the Geno project had ended, but results would remain available online until 2020. In July 2020 the site was retired.
=== Geno 2.0 ===
The autosomal admixture analysis developed by Wells and Elhaik classifies individuals by assessing their proportions of genomic ancestry related to nine ancestral regions: Northeast Asian, Mediterranean, Southern African, Southwest Asian, Oceanian, Southeast Asian, Northern European, Sub-Saharan African and Native American.
== Geno 2.0 Next Generation ==
In 2016, the project began utilizing cutting-edge Helix DNA sequencing for Geno 2.0 Next Generation, the current phase of the Genographic Project. As compared to earlier phases which used nine regional affiliations, Geno 2.0 Next Generation analyzes modern-day indigenous populations around the world using either 18 or 22 regional affiliations. Utilizing a DNA-collection kit, Helix acquires a saliva sample from a participant, which is then analyzed for genomic identifiers that offer unprecedented insight into the person's genetic origins. The data is then uploaded to the Genographic Project DNA database.
== Volunteer participation ==
From 2005 to 2019 Genographic engaged volunteers (in fieldwork and providing DNA samples) and citizen science projects. During this time the National Geographic Society sold non-profit self-testing kits to members of the general public who wished to participate in the project as "citizen scientists". Such outreach for public participation in research has been encouraged by organizations such as International Society of Genetic Genealogy (ISOGG), which is seeking to promote benefits from scientific research. This includes supporting, organization and dissemination of personal DNA (genetic) testing.
The ISOGG supports citizen participation in genetic research, and believes such volunteers have provided valuable information and research to the professional scientific community.
In a 2013 speech to the Southern California Genealogical Society, Spencer Wells discussed its encouragement of citizen scientists. He said:
Since 2005, the Genographic Project has used the latest genetic technology to expand our knowledge of the human story, and its pioneering use of DNA testing to engage and involve the public in the research effort has helped to create a new breed of "citizen scientist." Geno 2.0 expands the scope for citizen science, harnessing the power of the crowd to discover new details of human population history.
== Criticism ==
Shortly after the announcement of the project in April 2005, the Indigenous Peoples Council on Biocolonialism (IPCB) noted its connections to controversial issues (such as concern among some tribes that the results of genetic human migration studies might indicate that Native Americans are not indigenous to North America). The IPCB recommended against indigenous people participating.
The founder of IPCB, Debra Harry, offered a rationale for why Indigenous people were discouraged to participate in the Genographic Project. According to Harry, a Northern Paiute Native American and Associate Professor in Indigenous Studies at Nevada University, the Genographic Project resulted in a human genetic testing practice that appeared to mask an ulterior motive rather than mere scientific research. Particularly, the great concern about the possible political interest behind the Genographic Project, motivated the IPCB to preemptively alert the global indigenous community on the “not so altruistic motivations” of the project. Additionally, IPCB argues that the Genographic project not only provides no direct benefit to Indigenous peoples but instead raises considerable risks. Such risks, raised by Harry in an interview released in December 2005, were used to advocate against the indigenous participation in the project. Another comment made by IPCB founder Debra Harry was that the Genographic Project served as a method to discredit kin relations through the possibility that ancestral identities may be invalidated and to deny Indigenous peoples’ access and authority over the resource-rich territories that they had for long inhabited. The IPCB also identified another attempt at biocolonialism in the Genographic Project. The latter involved the high probability of genetic testing results producing errors such as false negatives and positives that lead to the misidentification of Native people as non-Native and vice versa. Another negative consequence expressed by TallBear is the risk that an individual's cultural identity can be conclusively established through biocolonialist projects such as the Genographic Project. Ultimately, TallBear's argument is in close agreement with Harry's concerns regarding the Genographic Project and serves as a significant force motivating IPCB to advocate against Biocolonialism.
In May 2006, the project came to the attention of the United Nations Permanent Forum on Indigenous Issues (UNPFII). UNPFII conducted investigations into the objectives of the Genographic Project, and recommended that National Geographic and other sponsors suspend the project. Concerns were that the knowledge gleaned from the research could clash with long-held beliefs of indigenous peoples and threaten their cultures. There were also concerns that indigenous claims to land rights and other resources could be threatened.
As of December 2006, some federally recognized tribes in the United States declined to take part in the study including Maurice Foxx, chairman of the Massachusetts Commission on Indian Affairs and a member of the Mashpee Wampanoag.
Not all Indigenous peoples agree with his position; as of December 2012, more than 70,000 indigenous participants from the Americas, Africa, Asia, Europe, and Oceania had joined the project.
== See also ==
== References ==
== External links ==
Official sites
Genographic Project official site at National Geographic
Arizona Research Laboratories (ARL)
Waitt Family Foundation
News articles
"Finding the roots of modern humans". CNN. 14 April 2005.
"'Genographic Project' aims to tell us where we came from". USA Today. 17 April 2005.
"Indigenous Peoples Oppose National Geographic", Indigenous Peoples Council on Biocolonialism, 13 April 2005.
"Tracking the Truth", DB2 Magazine (IBM), information about IBM's role in the project. December 2006.
Genographic Success Stories
"Crusaders left genetic legacy". BBC News. 27 March 2008.
"Human Line 'Nearly split in Two'". BBC News. 24 April 2008.
Videos
Spencer Wells: Building a family tree for all humanity on YouTube, on TED, 29 August 2008. | Wikipedia/Genographic_Project |
Single-molecule real-time (SMRT) sequencing is a parallelized single molecule DNA sequencing method. Single-molecule real-time sequencing utilizes a zero-mode waveguide (ZMW). A single DNA polymerase enzyme is affixed at the bottom of a ZMW with a single molecule of DNA as a template. The ZMW is a structure that creates an illuminated observation volume that is small enough to observe only a single nucleotide of DNA being incorporated by DNA polymerase. Each of the four DNA bases is attached to one of four different fluorescent dyes. When a nucleotide is incorporated by the DNA polymerase, the fluorescent tag is cleaved off and diffuses out of the observation area of the ZMW where its fluorescence is no longer observable. A detector detects the fluorescent signal of the nucleotide incorporation, and the base call is made according to the corresponding fluorescence of the dye.
== Technology ==
The DNA sequencing is done on a chip that contains many ZMWs. Inside each ZMW, a single active DNA polymerase with a single molecule of single stranded DNA template is immobilized to the bottom through which light can penetrate and create a visualization chamber that allows monitoring of the activity of the DNA polymerase at a single molecule level. The signal from a phospho-linked nucleotide incorporated by the DNA polymerase is detected as the DNA synthesis proceeds which results in the DNA sequencing in real time.
=== Template preparation ===
To prepare the library, DNA fragments are put into a circular form using hairpin adapter ligations.
=== Phospholinked nucleotide ===
For each of the nucleotide bases, there is a corresponding fluorescent dye molecule that enables the detector to identify the base being incorporated by the DNA polymerase as it performs the DNA synthesis. The fluorescent dye molecule is attached to the phosphate chain of the nucleotide. When the nucleotide is incorporated by the DNA polymerase, the fluorescent dye is cleaved off with the phosphate chain as a part of a natural DNA synthesis process during which a phosphodiester bond is created to elongate the DNA chain. The cleaved fluorescent dye molecule then diffuses out of the detection volume so that the fluorescent signal is no longer detected.
=== Zero-Mode Waveguide ===
The zero-mode waveguide (ZMW) is a nanophotonic confinement structure that consists of a circular hole in an aluminum cladding film deposited on a clear silica substrate.
The ZMW holes are ~70 nm in diameter and ~100 nm in depth. Due to the behavior of light when it travels through a small aperture, the optical field decays exponentially inside the chamber.
The observation volume within an illuminated ZMW is ~20 zeptoliters (20 X 10−21 liters). The observation volume being so low eliminates background fluorescence from the free, unincorporated fluorescent nucleotides present in the solution. Within this volume, the activity of DNA polymerase incorporating a single nucleotide can be readily detected where each nucleotide is a separate color.
== Sequencing Performance ==
Sequencing performance can be measured in read length, accuracy, and total throughput per experiment. PacBio sequencing systems using ZMWs have the advantage of long read lengths, although error rates are on the order of 5-15% and sample throughput is lower than Illumina sequencing platforms.
On 19 Sep 2018, Pacific Biosciences [PacBio] released the Sequel 6.0 chemistry, synchronizing the chemistry version with the software version. Performance is contrasted for large-insert libraries with high molecular weight DNA versus shorter-insert libraries below ~15,000 bases in length. For larger templates average read lengths are up to 30,000 bases. For shorter-insert libraries, average read length are up to 100,000 bases while reading the same molecule in a circle several times. The latter shorter-insert libraries then yield up to 50 billion bases from a single SMRT Cell.
== History ==
Pacific Biosciences (PacBio) commercialized SMRT sequencing in 2011, after releasing a beta version of its RS instrument in late 2010.
=== RS and RS II ===
At commercialization, read length had a normal distribution with a mean of about 1100 bases. A new chemistry kit released in early 2012 increased the sequencer's read length; an early customer of the chemistry cited mean read lengths of 2500 to 2900 bases.
The XL chemistry kit released in late 2012 increased average read length to more than 4300 bases.
On August 21, 2013, PacBio released a new DNA polymerase Binding Kit P4. This P4 enzyme has average read lengths of more than 4,300 bases when paired with the C2 sequencing chemistry and more than 5,000 bases when paired with the XL chemistry. The enzyme’s accuracy is similar to C2, reaching QV50 between 30X and 40X coverage. The resulting P4 attributes provided higher-quality assemblies using fewer SMRT Cells and with improved variant calling. When coupled with input DNA size selection (using an electrophoresis instrument such as BluePippin) yields average read length over 7 kilobases.
On October 3, 2013, PacBio released new reagent combination for PacBio RS II, the P5 DNA polymerase with C3 chemistry (P5-C3). Together, they extend sequencing read lengths to an average of approximately 8,500 bases, with the longest reads exceeding 30,000 bases. Throughput per SMRT cell is around 500 million bases demonstrated by sequencing results from the CHM1 cell line.
On October 15, 2014, PacBio announced the release of new chemistry P6-C4 for the RS II system, which represents the company's 6th generation of polymerase and 4th generation chemistry--further extending the average read length to 10,000 - 15,000 bases, with the longest reads exceeding 40,000 bases. The throughput with the new chemistry was estimated between 500 million to 1 billion bases per SMRT Cell, depending on the sample being sequenced. This was the final version of chemistry released for the RS instrument.
Throughput per experiment for the technology is both influenced by the read length of DNA molecules sequenced as well as total multiplex of a SMRT Cell. The prototype of the SMRT Cell contained about 3000 ZMW holes that allowed parallelized DNA sequencing. At commercialization, the SMRT Cells were each patterned with 150,000 ZMW holes that were read in two sets of 75,000. In April 2013, the company released a new version of the sequencer called the "PacBio RS II" that uses all 150,000 ZMW holes concurrently, doubling the throughput per experiment. The highest throughput mode in November 2013 used P5 binding, C3 chemistry, BluePippin size selection, and a PacBio RS II officially yielded 350 million bases per SMRT Cell though a human de novo data set released with the chemistry averaging 500 million bases per SMRT Cell. Throughput varies based on the type of sample being sequenced. With the introduction of P6-C4 chemistry typical throughput per SMRT Cell increased to 500 million bases to 1 billion bases.
=== Sequel ===
In September 2015, the company announced the launch of a new sequencing instrument, the Sequel System, that increased capacity to 1 million ZMW holes.
With the Sequel instrument initial read lengths were comparable to the RS, then later chemistry releases increased read length.
On January 23, 2017, the V2 chemistry was released. It increased average read lengths to between 10,000 and 18,000 bases.
On March 8, 2018, the 2.1 chemistry was released. It increased average read length to 20,000 bases and half of all reads above 30,000 bases in length. Yield per SMRT Cell increased to 10 or 20 billion bases, for either large-insert libraries or shorter-insert (e.g. amplicon) libraries respectively.
On 19 September 2018, the company announced the Sequel 6.0 chemistry with average read lengths increased to 100,000 bases for shorter-insert libraries and 30,000 for longer-insert libraries. SMRT Cell yield increased up to 50 billion bases for shorter-insert libraries.
=== 8M Chip ===
In April 2019 the company released a new SMRT Cell with eight million ZMWs, increasing the expected throughput per SMRT Cell by a factor of eight. Early access customers in March 2019 reported throughput over 58 customer run cells of 250 GB of raw yield per cell with templates about 15 kb in length, and 67.4 GB yield per cell with templates in higher weight molecules. System performance is now reported in either high-molecular-weight continuous long reads or in pre-corrected HiFi (also known as Circular Consensus Sequence (CCS)) reads. For high-molecular-weight reads roughly half of all reads are longer than 50 kb in length.
The HiFi performance includes corrected bases with quality above Phred score Q20, using repeated amplicon passes for correction. These take amplicons up to 20kb in length.
== Application ==
Single-molecule real-time sequencing may be applicable for a broad range of genomics research.
For de novo genome sequencing, read lengths from the single-molecule real-time sequencing are comparable to or greater than that from the Sanger sequencing method based on dideoxynucleotide chain termination. The longer read length allows de novo genome sequencing and easier genome assemblies. Scientists are also using single-molecule real-time sequencing in hybrid assemblies for de novo genomes to combine short-read sequence data with long-read sequence data. In 2012, several peer-reviewed publications were released demonstrating the automated finishing of bacterial genomes, including one paper that updated the Celera Assembler with a pipeline for genome finishing using long SMRT sequencing reads. In 2013, scientists estimated that long-read sequencing could be used to fully assemble and finish the majority of bacterial and archaeal genomes.
The same DNA molecule can be resequenced independently by creating the circular DNA template and utilizing a strand displacing enzyme that separates the newly synthesized DNA strand from the template. In August 2012, scientists from the Broad Institute published an evaluation of SMRT sequencing for SNP calling.
The dynamics of polymerase can indicate whether a base is methylated. Scientists demonstrated the use of single-molecule real-time sequencing for detecting methylation and other base modifications. In 2012 a team of scientists used SMRT sequencing to generate the full methylomes of six bacteria. In November 2012, scientists published a report on genome-wide methylation of an outbreak strain of E. coli.
Long reads make it possible to sequence full gene isoforms, including the 5' and 3' ends. This type of sequencing is useful to capture isoforms and splice variants.
SMRT sequencing has several applications in reproductive medical genetics research when investigating families with suspected parental gonadal mosaicism. Long reads enable haplotype phasing in patients to investigate parent-of-origin of mutations. Deep sequencing enables determination of allele frequencies in sperm cells, of relevance for estimation of recurrence risk for future affected offspring.
== References ==
== External links ==
Report from the BioIT World.com
Report from New York Times | Wikipedia/Single-molecule_real-time_sequencing |
Applied Biosystems is one of various brands under the Life Technologies brand of Thermo Fisher Scientific corporation. The brand is focused on integrated systems for genetic analysis, which include computerized machines and the consumables used within them (such as reagents).
In 2008, a merger between Applied Biosystems and Invitrogen was finalized, creating Life Technologies. The latter was acquired by Thermo Fisher Scientific in 2014. Prior to 2008, the Applied Biosystems brand was owned by various entities in a corporate group parented by PerkinElmer. The roots of Applied Biosystems trace back to GeneCo (Genetic Systems Company), a pioneer biotechnology company founded in 1981 in Foster City, California. Through the 1980s and early 1990s, Applied Biosystems, Inc. operated independently and manufactured biochemicals and automated genetic engineering and diagnostic research instruments, including the principal brand of DNA sequencing machine used by the Human Genome Project consortium centers. Applied Biosystems' close ties to the consortium project led to the idea for the founding of Celera Genomics in 1998 as one of several independent competitors to the consortium.
In 1993 Applied Biosystems, Inc., was delisted from the NASDAQ when it was acquired by the old company known then as Perkin-Elmer. As the PE Applied Biosystems Division under that parent in 1998, it became consolidated with other acquisitions as the primary PE Biosystems Division. In 1999 its parent company reorganized and changed its name to PE Corporation, and the PE Biosystems Group (formerly again became publicly traded, as a tracking stock of its parent, along with its sister tracking stock company, Celera Genomics. In 2000 the parent became Applera Corporation. The Applied Biosystems name also returned that year, in the name change of the tracking stock from PE Biosystems Group to Applera Corporation-Applied Biosystems Group, an S&P 500 company, which remains as a publicly traded operating group within Applera Corp., along with its sibling operating group, Applera Corporation-Celera Group. Applera derives its name from the combination of its two component groups' names, Appl(iedCel)era In November 2008, a merger between Applied Biosystems and Invitrogen was finalized "creating a global leader in biotechnology reagents and systems". The new company was called Life Technologies.
== History ==
In 1981, the company was founded by two scientist/engineers from Hewlett Packard, Sam Eletr and André Marion based on technology developed by Leroy Hood and Marvin H. Caruthers.
In 1982, Applied Biosystems released its first commercial instrument, the Model 470A Protein Sequencer. The machine enabled scientists to determine the order of amino acids within a purified protein, which in turn correlated with the protein's function. With 40 employees, the company, reported first-time revenue of US$402,000.
In 1983, the company was led by its president and Chairman of the Board, Sam Eletr and Chief Operating Officer Andre Marion, the company doubled its number of employees to 80, and its stock went public on the NASDAQ exchange under the symbol ABIO, with revenues of US$5.9 million. A new product was a fluorescent molecular tag for immunodiagnostic assays.
The company released its second commercial instrument, the Model 380A DNA Synthesizer, which made oligonucleotides, short DNA strands, for polymerase chain reaction (PCR), DNA sequencing, and gene identification. The two sequencer and synthesizer products allowed molecular biologists to clone genes by building oligonucleotides with the desired protein's DNA sequence.
Automated DNA sequencing began at the California Institute of Technology, using fluorescent dyes, with Rights to the technology granted to Applied Biosystems. At CIT, Dr. Leroy Hood and Dr. Lloyd Smith, together pioneered those first DNA sequencing machines.
In 1984, Applied Biosystems sales revenue tripled to over US$18 million, with a second yearly profit, and with over 200 employees.
Services included synthesizing custom DNA and protein fragments, and the sequencing of protein samples submitted from customers. The third major instrument made by Applied, the Model 430A Peptide Synthesizer, was introduced.
In 1985, Applied Biosystems sales revenue grew nearly 70% to over US$35 million, with a third yearly profit. Two new products included the Model 380B DNA Synthesizer and the 381A DNA Synthesizer. That year the company went international for the first time, when it established a wholly owned subsidiary in Great Britain to save shipping costs on chemical sales, which overall by then accounted for 17% of sales.
Also in 1985, Applied Biosystems acquired Brownlee Labs, a manufacturer of columns and pumps for high-performance liquid chromatography (HPLC) systems, after its founder, Robert Brownlee was diagnosed with AIDS-related complex in 1984. Brownlee's technology brought the new on-line 120A PTH Amino Acid Analyzer.
However, Brownlee then began a new company, which was viewed by Applied as a competitor. In 1989 Applied and Brownlee settled in a lawsuit over the conflict. As late as 1990, Brownlee publicly discussed what had been his contributions in the rocky relationship with Applied, before he died early the next year.
In 1986, Andre Marion became president and Chief Executive Officer. Sales revenue increased by 45% to nearly US$52 million. The company introduced six new products, totalling eleven automated instruments. The release of the Model 370A DNA Sequencing System, using fluorescent tags, revolutionized gene discovery. The Model 340A Nucleic Acid Extractor became used in medical labs to isolate DNA from bacteria, blood, and tissue.
In 1987, Sam Eletr resigned for health reasons. Revenues increase by 63% to nearly US$85 million, with 788 employees, and another six new instruments. Applied Biosystems acquired the Kratos Division of Spectros International PLC.
By 1988, the product line had increased to over 25 different automated instruments, over 400 liquid chromatography columns and components, and about 320 chemicals, biochemicals, and consumables. Sales revenue grew to over US$132 million, with almost 1000 employees in eight countries. In that year for the first time, genetic science reached the milestone of being able to identify individuals by their DNA.
In 1989, sales revenue reached nearly $160 million. Applied Biosystems maintained 15 offices in 9 different countries, and introduced four new products. The company developed enzyme-based reagent kits made by Promega Corporation, and in the new field of bioinformatics, licensed with TRW Inc. Also, joint marketing began with Perkin-Elmer Corporation and Cetus Corporation (formerly of instruments and reagents for DNA replication, the fastest growing segment in biotechnology.
In 1990, instrument sales underwent a cyclical slowdown, as the economy entered the 1990–91 recession. For the first year, Applied revenues did not grow, and came in at less than $159 million, with 1,334 employees. New company developments included new instrumentation for robotics and detection of DNA fragments using the company's fluorescent labelling.
Also in 1990, the U.S. government approved financing to support the Human Genome Project. Dr. James D. Watson, who founded the consortium, forecast that the project could be completed in 15 years from its 1990 starting date, at a cost of cost US$3 billion. Over the next couple years, Japan began a project to sequence the rice genome, and other laboratories initiated programs to sequence the mouse, fruit fly, and yeast genomes.
In 1991, Applied sales revenue grew slightly, to almost $164 million, with consumables and service contracts up by 24% to account for 47% of total sales, and DNA sequencer and DNA synthesis instruments having record sales. Forty-five new consumable products and six new instruments were introduced.
In 1992, sales revenue grew by more than 11% to over $182 million, with Europe representing 25% of revenue, and Asia and the Pacific Rim accounting for 26%. The company formed a new subsidiary, Lynx Therapeutics, Inc., to focus on antisense DNA research in the area of therapeutics for chronic myelogenous leukemia, melanoma, colorectal cancer, and AIDS.
=== Perkin-Elmer ===
In February 1993 Applied Biosystems was acquired by Perkin-Elmer, and became the Applied Biosystems Division, as part of the Life Sciences markets segment of that company. Andre Marion, who had been Applied Biosystems's Chairman, President and CEO, became a Senior Vice President of Perkin-Elmer, and President of the Applied Biosystems Division. That year the company was the world's leading manufacturer of instruments and reagents for polymerase chain reaction (PCR). It marketed PCR reagents kits in alliance with Hoffman-La Roche Inc.
In 1994, Perkin-Elmer reported net revenues of over $1 billion, of which Life Sciences accounted for 42% of the business. The company has 5,954 employees. A brand-new highly competitive genomics industry had formed for the development of new pharmaceuticals, based on the work of the Human Genome Project. Companies such as Sequana Therapeutics in San Diego, Human Genome Sciences in Maryland, Myriad Genetics in Utah, INCYTE Pharmaceuticals (later Incyte Genomics) in California, and Millennium Pharmaceuticals relied on the Applied Biosystems Division, which made thermal cyclers and automated sequencers for these new genomics companies.
In 1995, upon Andre Marion retirement, Mike Hunkapiller became President of PE Applied Biosystems Division which sold its 30,000th thermal cycler. To meet Human Genome Project goals, Perkin-Elmer developed mapping kits with markers every 10 million bases along each chromosome. Also that year, DNA fingerprinting using PCR became accepted in court as reliable forensic evidence.
In 1996, Perkin-Elmer acquired Tropix, Inc., a chemiluminescence company, for its life sciences division.
=== PE Applied Biosystems ===
In September 1995, Tony L. White from Baxter International Inc. became president and Chief Executive Officer of Perkin-Elmer. In 1996 the company was reorganized into two separate operating divisions, Analytical Instruments and PE Applied Biosystems. The PE Applied Biosystems division accounted for half of Perkin-Elmer's total revenue, with net revenues up by 26%.
In 1997, revenues reached almost US$1.3 billion, of which PE Applied Biosystems was US$653 million. The company acquired GenScope, Inc., and Linkage Genetics, Inc. The Linkage Genetics unit was combined with Zoogen to form PE AgGen, focused on genetic analysis services for plant and animal breeding. The PE Applied Biosystems division partnered with Hyseq, Inc., for work on the new DNA chip technology, and also worked with Tecan U.S., Inc., on combinatorial chemistry automation systems, and also with Molecular Informatics, Inc. on genetic data management and analysis automated systems.
=== PE Biosystems ===
In 1998, PE Applied Biosystems became PE Biosystems, and the division's revenues reached US$921.8 million. In January 1998 Perkin-Elmer acquired PerSeptive Biosystems (formerly of Framingham, Massachusetts. It was a leader in the bio-instrumentation field where it made biomolecule purification systems for protein analysis. Noubar Afeyan, Ph.D., had been the founder, Chairman, and CEO of PerSeptive, and with the Perkin-Elmer successor company he set up the later tracking stock for Celera.
In 1998, Perkin-Elmer formed the PE Biosystems division, by consolidating Applied Biosystems, PerSeptive Biosystems, Tropix and PE Informatics. Informatics was formed from the Perkin-Elmer combination of two other acquisitions, Molecular Informatics and Nelson Analytical Systems, with existing units of Perkin-Elmer.
While planning the next new generation of machines, PE Biosystems' president, Michael W. Hunkapiller, calculated that it would be possible for their own private industry to decode the human genome before the academic consortium could complete it, by using the resources of a single, industrial-scale center, even though it would require starting from scratch. It was a bold prediction, given that the consortium target date set by Dr. Watson back in 1990 had been the forward year of 2005, only seven years away, and with the consortium already half the way to the completion target date.
Also, it meant that Dr. Hunkapiller's idea would require competing against his own customers, to all of whom Applied Biosystems sold its sequencing machines and their chemical reagents. However, he calculated that it would also mean doubling the market for that equipment.
Hunkapiller brought in Dr. J. Craig Venter to direct the project. Tony White, president of the Perkin-Elmer Corporation backed Hunkapiller on the venture. They organized the new company to accomplish the task. In May 1998, Celera Genomics was formed, to rapidly accelerate the human DNA sequencing process. Dr. Venter boldly declared to the media that he would complete the genome decoding by 2001. That bold announcement prompted the academic consortium to accelerate their own deadline by a couple years, to 2003.
Also in 1998, PE Biosystems partnered with Hitachi, Ltd. to develop electrophoresis-based genetic analysis systems, which resulted in their chief new genomics instrument, the ABI PRISM 3700 DNA Analyzer, which advanced the Human Genome sequencing project by nearly five years ahead of schedule. The partnerships sold hundreds of the 3700 analyzers to Celera, and also to others worldwide.
The new machine cost US$300,000 each, but was a major leap beyond its predecessor, the 377, and was fully automated, allowing genetic decoding to run around the clock with little supervision. According to Venter, the machine was so revolutionary that it could decode in a single day the same amount of genetic material that most DNA labs could produce in a year.
The public consortium also bought one of the PE Biosystems 3700 sequencers, and had plans to buy 200 more. The machine proved to be so fast that by late March 1999 the consortium announced that it had revised its timeline, and would release by the Spring of 2000 a "first draft sequence" for 80% of the human genome.
At year end 1998, the PE Biosystems Group's sales reached US$940 million.
=== PE Corporation ===
In 1999, to focus on the new genomics, Perkin-Elmer Corporation was renamed PE Corporation, and sold its old Analytical Instruments division to EG&G, Inc., which also acquired the Perkin-Elmer name. PE Biosystems remained with PE Corp., and became PE Biosystems Group, with 3,500 employees and net revenues of over $1.2 billion. New instruments were developed and sold for forensic human identification, protein identification and characterization, metabolite pathway identification, and lead compound identification from combinatorial libraries.
On April 27, 1999, the shareholders of Perkin-Elmer Corporation approved the reorganization of Perkin-Elmer into PE Corporation, a pure-play life science company. Each share of the Perkin-Elmer stock (PKN) was to be exchanged for one share and for +1⁄2 of a share respectively of the two new common share tracking stocks for the two component Life Sciences groups, PE Biosystems Group and Celera Genomics Group.
On April 28, 1999, the two replacement tracking stocks for the new PE Corporation were issued to shareholders. Dr. Michael W. Hunkapiller remained as a Senior Vice President of PE Corporation, and as president of PE Biosystems.
On May 6, 1999, the recapitalization of the company resulted in issuance of the two new classes of common stock, called PE Corporation-PE Biosystems Group Common Stock and PE Corporation-Celera Genomics Group Common Stock. On that date, trading began in both new stocks on the New York Stock Exchange, to great excitement.
On June 17, 1999, the Board of PE Corporation announced a two-for-one split of PE Biosystems Group Common Stock.
By June 2000, the genomics segment of the technology bubble was peaking. Celera Genomics (CRA) and PE Biosystems (PEB) were among five genetics pioneers leading at that time, along with Incyte Genomics, Human Genome Sciences, and Millennium Pharmaceuticals. All five of those stocks by then had exceeded a price above $100 per share in the market, before ultimately crashing back down.
=== Applera ===
On November 30, 2000, PE Corporation changed its name to Applera, combining the two partial names Applied and Celera into one, with 5,000 employees. PE Biosystems Group was renamed once again to Applied Biosystems Group, and changed its ticker symbol from PEB to ABI. Its net revenues rose to almost US$1.4 billion. Celera that year made milestone headlines when it announced that it had completed the sequencing and first assembly of the two largest genomes in history, that of the fruit fly, and of the human.
In 2001, the Applied Biosystems division of Applera reached revenues of US$1.6 billion, and developed a new workstation instrument specifically for the new field of proteomics, which had become Celera's new core business focus, as it shifted away from gene discovery. The instrument analyzed 1,000 protein samples per hour.
On April 22, 2002, the Celera Genomics Group announced its decision to shift the role of marketing data from its genetic database over to its sister company, the Applied Biosystems Group. Celera would instead develop pharmaceutical drugs. Applied Biosystems was a better fit for the database, because Applied already had the huge sales force in place for the marketing of its instruments. Plans were to expand those sales and those of the database into an electronic commerce system.
In 2002, Applied Biosystems reached revenues of US$1.6 billion for the year, and took control from Celera of the support of Celera Discovery System (CDS), a data tool to answer specific genomic and proteomic queries, involving the new genetic data field of tens of thousands of single-nucleotide polymorphisms (SNPs) within the human genome. The company developed another new tool, which combined the first ever union of triple quadrupole and ion trap technologies, in proteomics research.
The database itself would remain with Celera, because of shareholder approval complications. Celera would retain responsibility for its maintenance and support to existing customers, and would receive royalties from Applied Biosystems.
In 2003, Catherine Burzik joined Applied's management, from Ortho-Clinical Diagnostics. Applied developed a new tool which measured antibody/antigen binding in real-time kinetic analysis of up to 400 binding interactions simultaneously.
In 2004, Mike Hunkapiller retired and Cathy Burzik replaced him as President of Applied Biosystems. Applera collaborated with General Electric, Abbott Laboratories, Seattle Genetics, and Merck in diagnostics development. Applied Biosystmes also teamed with Northrop Grumman and Cepheid of Sunnyvale, California, to detect Bacillus anthracis during the anthrax contamination case of the U.S. Postal Service.
In 2005, the company released new tools for small molecule quantitation in pharmaceutical drug development. In Mexico, Applied Biosystems collaborated with the National Institute of Genomic Medicine of Mexico (Instituto Nacional de Medicina Genomica or INMEGEN), and established an Applied Biosystems Sequencing and Genotyping Unit at INMEGEN.
In 2006, Applied Biosystems acquired the Research Products Division of Ambion, a supplier of RNA-based reagents and products. That year, with the Influenza A Subtype H5N1 "avian flu" strain scare, the company launched a global initiative to identify and track such infectious diseases.
In 2006, Applied Biosystems also acquired Agencourt Personal Genomics, located in Beverly, MA, to commercialize Agencourt's SOLiD sequencing system.
In 2007, ABI Solid Sequencing, a next-gen DNA sequencing platform, was announced. Mark Stevenson was appointed president and Chief Operating Officer of Applied Biosystems.
In November 2008, Applied Biosystems merged with Invitrogen, forming Life Technologies, which was acquired by Thermo Fisher Scientific in 2014.
== See also ==
2 Base Encoding
ABI Solid Sequencing
Next-generation sequencing
Illumina (company)
454 Life Sciences
== References ==
== External links ==
Applied Biosystems Historical SEC Filings | Wikipedia/Applied_Biosystems |
A DNA sequencer is a scientific instrument used to automate the DNA sequencing process. Given a sample of DNA, a DNA sequencer is used to determine the order of the four bases: G (guanine), C (cytosine), A (adenine) and T (thymine). This is then reported as a text string, called a read. Some DNA sequencers can be also considered optical instruments as they analyze light signals originating from fluorochromes attached to nucleotides.
The first automated DNA sequencer, invented by Lloyd M. Smith, was introduced by Applied Biosystems in 1987. It used the Sanger sequencing method, a technology which formed the basis of the "first generation" of DNA sequencers and enabled the completion of the human genome project in 2001. This first generation of DNA sequencers are essentially automated electrophoresis systems that detect the migration of labelled DNA fragments. Therefore, these sequencers can also be used in the genotyping of genetic markers where only the length of a DNA fragment(s) needs to be determined (e.g. microsatellites, AFLPs).
The Human Genome Project spurred the development of cheaper, high throughput and more accurate platforms known as Next Generation Sequencers (NGS) to sequence the human genome. These include the 454, SOLiD and Illumina DNA sequencing platforms. Next generation sequencing machines have increased the rate of DNA sequencing substantially, as compared with the previous Sanger methods. DNA samples can be prepared automatically in as little as 90 mins, while a human genome can be sequenced at 15 times coverage in a matter of days.
More recent, third-generation DNA sequencers such as PacBio SMRT and Oxford Nanopore offer the possibility of sequencing long molecules, compared to short-read technologies such as Illumina SBS or MGI Tech's DNBSEQ.
Because of limitations in DNA sequencer technology, the reads of many of these technologies are short, compared to the length of a genome therefore the reads must be assembled into longer contigs. The data may also contain errors, caused by limitations in the DNA sequencing technique or by errors during PCR amplification. DNA sequencer manufacturers use a number of different methods to detect which DNA bases are present. The specific protocols applied in different sequencing platforms have an impact in the final data that is generated. Therefore, comparing data quality and cost across different technologies can be a daunting task. Each manufacturer provides their own ways to inform sequencing errors and scores. However, errors and scores between different platforms cannot always be compared directly. Since these systems rely on different DNA sequencing approaches, choosing the best DNA sequencer and method will typically depend on the experiment objectives and available budget.
== History ==
The first DNA sequencing methods were developed by Gilbert (1973) and Sanger (1975). Gilbert introduced a sequencing method based on chemical modification of DNA followed by cleavage at specific bases whereas Sanger's technique is based on dideoxynucleotide chain termination. The Sanger method became popular due to its increased efficiency and low radioactivity. The first automated DNA sequencer was the AB370A, introduced in 1986 by Applied Biosystems. The AB370A was able to sequence 96 samples simultaneously, 500 kilobases per day, and reaching read lengths up to 600 bases. This was the beginning of the "first generation" of DNA sequencers, which implemented Sanger sequencing, fluorescent dideoxy nucleotides and polyacrylamide gel sandwiched between glass plates - slab gels. The next major advance was the release in 1995 of the AB310 which utilized a linear polymer in a capillary in place of the slab gel for DNA strand separation by electrophoresis. These techniques formed the base for the completion of the human genome project in 2001. The human genome project spurred the development of cheaper, high throughput and more accurate platforms known as Next Generation Sequencers (NGS). In 2005, 454 Life Sciences released the 454 sequencer, followed by Solexa Genome Analyzer and SOLiD (Supported Oligo Ligation Detection) by Agencourt in 2006. Applied Biosystems acquired Agencourt in 2006, and in 2007, Roche bought 454 Life Sciences, while Illumina purchased Solexa. Ion Torrent entered the market in 2010 and was acquired by Life Technologies (now Thermo Fisher Scientific). And BGI started manufacturing sequencers in China after acquiring Complete Genomics under their MGI arm. These are still the most common NGS systems due to their competitive cost, accuracy, and performance.
More recently, a third generation of DNA sequencers was introduced. The sequencing methods applied by these sequencers do not require DNA amplification (polymerase chain reaction – PCR), which speeds up the sample preparation before sequencing and reduces errors. In addition, sequencing data is collected from the reactions caused by the addition of nucleotides in the complementary strand in real time. Two companies introduced different approaches in their third-generation sequencers. Pacific Biosciences sequencers utilize a method called Single-molecule real-time (SMRT), where sequencing data is produced by light (captured by a camera) emitted when a nucleotide is added to the complementary strand by enzymes containing fluorescent dyes. Oxford Nanopore Technologies is another company developing third-generation sequencers using electronic systems based on nanopore sensing technologies.
== Manufacturers of DNA sequencers ==
DNA sequencers have been developed, manufactured, and sold by the following companies, among others.
=== Roche ===
The 454 DNA sequencer was the first next-generation sequencer to become commercially successful. It was developed by 454 Life Sciences and purchased by Roche in 2007. 454 utilizes the detection of pyrophosphate released by the DNA polymerase reaction when adding a nucleotide to the template strain.
Roche currently manufactures two systems based on their pyrosequencing technology: the GS FLX+ and the GS Junior System. The GS FLX+ System promises read lengths of approximately 1000 base pairs while the GS Junior System promises 400 base pair reads. A predecessor to GS FLX+, the 454 GS FLX Titanium system was released in 2008, achieving an output of 0.7G of data per run, with 99.9% accuracy after quality filter, and a read length of up to 700bp. In 2009, Roche launched the GS Junior, a bench top version of the 454 sequencer with read length up to 400bp, and simplified library preparation and data processing.
One of the advantages of 454 systems is their running speed. Manpower can be reduced with automation of library preparation and semi-automation of emulsion PCR. A disadvantage of the 454 system is that it is prone to errors when estimating the number of bases in a long string of identical nucleotides. This is referred to as a homopolymer error and occurs when there are 6 or more identical bases in row. Another disadvantage is that the price of reagents is relatively more expensive compared with other next-generation sequencers.
In 2013 Roche announced that they would be shutting down development of 454 technology and phasing out 454 machines completely in 2016 when its technology became noncompetitive.
Roche produces a number of software tools which are optimised for the analysis of 454 sequencing data. Such as,
GS Run Processor converts raw images generated by a sequencing run into intensity values. The process consists of two main steps: image processing and signal processing. The software also applies normalization, signal correction, base-calling and quality scores for individual reads. The software outputs data in Standard Flowgram Format (or SFF) files to be used in data analysis applications (GS De Novo Assembler, GS Reference Mapper or GS Amplicon Variant Analyzer).
GS De Novo Assembler is a tool for de novo assembly of whole-genomes up to 3GB in size from shotgun reads alone or combined with paired end data generated by 454 sequencers. It also supports de novo assembly of transcripts (including analysis), and also isoform variant detection.
GS Reference Mapper maps short reads to a reference genome, generating a consensus sequence. The software is able to generate output files for assessment, indicating insertions, deletions and SNPs. Can handle large and complex genomes of any size.
Finally, the GS Amplicon Variant Analyzer aligns reads from amplicon samples against a reference, identifying variants (linked or not) and their frequencies. It can also be used to detect unknown and low-frequency variants. It includes graphical tools for analysis of alignments.
=== Illumina ===
Illumina produces a number of next-generation sequencing machines using technology acquired from Manteia Predictive Medicine and developed by Solexa. Illumina makes a number of next generation sequencing machines using this technology including the HiSeq, Genome Analyzer IIx, MiSeq and the HiScanSQ, which can also process microarrays.
The technology leading to these DNA sequencers was first released by Solexa in 2006 as the Genome Analyzer. Illumina purchased Solexa in 2007. The Genome Analyzer uses a sequencing by synthesis method. The first model produced 1G per run. During the year 2009 the output was increased from 20G per run in August to 50G per run in December. In 2010 Illumina released the HiSeq 2000 with an output of 200 and then 600G per run which would take 8 days. At its release the HiSeq 2000 provided one of the cheapest sequencing platforms at $0.02 per million bases as costed by the Beijing Genomics Institute.
In 2011 Illumina released a benchtop sequencer called the MiSeq. At its release the MiSeq could generate 1.5G per run with paired end 150bp reads. A sequencing run can be performed in 10 hours when using automated DNA sample preparation.
The Illumina HiSeq uses two software tools to calculate the number and position of DNA clusters to assess the sequencing quality: the HiSeq control system and the real-time analyzer. These methods help to assess if nearby clusters are interfering with each other.
=== Life Technologies ===
Life Technologies (now Thermo Fisher Scientific) produces DNA sequencers under the Applied Biosystems and Ion Torrent brands. Applied Biosystems makes the SOLiD next-generation sequencing platform, and Sanger-based DNA sequencers such as the 3500 Genetic Analyzer. Under the Ion Torrent brand, Applied Biosystems produces four next-generation sequencers: the Ion PGM System, Ion Proton System, Ion S5 and Ion S5xl systems. The company is also believed to be developing their new capillary DNA sequencer called SeqStudio that will be released early 2018.
SOLiD systems was acquired by Applied Biosystems in 2006. SOLiD applies sequencing by ligation and dual base encoding. The first SOLiD system was launched in 2007, generating reading lengths of 35bp and 3G data per run. After five upgrades, the 5500xl sequencing system was released in 2010, considerably increasing read length to 85bp, improving accuracy up to 99.99% and producing 30G per 7-day run.
The limited read length of the SOLiD has remained a significant shortcoming and has to some extent limited its use to experiments where read length is less vital such as resequencing and transcriptome analysis and more recently ChIP-Seq and methylation experiments. The DNA sample preparation time for SOLiD systems has become much quicker with the automation of sequencing library preparations such as the Tecan system.
The colour space data produced by the SOLiD platform can be decoded into DNA bases for further analysis, however software that considers the original colour space information can give more accurate results. Life Technologies has released BioScope, a data analysis package for resequencing, ChiP-Seq and transcriptome analysis. It uses the MaxMapper algorithm to map the colour space reads.
=== Beckman Coulter ===
Beckman Coulter (now Danaher) has previously manufactured chain termination and capillary electrophoresis-based DNA sequencers under the model name CEQ, including the CEQ 8000. The company now produces the GeXP Genetic Analysis System, which uses dye terminator sequencing. This method uses a thermocycler in much the same way as PCR to denature, anneal, and extend DNA fragments, amplifying the sequenced fragments.
=== Pacific Biosciences ===
Pacific Biosciences produces the PacBio RS and Sequel sequencing systems using a single molecule real time sequencing, or SMRT, method. This system can produce read lengths of multiple thousands of base pairs. Higher raw read errors are corrected using either circular consensus - where the same strand is read over and over again - or using optimized assembly strategies. Scientists have reported 99.9999% accuracy with these strategies. The Sequel system was launched in 2015 with an increased capacity and a lower price.
=== Oxford Nanopore ===
Oxford Nanopore Technologies' MinION sequencer is based on evolving nanopore sequencing technology to nucleic acid analyses. The device is four inches long and gets power from a USB port. MinION decodes DNA directly as the molecule is drawn at the rate of 450 bases/second through a nanopore suspended in a membrane. Changes in electric current indicate which base is present. Initially, the device was 60 to 85 percent accurate, compared with 99.9 percent in conventional machines. Even inaccurate results may prove useful because it produces long read lengths. In early 2021, researchers from University of British Columbia has used special molecular tags and able to reduce the five-to-15 per cent error rate of the device to less than 0.005 per cent even when sequencing many long stretches of DNA at a time. There are two more product iterations based on MinION; the first one is the GridION which is a slightly larger sequencer that processes up to five MinION flow cells at once. And, the second one is the PromethION which uses as many as 100,000 pores in parallel, more suitable for high volume sequencing.
=== MGI ===
MGI produces high-throughput sequencers for scientific research and clinical applications such as DNBSEQ-G50, DNBSEQ-G400, and DNBSEQ-T7, under a proprietary DNBSEQ technology. It is based upon DNA nanoball sequencing and combinatorial probe anchor synthesis technologies, in which DNA nanoballs (DNBs) are loaded onto a patterned array chip via the fluidic system, and later a sequencing primer is added to the adaptor region of DNBs for hybridization. DNBSEQ-T7 can generate short reads at a very large scale—up to 60 human genomes per day. DNBSEQ-T7 was used to generate 150 bp paired-end reads, sequencing 30X, to sequence the genome of SARS-CoV-2 or COVID-19 to identify the genetic variants predisposition in severe COVID-19 illness. Using a novel technique the researchers from China National GeneBank sequenced PCR-free libraries on MGI's PCR-free DNBSEQ arrays to obtain for the first time a true PCR-free whole genome sequencing. MGISEQ-2000 was used in single-cell RNA sequencing to study the underlying pathogenesis and recovery in COVID-19 patients, as published in Nature Medicine.
== Comparison ==
Current offerings in DNA sequencing technology show a dominant player: Illumina (December 2019), followed by PacBio, MGI and Oxford Nanopore.
== References == | Wikipedia/DNA_sequencer |
454 Life Sciences was a biotechnology company based in Branford, Connecticut that specialized in high-throughput DNA sequencing. It was acquired by Roche in 2007 and shut down by Roche in 2013 when its technology became noncompetitive, although production continued until mid-2016.
== History ==
454 Life Sciences was founded by Jonathan Rothberg and was originally known as 454 Corporation, a subsidiary of CuraGen. For their method for low-cost gene sequencing, 454 Life Sciences was awarded the Wall Street Journal's Gold Medal for Innovation in the Biotech-Medical category in 2005. The name 454 was the code name by which the project was referred to at CuraGen, and the numbers have no known special meaning.
In November 2006, Rothberg, Michael Egholm, and colleagues at 454 published a cover article with Svante Pääbo in Nature describing the first million base pairs of the Neanderthal genome, and initiated the Neanderthal Genome Project to complete the sequence of the Neanderthal genome by 2009.
In late March 2007, Roche Diagnostics acquired 454 Life Sciences for US$154.9 million. It remained a separate business unit.
In October 2013, Roche announced that it would shut down 454, and stop supporting the platform by mid-2016.
In May 2007, 454 published the results of Project "Jim": the sequencing of the genome of James Watson, co-discoverer of the structure of DNA.
== Technology ==
454 Sequencing used a large-scale parallel pyrosequencing system capable of sequencing roughly 400-600 megabases of DNA per 10-hour run on the Genome Sequencer FLX with GS FLX Titanium series reagents.
The system relied on fixing nebulized and adapter-ligated DNA fragments to small DNA-capture beads in a water-in-oil emulsion. The DNA fixed to these beads was then amplified by PCR. Each DNA-bound bead was placed into a ~29 μm well on a PicoTiterPlate, a fiber optic chip. A mix of enzymes such as DNA polymerase, ATP sulfurylase, and luciferase was also packed into the well. The PicoTiterPlate was then placed into the GS FLX System for sequencing.
454 released the GS20 sequencing machine in 2005, the first next-generation DNA sequencer on the market. In 2008, 454 Sequencing launched the GS FLX Titanium series reagents for use on the Genome Sequencer FLX instrument, with the ability to sequence 400-600 million base pairs per run with 400-500 base pair read lengths. In late 2009, 454 Life Sciences introduced the GS Junior System, a bench top version of the Genome Sequencer FLX System.
=== DNA library preparation and emPCR ===
Genomic DNA was fractionated into smaller fragments (300-800 base pairs) and polished (made blunt at each end). Short adaptors were then ligated onto the ends of the fragments. These adaptors provided priming sequences for both amplification and sequencing of the sample-library fragments. One adaptor (Adaptor B) contained a 5'-biotin tag for immobilization of the DNA library onto streptavidin-coated beads. After nick repair, the non-biotinylated strand was released and used as a single-stranded template DNA (sstDNA) library. The sstDNA library was assessed for its quality, and the optimal amount (DNA copies per bead) needed for emPCR is determined by titration.
The sstDNA library was immobilized onto beads. The beads containing a library fragment carried a single sstDNA molecule. The bead-bound library was emulsified with the amplification reagents in a water-in-oil mixture. Each bead was captured within its own microreactor where PCR amplification occurs. This resulted in bead-immobilized, clonally amplified DNA fragments.
=== Sequencing ===
Single-stranded template DNA library beads were added to the DNA Bead Incubation Mix (containing DNA polymerase) and were layered with Enzyme Beads (containing sulfurylase and luciferase) onto a PicoTiterPlate device. The device was centrifuged to deposit the beads into the wells. The layer of Enzyme Beads ensured that the DNA beads remained positioned in the wells during the sequencing reaction. The bead-deposition process was designed to maximize the number of wells that contain a single amplified library bead.
The loaded PicoTiterPlate device were placed into the Genome Sequencer FLX Instrument. The fluidics sub-system delivered sequencing reagents (containing buffers and nucleotides) across the wells of the plate. The four DNA nucleotides were added sequentially in a fixed order across the PicoTiterPlate device during a sequencing run. During the nucleotide flow, millions of copies of DNA bound to each of the beads were sequenced in parallel. When a nucleotide complementary to the template strand was added into a well, the polymerase extended the existing DNA strand by adding nucleotide(s). Addition of one (or more) nucleotide(s) generated a light signal that was recorded by the CCD camera in the instrument. This technique was based on sequencing-by-synthesis and called pyrosequencing. The signal strength was proportional to the number of nucleotides; for example, homopolymer stretches, incorporated in a single nucleotide flow, generated a greater signal than single nucleotides. However, the signal strength for homopolymer stretches was linear only up to eight consecutive nucleotides, after which the signal fell off rapidly. Data were stored in standard flowgram format (SFF) files for downstream analysis.
== See also ==
DNA Sequencing
== Notes == | Wikipedia/454_Life_Sciences |
DeCS – Health Sciences Descriptors is a structured and trilingual thesaurus created by BIREME – Latin American and Caribbean Center on Health Sciences Information – in 1986 for indexing scientific journal articles, books, proceedings of congresses, technical reports and other types of materials, as well as for searching and recovering scientific information in LILACS, MEDLINE and other databases. In the VHL, Virtual Health Library, DeCS is the tool that permits the navigation between records and sources of information through controlled concepts and organized in Portuguese, Spanish and English.
It was developed from MeSH – Medical Subject Headings from the NLM – U.S. National Library of Medicine – in order to permit the use of common terminology for searching in three languages, providing a consistent and unique environment for information retrieval regardless of the language. In addition to the original MeSH terms, four specific areas were developed: Public Health (1986), Homeopathy (1991), Health Surveillance (2005), and Science and Health (2005).
The concepts that compose the DeCS vocabulary are organized in a hierarchical structure permitting searches in broader or more specific terms or all the terms that belong to a single hierarchy.
Its main purpose is to serve as a unique language for indexing and recovery of information among the components of the Latin American and Caribbean Health Sciences Information System, coordinated by BIREME and that encompasses 37 countries in Latin America and the Caribbean, permitting a uniform dialog between nearly 600 libraries.
DeCS participates in the unified terminology development project, UMLS – Unified Medical Language System of the NLM, with the responsibility of contributing with the terms in Portuguese and Spanish.
== References ==
== External links ==
DeCS – Health Sciences Descriptors
DeCS on BIREME's Wiki Archived 2016-03-04 at the Wayback Machine
BIREME – Latin American and Caribbean Center on Health Sciences Information
VHL Regional Portal – Virtual Health Library
NLM – U. S. National Library of Medicine
UMLS – Unified Medical Language System
LILACS Methodology | Wikipedia/Health_Sciences_Descriptors |
The World Health Organization (WHO) ranked the health systems of its 191 member states in its World Health Report 2000. It provided a framework and measurement approach to examine and compare aspects of health systems around the world. It developed a series of performance indicators to assess the overall level and distribution of health in the populations, and the responsiveness and financing of health care services. It was the organization's first ever analysis of the world's health systems.
== Ranking ==
== Methodology ==
The rankings are based on an index of five factors:
Health (50%) : disability-adjusted life expectancy
Overall or average : 25%
Distribution or equality : 25%
Responsiveness (25%) : speed of service, protection of privacy, and quality of amenities
Overall or average : 12.5%
Distribution or equality : 12.5%
Fair financial contribution : 25%
== Criticism ==
The WHO rankings are claimed to have been subject to many and varied criticisms since its publication. Concerns raised over the five factors considered, data sets used and comparison methodologies have led health bodies and political commentators in most of the countries on the list to question the efficacy of its results and validity of any conclusions drawn. Such criticisms of a broad endeavour by the WHO to rank all the world's healthcare systems must also however be understood in the context of a predisposition to analytical bias commensurate with an individual nation's demographics, socio-economics and politics. In considering such a disparate global spectrum, ranking criteria, methodology, results and conclusions will always be an area for contention.
In over a decade of discussion and controversy over the WHO Ranking of 2000, there is still no consensus about how an objective world health system ranking should be compiled. Indeed, the 2000 results have proved so controversial that the WHO declined to rank countries in their World Health Reports since 2000, but the debate still rages on. With burgeoning and ageing populations, spiralling costs and the recognition by most national governments that constant vigilance and periodic healthcare reform are necessary, the appetite for a means of measuring national performance in broader world contexts is ever increasing and all the more relevant. With this in mind, and in lieu of any further ranking information from the WHO since 2000, there are many analytical bodies now looking at national healthcare delivery in global contexts and publishing their findings. Bloomberg finds "the U.S. spends the most on health care on a relative cost basis with the worst outcome" and notes Cubans live longer than Americans, but Americans pay more than fourteen times as much for less effective health care. The Commonwealth Fund ranked seven developed countries on health care, the US ranked lowest (AU, CA, DE, NL, NZ, UK, US).
== See also ==
Health systems – explains in some depth the concept of healthcare and its delivery on national and international scales
International comparisons of health systems – a section of the above article specifically about international comparisons
Healthcare subjects – a list of subjects detailing the complexities behind global healthcare delivery
List of countries by quality of healthcare
== References ==
== External links ==
The World Health Organization's ranking of the world's health systems, by Rank | Wikipedia/WHO's_ranking_of_health_care_systems |
The following outline is provided as an overview of and topical guide to health sciences:
Health sciences – those sciences that focus on health, or health care, as core parts of their subject matter. Health sciences relate to multiple academic disciplines, including STEM disciplines and emerging patient safety disciplines (such as social care research).
== Medicine and its branches ==
Medicine is an applied science or practice of the diagnosis, treatment, and prevention of disease. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness. Below are some of the branches of medicine.
Anesthesiology is the brand of medicine that deals with life support and anesthesia during surgery.
Angiology deals with the diseases of the circulatory system.
Audiology focuses on preventing and curing hearing damage.
Bariatrics deals with the causes, prevention, and treatment of obesity.
Cardiology deals with disorders of the heart and the blood vessels.
Critical care medicine focuses on life support and the intensive care of the seriously ill.
Dentistry is the branch of medicine that consists of the study, diagnosis, prevention, and treatment of diseases, disorders, and conditions of the oral cavity, commonly in the dentition but also the oral mucosa, and of adjacent and related structures and tissues, particularly in the maxillofacial (jaw and facial) area.
Dermatology deals with the skin, its structure, functions, and diseases.
Emergency medicine focuses on care provided in the emergency department.
Endocrinology deals with disorders of the endocrine system.
Family medicine is a medical specialty devoted to comprehensive health care for people of all ages.
Gastroenterology deals with the study and care of the digestive system.
General Practice (often called Family Medicine) is a branch of medicine that specializes in primary care.
Geriatrics is the branch of medicine that deals with the general health and well-being of the elderly.
Gynecology deals with the health of the female reproductive systems and the breasts.
Hematology deals with the blood and the circulatory system.
Hepatology deals with the liver, gallbladder and the biliary system.
Infectious disease is a branch of medicine that deals with the diagnosis and management of infectious disease, especially for complex cases and immunocompromised patients.
Clinical immunology is the study of the human immune system.
Kinesiology is the scientific study of human or non-human body movement.
Laboratory medicine deals with diagnostic laboratory examinations and tests and their interpretation what makes in a medical laboratory.
Medical physics is the branch of medicine and science that deals with applications of physics concepts, theories, and methods to medicine or health care.
Neurology deals with the brain and the nervous system.
Nephrology is the branch of medicine which deals with the kidneys.
Oncology is the branch of medicine that studies of cancer.
Ophthalmology deals with the eyes.
Orthopedics is a branch of surgery concerned with conditions involving the musculoskeletal system
Otolaryngology deals the ears, nose and throat.
Pathology is the study of diseases, and the causes, processes, nature, and development of the disease.
Pediatrics is the branch of medicine that deals with the general health and well-being of children.
Pharmacy is the art and practice of preparing, preserving, compounding, and dispensing medical drugs
Pharmacology is study and practical application of preparation, use, and effects of drugs and synthetic medicines.
Public health and preventive medicine is the branch of medicine concerned with the health of populations.
Pulmonology is the branch of medicine that deals with the respiratory system.
Psychiatry deals with the study, diagnosis, treatment, and prevention of mental disorders.
Clinical psychology is a health discipline concerned with the biopsychosocial study of the mind, brain, behavior and the diagnosis, treatment and prevention of psychological disorders.
Radiology is the branch of medicine that employs medical imaging to diagnose and treat disease.
Rheumatology deals with the diagnosis and treatment of rheumatic diseases.
Splanchnology deals with visceral organs.
Surgery is the branch of medicine that uses operative techniques to investigate or treat both disease and injury, or to help improve bodily function or appearance.
Urology is the branch of medicine that deals with the urinary system and the male reproductive system.
Veterinary medicine is the branch of medicine that deals with the prevention, diagnosis, and treatment of disease, disorder, and injury in nonhuman/animals.
== History of health sciences ==
History of medicine
== General health sciences concepts ==
Disease
Healing
Health
Health care
Doctor
Dentist
Physician
Surgeon
Veterinarian
Hospital
Nurse
Medication
Operation
== Diagnostic methods ==
Physical examination
Auscultation
Percussion
Medical history
Medical imaging
X-ray
CT scan
PET scan
MRI
SPECT (Single-photon emission computed tomography)
Ultrasound
Microscopy
Phlebotomy
Rating scales
== See also ==
Academic health science centre
Biomedical sciences
Health economics
List of health sciences topics
List of life sciences
== External links ==
Links to Health Professions websites
National Institute of Environmental Health Sciences
The US National Library of Medicine | Wikipedia/Healthcare_science |
Vascular disease is a class of diseases of the vessels of the circulatory system in the body, including blood vessels – the arteries and veins, and the lymphatic vessels. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood and lymph vessels can cause a range of health problems that can sometimes become severe, and fatal. Coronary heart disease for example, is the leading cause of death for men and women in the United States.
== Types ==
There are several types of vascular disease, including venous diseases, and arterial diseases, and signs and symptoms vary depending on the disease. Those of the arterial system are associated with blood supply to tissues and its obstruction due to blockages or narrowing. In the venous system disorders are often caused by a slow return of blood due to insufficient valves, or to a blood clot.
=== Venous disease ===
Most disorders of the veins involve obstruction such as a thrombus or insufficiency of the valves, or both of these. Other conditions may be due to inflammation.
==== Phlebitis ====
Phlebitis is the inflammation of a vein. It is usually accompanied by a blood clot when it is known as thrombophlebitis. When the affected vein is a superficial vein in the leg, it is known as superficial thrombophlebitis, and unlike deep vein thrombosis there is little risk of the clot breaking off as an embolus.
==== Venous insufficiency ====
Venous insufficiency is the most common disorder of the venous system, and is usually manifested as either spider veins or varicose veins. Several treatments are available including endovenous thermal ablation (using radiofrequency or laser energy), vein stripping, ambulatory phlebectomy, foam sclerotherapy, laser, or compression.
Postphlebitic syndrome is venous insufficiency that develops following deep vein thrombosis.
==== Venous thrombosis ====
Venous thrombosis is the formation of a thrombus (blood clot) in a vein. This most commonly affects a deep vein known as deep vein thrombosis (DVT). DVT usually occurs in the veins of the legs, although it can also occur in the veins of the arms. Immobility, active cancer, obesity, traumatic damage and congenital disorders that make clots more likely are all risk factors for deep vein thrombosis. It can cause the affected limb to swell, and cause pain and an overlying skin rash. In the worst case, a deep vein thrombosis can extend, or a part of a clot can break off as an embolus and lodge in a pulmonary artery in the lungs, known as a pulmonary embolism.The decision to treat deep vein thrombosis depends on its size, a person's symptoms, and their risk factors. It generally involves anticoagulation to prevents clots or to reduce the size of the clot. Intermittent pneumatic compression is a method used to improve venous circulation in cases of edema or in those at risk from a deep vein thrombosis.
A clot can also form in a superficial vein (superficial venous thrombosis) which is normally not clinically significant, but the thrombus can migrate into the deep venous system where it can also give rise to a pulmonary embolism.
==== Portal hypertension ====
The portal vein also known as the hepatic portal vein carries blood drained from most of the gastrointestinal tract to the liver. Portal hypertension is mainly caused by cirrhosis of the liver. Other causes can include an obstructing clot in a hepatic vein (Budd Chiari syndrome) or compression from tumors or tuberculosis lesions. When the pressure increases in the portal vein, a collateral circulation develops, causing visible veins such as esophageal varices.
==== Vascular anomalies ====
A vascular anomaly can be either a vascular tumor or a birthmark, or a vascular malformation.
In a tumor such as infantile hemangioma the mass is soft, and easily compressed, and their coloring is due to the dilated anomalous involved veins. They are most commonly found in the head and neck. Venous malformations are the type of vascular malformation that involves the veins. They can often extend deeper from their surface appearance, reaching underlying muscle or bone. In the neck they may extend into the lining of the mouth cavity or into the salivary glands. They are the most common of the vascular malformations. A severe venous malformation can involve the lymph vessels as a lymphaticovenous malformation.
=== Arterial disease ===
Coronary artery disease – the most common of the cardiovascular diseases, types include angina, and myocardial infarction
Carotid artery stenosis – any narrowing of the carotid arteries
Peripheral artery disease – occurs when atheromatous plaques build up in the arteries that supply blood to the arms and legs, causing the arteries to narrow or become blocked.
Erythromelalgia - a rare peripheral vascular disease with symptoms that include burning pain, increased temperature, erythema and swelling that generally affect the hands and feet.
Renal artery stenosis - the narrowing of renal arteries that carry blood to the kidneys from the aorta.
Buerger's disease – inflammation and swelling in small blood vessels, causing the vessels to narrow or become blocked by blood clots.
Raynaud syndrome – a peripheral vascular disorder that causes constriction of the peripheral blood vessels in the fingers and toes when a person is cold or experiencing stress.
Disseminated intravascular coagulation – a widespread activation of clotting in the smaller blood vessels.
Cerebrovascular disease – a group of vascular diseases that affect brain function, most commonly a stroke.
Vasculitis - inflammation of blood vessels, either arteries or veins
=== Lymphatic disease ===
Lymphangitis
== Mechanism ==
Vascular disease is a pathological state of large and medium muscular arteries and is triggered by endothelial cell dysfunction.
Because of factors like pathogens, oxidized LDL particles and other inflammatory stimuli endothelial cells become active.
The process causes thickening of the vessel wall, forming a plaque that consists of proliferating smooth muscle cells, macrophages and lymphocytes.
The plaque results in restricted blood flow, decreasing the amount of oxygen and nutrients that reach certain organs.
This plaque can also rupture, causing the formation of clots.
== Diagnosis ==
Diagnosing vascular disease can be complex due to the variety of symptoms vascular diseases can cause. Reviewing a patient's family history and conducting a physical examination are important steps in making a diagnosis. Physical exams may differ depending on the type of vascular disease suspected. For example, in the case of a peripheral vascular disease, a physical exam consists of checking blood flow in a patient's legs.
== Treatment ==
Treatment varies based on the type of vascular disease being treated. In treating renal artery disease, a 2014 study indicates that balloon angioplasty can improve diastolic blood pressure and potentially reduce antihypertensive drug requirements. In the case of peripheral artery disease, treatment to prevent complications is important; without treatment, sores or gangrene (tissue death) may occur.
More generally, treatments for vascular disease may include:
Lowering cholesterol levels
Lowering blood pressure
Lowering blood glucose
Changes in diet
Increasing physical activity (as recommended by a healthcare provider)
Weight loss
Quitting smoking
Stress reduction
== References ==
== Further reading ==
"The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials". www.crd.york.ac.uk. Retrieved 2015-06-23.
== External links == | Wikipedia/Vascular_disease |
Tropical diseases are diseases that are prevalent in or unique to tropical and subtropical regions. The diseases are less prevalent in temperate climates, due in part to the occurrence of a cold season, which controls the insect population by forcing hibernation. However, many were present in northern Europe and northern America in the 17th and 18th centuries before modern understanding of disease causation. The initial impetus for tropical medicine was to protect the health of colonial settlers, notably in India under the British Raj. Insects such as mosquitoes and flies are by far the most common disease carrier, or vector. These insects may carry a parasite, bacterium or virus that is infectious to humans and animals. Most often disease is transmitted by an insect bite, which causes transmission of the infectious agent through subcutaneous blood exchange. Vaccines are not available for most of the diseases listed here, and many do not have cures.
Human exploration of tropical rainforests, deforestation, rising immigration and increased international air travel and other tourism to tropical regions has led to an increased incidence of such diseases to non-tropical countries. Of particular concern is the habitat loss of reservoir host species.
== Health programmes ==
In 1975 the Special Programme for Research and Training in Tropical Diseases (TDR) was established to focus on neglected infectious diseases which disproportionately affect poor and marginalized populations in developing regions of Africa, Asia, Central America and North South America. It was established at the World Health Organization, which is the executing agency, and is co-sponsored by the United Nations Children's Fund, United Nations Development Programme, the World Bank and the World Health Organization.
TDR's vision is to foster an effective global research effort on infectious diseases of poverty in which disease endemic countries play a pivotal role. It has a dual mission of developing new tools and strategies against these diseases, and to develop the research and leadership capacity in the countries where the diseases occur. The TDR secretariat is based in Geneva, Switzerland, but the work is conducted throughout the world through many partners and funded grants.
Some examples of work include helping to develop new treatments for diseases, such as ivermectin for onchocerciasis (river blindness); showing how packaging can improve use of artemesinin-combination treatment (ACT) for malaria; demonstrating the effectiveness of bednets to prevent mosquito bites and malaria; and documenting how community-based and community-led programmes increases distribution of multiple treatments. TDR history
The current TDR disease portfolio includes the following entries:
† Although leprosy and tuberculosis are not exclusively tropical diseases, their high incidence in the tropics justifies their inclusion.
‡ People living with HIV are 19 (15–22) times more likely to develop active TB disease than people without HIV.
== Other neglected tropical diseases ==
Additional neglected tropical diseases include:
Some tropical diseases are very rare, but may occur in sudden epidemics, such as the Ebola hemorrhagic fever, Lassa fever and the Marburg virus. There are hundreds of different tropical diseases which are less known or rarer, but that, nonetheless, have importance for public health.
== Relation of climate to tropical diseases ==
The so-called "exotic" diseases in the tropics have long been noted both by travelers, explorers, etc., as well as by physicians. One obvious reason is that the hot climate present during all the year and the larger volume of rains directly affect the formation of breeding grounds, the larger number and variety of natural reservoirs and animal diseases that can be transmitted to humans (zoonosis), the largest number of possible insect vectors of diseases. It is possible also that higher temperatures may favor the replication of pathogenic agents both inside and outside biological organisms. Socio-economic factors may be also in operation, since most of the poorest nations of the world are in the tropics. Tropical countries like Brazil, which have improved their socio-economic situation and invested in hygiene, public health and the combat of transmissible diseases have achieved dramatic results in relation to the elimination or decrease of many endemic tropical diseases in their territory.
Climate change, global warming caused by the greenhouse effect, and the resulting increase in global temperatures, are possibly causing tropical diseases and vectors to spread to higher altitudes in mountainous regions, and to higher latitudes that were previously spared, such as the Southern United States, the Mediterranean area, etc. For example, in the Monteverde cloud forest of Costa Rica, global warming enabled Chytridiomycosis, a tropical disease, to flourish and thus force into decline amphibian populations of the Monteverde Harlequin frog. Here, global warming raised the heights of orographic cloud formation, and thus produced cloud cover that would facilitate optimum growth conditions for the implicated pathogen, B. dendrobatidis.
=== Role of human activities in the spread of tropical diseases ===
Human activities, particularly those driving climate change, are significantly influencing the spread and geographical range of tropical diseases. The burning of fossil fuels, deforestation, industrial agriculture, and urbanization release large amounts of greenhouse gases into the atmosphere, raising global temperatures and altering weather patterns. These environmental changes, such as increased rainfall, higher temperatures, and more frequent extreme weather events, create more favorable conditions for disease vectors like mosquitoes, which transmit diseases such as malaria, dengue, and Zika. In many cases, this has expanded the reach of tropical diseases into regions that were previously unaffected, including higher altitudes and temperate zones. Additionally, human-driven habitat destruction, such as the clearing of forests and wetlands, disrupts natural reservoirs and increases human-wildlife contact, further elevating the risk of zoonotic diseases crossing into human populations. As climate change continues, these activities will likely exacerbate the public health burden, especially in low-income regions that are most vulnerable to both the impacts of climate change and the diseases it helps spread.
== Prevention and treatment ==
=== Vector-borne diseases ===
Vectors are living organisms that pass disease between humans or from animal to human. The vector carrying the highest number of diseases is the mosquito, which is responsible for the tropical diseases dengue and malaria. Many different approaches have been taken to treat and prevent these diseases. NIH-funded research has produced genetically modify mosquitoes that are unable to spread diseases such as malaria. An issue with this approach is global accessibility to genetic engineering technology; Approximately 50% of scientists in the field do not have access to information on genetically modified mosquito trials being conducted.
Other prevention methods include:
Draining wetlands to reduce populations of insects and other vectors, or introducing natural predators of the vectors.
The application of insecticides and/or insect repellents to strategic surfaces such as clothing, skin, buildings, insect habitats, and bed nets.
The use of a mosquito net over a bed (also known as a "bed net") to reduce nighttime transmission, since certain species of tropical mosquitoes feed mainly at night.
=== Community approaches ===
Assisting with economic development in endemic regions can contribute to prevention and treatment of tropical diseases. For example, microloans enable communities to invest in health programs that lead to more effective disease treatment and prevention technology.
Educational campaigns can aid in the prevention of various diseases. Educating children about how diseases spread and how they can be prevented has proven to be effective in practicing preventative measures. Educational campaigns can yield significant benefits at low costs.
=== Innovative approaches ===
Recent advancements in vector control technologies are proving effective in reducing the transmission of mosquito-borne diseases like malaria, dengue, and Zika. Genetically modified (GM) mosquitoes, such as Oxitec's mosquitoes, which prevent females from surviving to adulthood, have demonstrated over a 90% reduction in mosquito populations in field trials in Brazil.
Another promising approach is the use of Wolbachia bacteria, which renders mosquitoes resistant to the dengue virus. A trial in Yogyakarta, Indonesia, showed a 77% reduction in symptomatic dengue cases in areas with Wolbachia-infected mosquitoes.
Additionally, integrated vector management (IVM), which combines biological controls, insecticides, and public education, has proven successful in reducing the transmission of arboviruses. These strategies offer more sustainable and eco-friendly solutions for controlling mosquito populations and preventing disease spread.
=== Other approaches ===
Use of water wells, and/or water filtration, water filters, or water treatment with water tablets to produce drinking water free of parasites.
Sanitation to prevent transmission through human waste.
Development and use of vaccines to promote disease immunity.
Pharmacologic treatment (to treat disease after infection or infestation).
== See also ==
Hospital for Tropical Diseases
Tropical medicine
Infectious disease
Neglected diseases
List of epidemics
Waterborne diseases
Globalization and disease
== References ==
== Further reading ==
=== Books ===
TDR at a glance – fostering an effective global research effort on diseases of poverty
Le TDR en un coup d’oeilLe TDR en un coup d’oeil – favoriser un eff ort mondial de recherche eff icace sur les maladies liées à la pauvreté
TDR annual report – 2009
Monitoring and evaluation tool kit for indoor residual spraying
Indicators for monitoring and evaluation of the kala-azar elimination programme
Malaria Rapid Diagnostic Test Performance – results of WHO product testing of malaria RDTs: Round 2- 2009
Quality Practices in Basic Biomedical Research (QPBR) training manual: Trainer
Quality Practices in Basic Biomedical Research (QPBR) training manual: Trainee
Progress and prospects for the use of genetically modified mosquitoes to inhibit disease transmission
Use of Influenza Rapid Diagnostic Tests
Manson's Tropical Diseases
Mandell's Principles and Practice of Infectious Diseases or this site
=== Journals ===
American Journal of Tropical Medicine and Hygiene
Japanese Journal of Tropical Medicine and Hygiene
Tropical Medicine and International Health
The Southeast Asian Journal of Tropical Medicine and Public Health
Revista do Instituto de Medicina Tropical de São Paulo
Revista da Sociedade Brasileira de Medicina Tropical
Journal of Venomous Animals and Toxins including Tropical Diseases
=== Websites ===
Special Programme for Research and Training in Tropical Diseases -TDR
GIDEON-Global Infectious Disease Epidemiology Network
== External links ==
WHO Neglected Tropical Diseases
WHO Operational research in tropical and other communicable diseases
European Bioinformatics Institute
open source drug discovery
Drugs for Neglected Diseases Initiative
Tropical diseases from Maya Paradise, The Guatemala Information Web Site
American Society for Tropical Medicine and Hygiene
Treating Tropical Diseases U.S. Food and Drug Administration
Travelers' Health – National Center for Infectious Diseases – Centers for Disease Control and Prevention
Tropicology Library. In Portuguese.
'Conquest and Disease or Colonisation and Health', lecture by Professor Frank Cox on the history of tropical disease, given at Gresham College, 17 September 2007 (available for download as video and audio files, as well as a text file).
Thomas Nutman (December 28, 2007). "Neglected Tropical Diseases Burden Those Overseas, But Travelers Also At Risk". ScienceDaily. NIH/National Institute of Allergy and Infectious Diseases. Retrieved 2025-05-22. | Wikipedia/Tropical_diseases |
Clinical epidemiology is a subfield of epidemiology specifically focused on issues relevant to clinical medicine. The term was first introduced by virologist John R. Paul in his presidential address to the American Society for Clinical Investigation in 1938. It is sometimes referred to as "the basic science of clinical medicine".
== Definition ==
When he coined the term "clinical epidemiology" in 1938, John R. Paul defined it as "a marriage between quantitative concepts used by epidemiologists to study disease in populations and decision-making in the individual case which is the daily fare of clinical medicine". According to Stephenson & Babiker (2000), "Clinical epidemiology can be defined as the investigation and control of the distribution and determinants of disease." Walter O. Spitzer has highlighted the ways in which the field of clinical epidemiology is not clearly defined. However, he felt that, despite criticism of the term, it was a useful way to define a specific subfield of epidemiology. In contrast, John M. Last felt that the term was an oxymoron, and that its increasing popularity in many different medical schools was a serious problem.
Clinical epidemiology aims to optimise the diagnostic, treatment and prevention processes for an individual patient, based on an assessment of the diagnostic and treatment process using epidemiological research data. A central tenet of clinical epidemiology is that every clinical decision must be based on rigorously evidence-based science.
The objectives of clinical epidemiology are primarily to develop epidemiologically sound clinical guidelines and standards for diagnosis, disease progression, prognosis, treatment and prevention. The data obtained in epidemiological studies are also applicable for the epidemiological justification of preventive programmes for communicable and noncommunicable diseases.
There are various types of epidemiological studies in use: case-control studies, cohort studies, experimental controlled randomised trials (RCTs).
Experimentation, in general, is a general scientific method of testing causal hypotheses by means of an intervention (controlled influence) in the natural course of the phenomenon under study. In order to assess the result of the intervention, the experiment necessarily involves comparable groups - experimental and control, i.e. the study is controlled. The division of patients into groups should be done casually, by randomisation.
A key aspect of clinical epidemiology is the evaluation of the effectiveness of treatment and prevention medicines.
The effectiveness of preventive and curative medicines is divided into potential effectiveness (the maximum achievable effect of interventions at a given level of science) and real effectiveness (the effect that is available in practice).
== See also ==
Journal of Clinical Epidemiology
== References == | Wikipedia/Clinical_epidemiology |
Biomedical sciences are a set of sciences applying portions of natural science or formal science, or both, to develop knowledge, interventions, or technology that are of use in healthcare or public health. Such disciplines as medical microbiology, clinical virology, clinical epidemiology, genetic epidemiology, and biomedical engineering are medical sciences. In explaining physiological mechanisms operating in pathological processes, however, pathophysiology can be regarded as basic science.
Biomedical Sciences, as defined by the UK Quality Assurance Agency for Higher Education Benchmark Statement in 2015, includes those science disciplines whose primary focus is the biology of human health and disease and ranges from the generic study of biomedical sciences and human biology to more specialised subject areas such as pharmacology, human physiology and human nutrition. It is underpinned by relevant basic sciences including anatomy and physiology, cell biology, biochemistry, microbiology, genetics and molecular biology, pharmacology, immunology, mathematics and statistics, and bioinformatics. As such the biomedical sciences have a much wider range of academic and research activities and economic significance than that defined by hospital laboratory sciences. Biomedical Sciences are the major focus of bioscience research and funding in the 21st century.
== Roles within biomedical science ==
A sub-set of biomedical sciences is the science of clinical laboratory diagnosis. This is commonly referred to in the UK as 'biomedical science' or 'healthcare science'. There are at least 45 different specialisms within healthcare science, which are traditionally grouped into three main divisions:
specialisms involving life sciences
specialisms involving physiological science
specialisms involving medical physics or bioengineering
== Life sciences specialties ==
Molecular toxicology
Molecular pathology
Blood transfusion science
Cervical cytology
Clinical biochemistry
Clinical embryology
Clinical immunology
Clinical pharmacology and therapeutics
Electron microscopy
External quality assurance
Haematology
Haemostasis and thrombosis
Histocompatibility and immunogenetics
Histopathology and cytopathology
Molecular genetics and cytogenetics
Molecular biology and cell biology
Microbiology including mycology
Bacteriology
Tropical diseases
Phlebotomy
Tissue banking/transplant
Virology
== Physiological science specialisms ==
== Physics and bioengineering specialisms ==
== Biomedical science in the United Kingdom ==
The healthcare science workforce is an important part of the UK's National Health Service. While people working in healthcare science are only 5% of the staff of the NHS, 80% of all diagnoses can be attributed to their work.
The volume of specialist healthcare science work is a significant part of the work of the NHS. Every year, NHS healthcare scientists carry out:
nearly 1 billion pathology laboratory tests
more than 12 million physiological tests
support for 1.5 million fractions of radiotherapy
The four governments of the UK have recognised the importance of healthcare science to the NHS, introducing the Modernising Scientific Careers initiative to make certain that the education and training for healthcare scientists ensures there is the flexibility to meet patient needs while keeping up to date with scientific developments.
Graduates of an accredited biomedical science degree programme can also apply for the NHS' Scientist training programme, which gives successful applicants an opportunity to work in a clinical setting whilst also studying towards an MSc or Doctoral qualification.
== Biomedical Science in the 20th century ==
At this point in history the field of medicine was the most prevalent sub field of biomedical science, as several breakthroughs on how to treat diseases and help the immune system were made. As well as the birth of body augmentations.
=== 1910s ===
In 1912, the Institute of Biomedical Science was founded in the United Kingdom. The institute is still standing today and still regularly publishes works in the major breakthroughs in disease treatments and other breakthroughs in the field 117 years later. The IBMS today represents approximately 20,000 members employed mainly in National Health Service and private laboratories.
=== 1920s ===
In 1928, British Scientist Alexander Fleming discovered the first antibiotic penicillin. This was a huge breakthrough in biomedical science because it allowed for the treatment of bacterial infections.
In 1926, the first artificial pacemaker was made by Australian physician Dr. Mark C. Lidwell. This portable machine was plugged into a lighting point. One pole was applied to a skin pad soaked with strong salt solution, while the other consisted of a needle insulated up to the point and was plunged into the appropriate cardiac chamber and the machine started. A switch was incorporated to change the polarity. The pacemaker rate ranged from about 80 to 120 pulses per minute and the voltage also variable from 1.5 to 120 volts.
=== 1930s ===
The 1930s was a huge era for biomedical research, as this was the era where antibiotics became more widespread and vaccines started to be developed. In 1935, the idea of a polio vaccine was introduced by Dr. Maurice Brodie. Brodie prepared a died poliomyelitis vaccine, which he then tested on chimpanzees, himself, and several children. Brodie's vaccine trials went poorly since the polio-virus became active in many of the human test subjects. Many subjects had fatal side effects, paralyzing, and causing death.
=== 1940s ===
During and after World War II, the field of biomedical science saw a new age of technology and treatment methods. For instance in 1941 the first hormonal treatment for prostate cancer was implemented by Urologist and cancer researcher Charles B. Huggins. Huggins discovered that if you remove the testicles from a man with prostate cancer, the cancer had nowhere to spread, and nothing to feed on thus putting the subject into remission. This advancement lead to the development of hormonal blocking drugs, which is less invasive and still used today. At the tail end of this decade, the first bone marrow transplant was done on a mouse in 1949. The surgery was conducted by Dr. Leon O. Jacobson, he discovered that he could transplant bone marrow and spleen tissues in a mouse that had both no bone marrow and a destroyed spleen. The procedure is still used in modern medicine today and is responsible for saving countless lives.
=== 1950s ===
In the 1950s, we saw innovation in technology across all fields, but most importantly there were many breakthroughs which led to modern medicine. On 6 March 1953, Dr. Jonas Salk announced the completion of the first successful killed-virus Polio vaccine. The vaccine was tested on about 1.6 million Canadian, American, and Finnish children in 1954. The vaccine was announced as safe on 12 April 1955.
== See also ==
Biomedical research institution Austral University Hospital
== References ==
== External links ==
Extraordinary You: Case studies of Healthcare scientists in the UK's National Health Service
National Institute of Environmental Health Sciences
The US National Library of Medicine
National Health Service | Wikipedia/Biomedical_science |
This list of life sciences comprises the branches of science that involve the scientific study of life – such as microorganisms, plants, and animals including human beings. This science is one of the two major branches of natural science, the other being physical science, which is concerned with non-living matter. Biology is the overall natural science that studies life, with the other life sciences as its sub-disciplines.
Some life sciences focus on a specific type of organism. For example, zoology is the study of animals, while botany is the study of plants. Other life sciences focus on aspects common to all or many life forms, such as anatomy and genetics. Some focus on the micro-scale (e.g. molecular biology, biochemistry) other on larger scales (e.g. cytology, immunology, ethology, pharmacy, ecology). Another major branch of life sciences involves understanding the mind – neuroscience. Life sciences discoveries are helpful in improving the quality and standard of life and have applications in health, agriculture, medicine, and the pharmaceutical and food science industries. For example, it has provided information on certain diseases which has overall aided in the understanding of human health.
== Basic life science branches ==
Biology – scientific study of life
Anatomy – study of form and function, in plants, animals, and other organisms
Histology – the study of tissues
Neuroscience – the study of the nervous system
Astrobiology – the study of the formation and presence of life in the universe
Biotechnology – study of combination of both the living organism and technology
Biochemistry – the study of the chemical reactions required for life to exist and function, usually focused on the cellular level
Quantum biology – the study of quantum phenomena in organisms
Bioinformatics – developing of methods or software tools for storing, retrieving, organizing and analyzing biological data to generate useful biological knowledge
Biophysics – study of biological processes by applying the theories and methods that have been traditionally used in the physical sciences
Biomechanics – the study of the mechanics of living beings
Botany – study of plants
Agrostology – the study of grasses and grass-like species
Phycology – the study of algae
Cell biology (cytology) – study of the cell as a complete unit, and the molecular and chemical interactions that occur within a living cell
Developmental biology – the study of the processes through which an organism forms, from zygote to full structure
Ecology – study of the interactions of living organisms with one another and with the non-living elements of their environment
Enzymology – study of enzymes
Evolutionary biology – study of the origin and descent of species over time
Evolutionary developmental biology – the study of the evolution of development including its molecular control
Genetics – the study of genes and heredity
Immunology – the study of the immune system
Marine biology – the study of ocean organisms
Biological oceanography – the study of life in the oceans and their interaction with the environment
Microbiology – the study of microscopic organisms (microorganisms) and their interactions with other living organisms
Aerobiology – study of the movement and transportation of microorganisms in the air
Bacteriology – study of bacteria
Virology – study of viruses and virus-like agents
Molecular biology – the study of biology and biological functions at the molecular level, some cross over with biochemistry, genetics, and microbiology
Structural biology – a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macro-molecules
Mycology – the study of fungi
Paleontology – the study of prehistoric organisms
Parasitology – the study of parasites, their hosts, and the relationship between them
Pathology – study of the causes and effects of disease or injury
Human biology – the biological study of human beings
Pharmacology – study of drug action
Biological (or physical) anthropology – the study of humans, non-human primates, and hominids
Biolinguistics – the study of the biology and evolution of language
Physiology – the study of the functioning of living organisms and the organs and parts of living organisms
Population biology – the study of groups of conspecific organisms
Population dynamics – the study of short-term and long-term changes in the size and age composition of populations, and the biological and environmental processes influencing those changes. Population dynamics deals with the way populations are affected by birth and death rates, and by immigration and emigration, and studies topics such as ageing populations or population decline.
Synthetic biology – the design and construction of new biological entities such as enzymes, genetic circuits and cells, or the redesign of existing biological systems
Systems biology – the study of the integration and dependencies of various components within a biological system, with particular focus upon the role of metabolic pathways and cell-signaling strategies in physiology
Theoretical biology – use of abstractions and mathematical models to study biological phenomena
Toxicology – the study of poisons
Zoology – the study of (generally non-human) animals
Ethology – the study of animal behavior
== Applied life science branches and derived concepts ==
Agriculture – science and practice of cultivating plants and livestock
Agronomy – science of cultivating plants for resources
Biocomputers – systems of biologically derived molecules, such as DNA and proteins, are used to perform computational calculations involving storing, retrieving, and processing data. The development of biological computing has been made possible by the expanding new science of nanobiotechnology.
Biocontrol – bioeffector-method of controlling pests (including insects, mites, weeds and plant diseases) using other living organisms.
Bioengineering – study of biology through the means of engineering with an emphasis on applied knowledge and especially related to biotechnology
Bioelectronics – field at the convergence of electronics and biological sciences. The electrical state of biological matter significantly affects its structure and function, compare for instance the membrane potential, the signal transduction by neurons, the isoelectric point (IEP) and so on. Micro- and nano-electronic components and devices have increasingly been combined with biological systems like medical implants, biosensors, lab-on-a-chip devices etc. causing the emergence of this new scientific field.
Biomaterials – any matter, surface, or construct that interacts with biological systems. As a science, biomaterials is about fifty years old. The study of biomaterials is called biomaterials science. It has experienced steady and strong growth over its history, with many companies investing large amounts of money into the development of new products. Biomaterials science encompasses elements of medicine, biology, chemistry, tissue engineering and materials science.
Biomedical science – healthcare science, also known as biomedical science, is a set of applied sciences applying portions of natural science or formal science, or both, to develop knowledge, interventions, or technology of use in healthcare or public health. Such disciplines as medical microbiology, clinical virology, clinical epidemiology, genetic epidemiology and pathophysiology are medical sciences.
Biomonitoring – measurement of the body burden of toxic chemical compounds, elements, or their metabolites, in biological substances. Often, these measurements are done in blood and urine.
Biopolymer – polymers produced by living organisms; in other words, they are polymeric biomolecules. Since they are polymers, biopolymers contain monomeric units that are covalently bonded to form larger structures. There are three main classes of biopolymers, classified according to the monomeric units used and the structure of the biopolymer formed: polynucleotides (RNA and DNA), which are long polymers composed of 13 or more nucleotide monomers; polypeptides, which are short polymers of amino acids; and polysaccharides, which are often linear bonded polymeric carbohydrate structures.
Biotechnology – manipulation of living matter, including genetic modification and synthetic biology
Conservation biology – the management of nature and of Earth's biodiversity with the aim of protecting species, their habitats, and ecosystems from excessive rates of extinction and the erosion of biotic interactions. It is an interdisciplinary subject drawing on natural and social sciences, and the practice of natural resource management.
Environmental health – multidisciplinary field concerned with environmental epidemiology, toxicology, and exposure science.
Fermentation technology – study of use of microorganisms for industrial manufacturing of various products like vitamins, amino acids, antibiotics, beer, wine, etc.
Food science – applied science devoted to the study of food. Activities of food scientists include the development of new food products, design of processes to produce and conserve these foods, choice of packaging materials, shelf-life studies, study of the effects of food on the human body, sensory evaluation of products using panels or potential consumers, as well as microbiological, physical (texture and rheology) and chemical testing.
Genomics – application of recombinant DNA, DNA sequencing methods, and bioinformatics to sequence, assemble, and analyze the function and structure of genomes (the complete set of DNA within a single cell of an organism). The field includes efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping. The field also includes studies of intragenomic phenomena such as heterosis, epistasis, pleiotropy and other interactions between loci and alleles within the genome. In contrast, the investigation of the roles and functions of single genes is a primary focus of molecular biology or genetics and is a common topic of modern medical and biological research. Research of single genes does not fall into the definition of genomics unless the aim of this genetic, pathway, and functional information analysis is to elucidate its effect on, place in, and response to the entire genome's networks.
Health sciences – sciences which focus on health, or health care, as core parts of their subject matter. These two subject matters relate to multiple academic disciplines, both STEM disciplines, as well as emerging patient safety disciplines (such as social care research), and are both relevant to current health science knowledge.
Medical devices – A medical device is an instrument, apparatus, implant, in vitro reagent, or similar or related article that is used to diagnose, prevent, or treat disease or other conditions, and does not achieve its purposes through chemical action within or on the body (which would make it a drug). Whereas medicinal products (also called pharmaceuticals) achieve their principal action by pharmacological, metabolic or immunological means, medical devices act by other means like physical, mechanical, or thermal means.
Medical imaging – the technique and process used to create images of the human body (or parts and function thereof) for clinical or physiological research purposes
Immunotherapy – the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies.
Kinesiology – scientific study of human movement. Kinesiology, also known as human kinetics, addresses physiological, mechanical, and psychological mechanisms. Applications of kinesiology to human health include: biomechanics and orthopedics; strength and conditioning; sport psychology; methods of rehabilitation, such as physical and occupational therapy; and sport and exercise. Individuals who have earned degrees in kinesiology can work in research, the fitness industry, clinical settings, and in industrial environments. Studies of human and animal motion include measures from motion tracking systems, electrophysiology of muscle and brain activity, various methods for monitoring physiological function, and other behavioral and cognitive research techniques.
Optogenetics – a neuromodulation technique employed in neuroscience that uses a combination of techniques from optics and genetics to control and monitor the activities of individual neurons in living tissue—even within freely-moving animals—and to precisely measure the effects of those manipulations in real-time. The key reagents used in optogenetics are light-sensitive proteins. Spatially-precise neuronal control is achieved using optogenetic actuators like channelrhodopsin, halorhodopsin, and archaerhodopsin, while temporally-precise recordings can be made with the help of optogenetic sensors like Clomeleon, Mermaid, and SuperClomeleon.
Pharmacogenomics – field of science and technology that analyses how genetic makeup affects an individual's response to drugs. Pharmacogenomics (a portmanteau of pharmacology and genomics) deals with the influence of genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms with a drug's efficacy or toxicity.
Pharmacology – branch of medicine and biology concerned with the study of drug action, where a drug can be broadly defined as any human-made, natural, or endogenous (within the body) molecule which exerts a biochemical and/or physiological effect on the cell, tissue, organ, or organism. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals.
Proteomics – the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The proteome is the entire set of proteins, produced or modified by an organism or system. This varies with time and distinct requirements, or stresses, that a cell or organism undergoes.
== See also ==
Outline of biology
Divisions of pharmacology
Control theory
== References ==
== Further reading ==
Magner, Lois N. (2002). A history of the life sciences (Rev. and expanded 3rd ed.). New York: M. Dekker. ISBN 0824708245. | Wikipedia/Life_sciences |
Examples of health care systems of the world, sorted by continent, are as follows.
== Classification ==
Following sources of financing of healthcare systems can be categorized:
Single-payer healthcare: government-funded healthcare is available to all citizens regardless of their income or employment status. Some countries may provide healthcare to non-citizen residents, while some may require them to buy private insurance
Public insurance: In some countries workers have social insurance. Usually government withholds part of their wage, which is divided between employee and employer. People who are retired, unemployed or in education also have the right to healthcare paid by government but sometimes need to register for it manually.
Private insurance: Operated by private insurance companies where beneficiaries regularly pay a premium to be covered. Private insurance can be nonprofit or for-profit.
Out of pocket: Direct payment from the patient. This can be co-payments or co-insurance, or the full cost of the healthcare service.
Foreign aid
Countries in the table are categorized by the main system of financing their healthcare. Many countries in the world have multi-tiered healthcare systems with different ways of financing healthcare for different people and purposes.
== Table ==
Coverage: See row references, and the 2011 reference: "Estimate of health insurance coverage as a percentage of total population. Coverage includes affiliated members of health insurance or estimation of the population having free access to health care services provided by the State."
Asterisk (*) indicates "Healthcare in LOCATION" or "Health in LOCATION" links.
=== Notes ===
==== Japan ====
Population by coverage:
59% – employment-based insurance plans
27% – Citizen Health Insurance plans for nonemployed individuals
12.7% – Health Insurance for the Elderly plans
1.7% – Public Social Assistance Program, for impoverished people
Additionally 70% of people have supplementary private insurance.
==== Russia ====
Funded by federal, regional and municipal budgets and by separate employer's tax payments, but medical aid in state and municipal health establishments in all cases is available for free to all citizens, foreign permanent residents, foreign temporary residents, stateless persons and refugees regardless of their income or employment status.
==== United States ====
Single-payer for citizens over 65 (Medicare)
Public insurance for some low-income people (Medicaid)
Private health insurance
Out-of-pocket for uninsured population
== Africa ==
=== Algeria ===
When Algeria gained its independence from France in 1962, there were only around 300 doctors across the whole country and no proper system of healthcare. Over the next few decades, great progress was made in building up the health sector, with the training of doctors and the creation of many health facilities. Today, Algeria has an established network of hospitals (including university hospitals), clinics, medical centres and small health units or dispensaries. While equipment and medicines may not always be the latest available, staffing levels are high and the country has one of the best healthcare systems in Africa. Access to health care is enhanced by the requirement that doctors and dentists work in public health for at least five years. The government provides universal health care.
=== Cape Verde ===
Medical facilities in Cape Verde are limited, and some medicines are in short supply or unavailable. There are hospitals in Praia and Mindelo, with smaller medical facilities in other places. The islands of Brava and Santo Antão no longer have functioning airports so air evacuation in the event of a medical emergency is nearly impossible from these two islands. Brava also has limited inter-island ferry service.
=== Eritrea ===
Eritrea is one of the few countries to be on target to meet its Millennium Development Goal (MDG) targets for health. Researchers at the Overseas Development Institute have identified the high prioritisation of health and education both within the government and amongst Eritreans at home and abroad. Innovative multi-sectoral approaches to health were also identified with the success. About one-third of the population lives in extreme poverty, and more than half survives on less than US$1 per day. Health care and welfare resources generally are believed to be poor, although reliable information about conditions is often difficult to obtain. In 2001, the most recent year for which figures are available, the Eritrean government spent 5.7 percent of gross domestic product on national health accounts. The World Health Organization (WHO) estimated that in 2004 there were only three physicians per 100,000 people in Eritrea. The two-year war with Ethiopia, coming on the heels of a 30-year struggle for independence, negatively affected the health sector and the general welfare. The rate of prevalence of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), in Eritrea is believed to be at 0.7%(2012)which is reasonably low. In the decade since 1995, impressive results have been achieved in lowering maternal and child mortality rates and in immunizing children against childhood diseases. In 2008 average life expectancy was slightly less than 63 years, according to the WHO. Immunisation and child nutrition has been tackled by working closely with schools in a multi-sectoral approach; the number of children vaccinated against measles almost doubled in seven years, from 40.7% to 78.5% and the underweight prevalence among children decreased by 12% in 1995–2002 (severe underweight prevalence by 28%). This has helped to some small extent even out rural-urban and rich-poor inequity in health.
=== Ethiopia ===
Throughout the 1990s, the government, as part of its reconstruction program, devoted ever-increasing amounts of funding to the social and health sectors, which brought corresponding improvements in school enrollments, adult literacy, and infant mortality rates. These expenditures stagnated or declined during the 1998–2000 war with Eritrea, but in the years since, outlays for health have grown steadily. In 2000–2001, the budget allocation for the health sector was approximately US$144 million; health expenditures per capita were estimated at US$4.50, compared with US$10 on average in sub-Saharan Africa. In 2000 the country counted one hospital bed per 4,900 population and more than 27,000 people per primary health care facility. The physician to population ratio was 1:48,000, the nurse to population ratio, 1:12,000. Overall, there were 20 trained health providers per 100,000 inhabitants. These ratios have since shown some improvement. Health care is disproportionately available in urban centers; in rural areas where the vast majority of the population resides, access to health care varies from limited to nonexistent. As of the end of 2003, the United Nations (UN) reported that 4.4 percent of adults were infected with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS); other estimates of the rate of infection ranged from a low of 7 percent to a high of 18 percent. Whatever the actual rate, the prevalence of HIV/AIDS has contributed to falling life expectancy since the early 1990s. According to the Ministry of Health, one-third of current young adult deaths are AIDS-related. Malnutrition is widespread, especially among children, as is food insecurity. Because of growing population pressure on agricultural and pastoral land, soil degradation, and severe droughts that have occurred each decade since the 1970s, per capita food production is declining. According to the UN and the World Bank, Ethiopia at present suffers from a structural food deficit such that even in the most productive years, at least 5 million Ethiopians require food relief.
In 2002 the government embarked on a poverty reduction program that called for outlays in education, health, sanitation, and water. A polio vaccination campaign for 14 million children has been carried out, and a program to resettle some 2 million subsistence farmers is underway. In November 2004, the government launched a five-year program to expand primary health care. In January 2005, it began distributing antiretroviral drugs, hoping to reach up to 30,000 HIV-infected adults.
=== Ghana ===
In Ghana, most health care is provided by the government, but hospitals and clinics run by religious groups also play an important role. Some for-profit clinics exist, but they provide less than 2% of health services. Health care is very variable through the country. The major urban centres are well served, but rural areas often have no modern health care. Patients in these areas either rely on traditional medicine or travel great distances for care. In 2005, Ghana spent 6.2% of GDP on health care, or US$30 per capita. Of that, approximately 34% was government expenditure.
=== Guinea ===
Guinea has been reorganizing its health system since the Bamako Initiative of 1987 formally promoted community-based methods of increasing accessibility of primary health care to the population, including community ownership and local budgeting, resulting in more efficient and equitable provision of drugs and other essential health care resources.
In June 2011, the Guinean government announced the establishment of an air ticket solidarity levy on all flights taking off from national soil, with funds going to UNITAID to support expanded access to treatment for HIV/AIDS, tuberculosis and malaria. Guinea is among the growing number of countries and development partners using market-based transactions taxes and other innovative financing mechanisms to expand financing options for health care in resource-limited settings.
=== Mali ===
Health in Mali, one of the world's poorest nations, is greatly affected by poverty, malnutrition, and inadequate hygiene and sanitation. Mali's health and development indicators rank among the worst in the world. In 2000 only 62–65 percent of the population was estimated to have access to safe drinking water and only 69 percent to sanitation services of some kind; only 8 percent was estimated to have access to modern sanitation facilities. Only 20 percent of the nation's villages and livestock watering holes had modern water facilities.
Mali is dependent on international development organizations and foreign missionary groups for much of its health care. In 2001 general government expenditures on health constituted 6.8 percent of total general government expenditures and 4.3 percent of gross domestic product (GDP), totaling only about US$4 per capita at an average exchange rate. Medical facilities in Mali are very limited, especially outside of Bamako, and medicines are in short supply. There were only 5 physicians per 100,000 inhabitants in the 1990s and 24 hospital beds per 100,000 in 1998. In 1999 only 36 percent of Malians were estimated to have access to health services within a five-kilometer radius.
=== Morocco ===
According to the United States government, Morocco has inadequate numbers of physicians (0.5 per 1,000 people) and hospital beds (1.0 per 1,000 people) and poor access to water (82 percent of the population) and sanitation (75 percent of the population). The health care system includes 122 hospitals, 2,400 health centers, and 4 university clinics, but they are poorly maintained and lack adequate capacity to meet the demand for medical care. Only 24,000 beds are available for 6 million patients seeking care each year, including 3 million emergency cases. The health budget corresponds to 1.1 percent of gross domestic product and 5.5 percent of the central government budget.
=== Niger ===
Health care system of Niger has a chronic lack of resources and a small number of health providers relative to population. Some medicines are in short supply or unavailable. There are government hospitals in Niamey (with three main hospitals in Niamey, including the Hôpital National de Niamey and the Hôpital National De Lamordé), Maradi, Tahoua, Zinder and other large cities, with smaller medical clinics in most towns. Medical facilities are limited in both supplies and staff, with a small government health care system supplemented by private, charitable, religious, and Non-government organisation operated clinics and public health programs (such as Galmi Hospital near Birnin Konni and Maradi). Government hospitals, as well as public health programmes, fall under the control of the Nigerien Ministry of Health. A number of private for profit clinics ("Cabinets Médical Privé") operate in Niamey. The total expenditure on health per capita in 2005 was Intl $25. There were 377 Physicians in Niger in 2004, a ratio of 0.03 per 10,000 population. In 2003, 89.2 percent of individual expenditures on health care were "out-of-pocket" (paid by the patient).
=== Nigeria ===
Health care provision in Nigeria is a concurrent responsibility of the three tiers of government in the country. However, because Nigeria operates a mixed economy, private providers of health care have a visible role to play in health care delivery. The federal government's role is mostly limited to coordinating the affairs of the university teaching hospitals, while the state government manages the various general hospitals and the local government focus on dispensaries. The total expenditure on health care as % of GDP is 4.6, while the percentage of federal government expenditure on health care is about 1.5%. A long run indicator of the ability of the country to provide food sustenance and avoid malnutrition is the rate of growth of per capita food production; from 1970 to 1990, the rate for Nigeria was 0.25%. Though small, the positive rate of per capita may be due to Nigeria's importation of food products. Historically, health insurance in Nigeria can be applied to a few instances: government-paid health care provided and financed for all citizens, health care provided by government through a special health insurance scheme for government employees and private firms entering contracts with private health care providers. However, there are few people who fall within the three instances. In May 1999, the government created the National Health Insurance Scheme, the scheme encompasses government employees, the organized private sector and the informal sector. Legislative wise, the scheme also covers children under five, permanently disabled persons and prison inmates. In 2004, the administration of Obasanjo further gave more legislative powers to the scheme with positive amendments to the original 1999 legislative act.
=== Senegal ===
The health budget in Senegal has tripled between 1980 and 2000, leading to the Senegalese people leading healthier and longer lives – the life expectancy at birth is approximately 55.34 years for men, 58.09 years for women, and 56.69 years for the entire population. Also, the prevalence rate of AIDS in Senegal is one of the lowest in Africa, at 0.9%. However, large disparities still exist in Senegal's health coverage, with 70% of doctors, and 80% of pharmacists and dentists, living in the nation's capital city, Dakar.
=== South Africa ===
In South Africa, parallel private and public systems exist. The public system serves the vast majority of the population, but is chronically underfunded and understaffed. The wealthiest 20% of the population uses the private system and are far better served. This division in substantial ways perpetuates racial inequalities created in the pre-apartheid segregation era and apartheid era of the 20th century. In 2005, South Africa spent 8.7% of GDP on health care, or US$437 per capita. Of that, approximately 42% was government expenditure.
=== Sudan ===
Outside urban areas, little health care is available in Sudan, helping account for a relatively low average life expectancy of 57 years and an infant mortality rate of 69 deaths per 1,000 live births, low by standards in Middle Eastern but not African countries. For most of the period since independence in 1956, Sudan has experienced civil war, which has diverted resources to military use that otherwise might have gone into health care and training of professionals, many of whom have migrated in search of more gainful employment. In 1996 the World Health Organization estimated that there were only 9 doctors per 100,000 people, most of them in regions other than the South. Substantial percentages of the population lack access to safe water and sanitary facilities. Malnutrition is widespread outside the central Nile corridor because of population displacement from war and from recurrent droughts; these same factors together with a scarcity of medicines make diseases difficult to control. Child immunization against most major childhood diseases, however, had risen to approximately 60 percent by the late 1990s from very low rates in earlier decades. Spending on health care is quite low – only 1 percent of gross domestic product (GDP) in 1998 (latest data). The United Nations placed the rate of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) infection in late 2003 at 2.3 percent for adults, quite low by regional standards. The United Nations suggested, however, that the rate could be as high as 7.2 percent. Between 400,000 and 1.3 million adults and children were living with HIV, and AIDS deaths numbered 23,000. As of late 2004, some 4 million persons in the South had been internally displaced and more than 2 million had died or been killed as a result of two decades of war. Comparable figures for Darfur were 1.6 million displaced and 70,000 dead since fighting began there in early 2003.
=== Zimbabwe ===
Zimbabwe now has one of the lowest life expectancies on Earth – 44 for men and 43 for women, down from 60 in 1990. The rapid drop has been ascribed mainly to the HIV/AIDS pandemic. Infant mortality has risen from 59 per thousand in the late 1990s to 123 per 1000 by 2004. The health system has more or less collapsed: By the end of November 2008, three of Zimbabwe's four major hospitals had shut down, along with the Zimbabwe Medical School and the fourth major hospital had two wards and no operating theatres working. Due to hyperinflation, those hospitals still open are not able to obtain basic drugs and medicines. The ongoing political and economic crisis also contributed to the emigration of the doctors and people with medical knowledge. In August 2008, large areas of Zimbabwe were struck by the ongoing cholera epidemic.
== Americas ==
=== Argentina ===
Argentina's health care system is composed of three sectors: the public sector, financed through taxes; the private sector, financed through voluntary insurance schemes; and the social security sector, financed through obligatory insurance schemes. The Ministry of Health and Social Action (MSAS), oversees all three subsectors of the health care system and is responsible for setting of regulation, evaluation and collecting statistics.
Argentina has three sectors. The public sector is funded and managed by Obras Sociales, umbrella organizations for Argentine worker's unions. There are over 300 Obras Sociales in Argentina, each chapter being organized according to the occupation of the beneficiary. These organizations vary greatly in quality and effectiveness. The top 30 chapters hold 73% of the beneficiaries and 75% of resources for all Obras Sociales schemes and the monthly average a beneficiary receives varies from $5–80 per month. MSAS has established a Solidarity Redistribution Fund (FSR) to try to address these beneficiary inequities. Only workers employed in the formal sector are covered under Obras Sociales insurance schemes and after Argentina's economic crisis of 2001, the number of those covered under these schemes fell slightly (as unemployment increased and employment in the informal sector rose). In 1999, there were 8.9 million beneficiaries covered by Obras Sociales. The private health care sector in Argentina is characterized by great heterogeneity and is made up of a great number of fragmented facilities and small networks; it consists of over 200 organizations and covers approximately 2 million Argentines.
Private insurance often overlaps with other forms of health care coverage, thus it is difficult to estimate the degree to which beneficiaries are dependent on the public and private sectors. According to a 2000 report by the IRBC, foreign competition has increased in Argentina's private sector, with Swiss, American and other Latin American health care providers entering the market in recent years. This has been accompanied by little formal regulation. The public system serves those not covered by Obras Sociales or private insurance schemes. It also provides emergency services. According to above-mentioned IRBC report, Argentina's public system exhibits serious structural deterioration and managerial inefficiency; a high degree of administrative centralization at the provincial level; rigidity in its staffing structure and labour relationships; no adequate system of incentives; inadequate information systems on which to base decision-making and control; serious deficits in facilities and equipment maintenance; and a system of management ill-suited to its size. The public system is highly decentralized to the provincial level; often primary care is even under the purview of local townships. Since 2001, the number of Argentines relying on public services has seen an increase. According to 2000 figures, 37.4% of Argentines had no health insurance, 48.8 were covered under Obras Sociales, 8.6% had private insurance, and 3.8% were covered by both Obras Sociales and private insurance schemes.
=== Brazil ===
The Brazilian health system is composed of a large, public, government managed system, the SUS (Sistema Único de Saúde), which serves the majority of the population completely free of charge or any form of fee, and a private sector, managed by health insurance funds and private entrepreneurs.
The public health system, SUS, was established in 1988 by the Brazilian Constitution, and sits on 3 basic principles of universality, comprehensiveness and equity. Universality states that all citizens must have access to health care services, without any form of discrimination, regarding skin color, income, social status, gender or any other variable. There is no form of charging or payment in any public hospitals or clinics, either for Brazilian nationals or foreigners.
Government standards state that citizen's health is the result of multiple variables, including employment, income, access to land, sanitation services, access and quality of health services, education, psychic, social and family conditions, and are entitled to full and complete health care, comprising prevention, treatment and rehabilitation. Equity states that health policies should be oriented towards the reduction of inequalities between population groups and individuals, being the most needed the ones for whom policies should be first directed.
SUS also has guidelines for its implementation, the most peculiar being popular participation, which defines that all policies are to be planned and supervised directly by the population, through local, city, state and national health councils and conferences.
The level of public spending is particularly high in relation to GDP for a country of Brazil's income level and in comparison with its emerging-market peers. Government outlays on health care alone account for nearly 9% of GDP, the second largest item of spending following social protection. In health care, a number of conventional output indicators are not out of step with OECD averages. Following the decentralization of service delivery in the early 1990s, increasing emphasis has appropriately been placed on enhancing preventive care. But, in a decentralized setting, cost-effectiveness depends a great deal on the ability of service deliverers to exploit economies of scale and scope. Experience with inter-municipal initiatives for procurement, as well as flexible arrangements for hospital administration and human-resource management, is by and large positive.
Private Health Insurance is widely available in Brazil and may be purchased on an individual-basis or obtained as a work benefit (major employers usually offer private health insurance benefits). Public health care is still accessible for those who choose to obtain private health insurance. As of March 2007, more than 37 million Brazilians had some sort of private health insurance.
=== Canada ===
=== Chile ===
Chile has maintained a dual health care system in which its citizens can voluntarily opt for coverage by either the public National Health Insurance Fund or any of the country's private health insurance companies. 68% of the population is covered by the public fund and 18% by private companies. The remaining 14% is covered by other not-for-profit agencies or has no specific coverage. The system's duality has led to increasing inequalities prompting the Chilean government to introduce major reforms in health care provision. Chile's health care system is funded by a universal income tax deduction equal to 7% of every worker's wage. Many private health insurance companies encourage people to pay a variable extra on top of the 7% premium to upgrade their basic health plans. Because of this arrangement, the public and private health subsystems have existed almost completely separate from each other rather than coordinating to achieve common health objectives.
=== Colombia ===
=== Costa Rica ===
Costa Rica provides universal health care to its citizens and permanent residents.
=== Cuba ===
Health care in Cuba consists of a government-coordinated system that guarantees universal coverage and consumes a lower proportion of the nation's GDP (7.3%) than some highly privatised systems (e.g. USA: 16%) (OECD 2008). The system does charge fees in treating elective treatment for patients from abroad, but tourists who fall ill are treated free in Cuban hospitals. Cuba attracts patients mostly from Latin America and Europe by offering care of comparable quality to a developed nation but at much lower prices. Cuba's own health indicators are the best in Latin America and surpass those of the US in some respects (infant mortality rates, underweight babies, HIV infection, immunisation rates, doctor per population rates). (UNDP 2006: Tables 6,7,9,10) In 2005, Cuba spent 7.6% of GDP on health care, or US$310 per capita. Of that, approximately 91% was government expenditure.
=== El Salvador ===
Healthcare in El Salvador is free at the point of delivery. The public health system, which is regulated by the Ministry of Health and Social Welfare, has 30 public hospitals in the country plus various primary care facilities and 27 basic health care systems. According to the law of El Salvador, all individuals are given basic health services in public health institutions.
=== Mexico ===
Health care in Mexico is provided via public institutions or private entities. Health care delivered through private health care organizations operates entirely on the free-market system (e.g. it is available to those who can afford it). Public health care delivery, on the other hand, is accomplished via an elaborate provisioning and delivery system put in place by the Mexican Federal Government and the Mexican Social Security Institute (IMSS).
Advances in medicine and increasing health knowledge have increased the life expectancy in Mexico by an average of 25 years in the last years of the 20th century. Of the 6.6% GDP of government revenue spent on health, this provides only health insurance to 40% of the population who are privately employed. The health care system has three components: the social security institute, governmental services for the un-insured (Seguro Popular), and the private sector that is financed almost completely from out of pocket money. The IMSS, the largest social institution in Latin America, is the governmental institution responsible of executing the Federal Government's health policy. The number of public hospitals in Mexico has increased 41% in ten years from 1985 to 1995.
According to the site www.internationalliving.com, health care in Mexico is described as very good to excellent while being highly affordable, with every medium to large city in Mexico having at least one first-rate hospital. In fact, some California insurers sell health insurance policies that require members to go to Mexico for health care where costs are 40% lower. Some of Mexico's top-rate hospitals are internationally accredited. Americans, particularly those living near the Mexican border, now routinely cross the border into Mexico for medical care. Popular specialties include dentistry and plastic surgery. Mexican dentists often charge 20 to 25 percent of US prices, while other procedures typically cost a third what they would cost in the US.
=== Paraguay ===
In terms of major indicators, health in Paraguay ranks near the median among South American countries. In 2003 Paraguay had a child mortality rate of 1.5 deaths per 1,000 children, ranking it behind Argentina, Colombia, and Uruguay but ahead of Brazil and Bolivia. The health of Paraguayans living outside urban areas is generally worse than those residing in cities. Many preventable diseases, such as Chagas' disease, run rampant in rural regions. Parasitic and respiratory diseases, which could be controlled with proper medical treatment, drag down Paraguay's overall health. In general, malnutrition, lack of proper health care, and poor sanitation are the root of many health problems in Paraguay.
Health care funding from the national government increased gradually throughout the 1980s and 1990s. Spending on health care rose to 1.7 percent of the gross domestic product (GDP) in 2000, nearly triple the 0.6 percent of GDP spent in 1989. But during the past decade, improvement in health care has slowed. Paraguay spends less per capita (US$13–20 per year) than most other Latin American countries. A 2001 survey indicated that 27 percent of the population still had no access to medical care, public or private. Private health insurance is very limited, with pre-paid plans making up only 11 percent of private expenditures on health care. Thus, most of the money spent on private health care (about 88 percent) is on a fee-for-service basis, effectively preventing the poor population from seeing private doctors. According to recent estimates, Paraguay has about 117 physicians and 20 nurses per 100,000 population.
=== Peru ===
Peruvian citizens can opt between a state-owned healthcare system and various private insurance companies. The country has a life expectancy higher than the global average but it also has a high risk of infection, especially near the jungle and other isolated areas, due to the warm climate that favours the reproduction of various insects and bacteria. The mortality rate of the population has been decreasing steadily since 1990 and now stands at 19 deaths per 1000 live births.
=== Trinidad and Tobago ===
Trinidad and Tobago operates under a two-tier health care system. That is, there is the existence of both private health care facilities and public health care facilities.
The Ministry of Health is responsible for leading the health sector. The service provision aspect of public health care has been devolved to newly created entities, the Regional Health Authorities (RHAs). The Ministry of Health is shifting its focus to concentrate on policy development, planning, monitoring and evaluation, regulation, financing and research. Citizens can access government-paid health care at public health care facilities where health insurance is not required. The health care system in the country is universal as almost all citizens utilise the services provided. Some, though, opt for private health care facilities for their ailments.
Recently, the Government of Trinidad and Tobago has launched CDAP (Chronic Disease Assistance Programme). The Chronic Disease Assistance Programme provides citizens with government-paid prescription drugs and other pharmaceutical items to combat several health conditions.
=== United States ===
The United States currently operates under a mixed market health care system. Government sources (federal, state, and local) account for 45% of U.S. health care expenditures. Private sources account for the remainder of costs, with 38% of people receiving health coverage through their employers and 17% arising from other private payment such as private insurance and out-of-pocket co-pays. Health care reform in the United States usually focuses around three suggested systems, with proposals currently underway to integrate these systems in various ways to provide a number of health care options. First is single-payer, a term meant to describe a single agency managing a single system, as found in many other developed countries as well as some states and municipalities within the United States. Second are employer or individual insurance mandates. Finally, there is consumer-driven health, in which systems, consumers, and patients have more control of how they access care. Over the past thirty years, most of the nation's health care has moved from the second model operating with not-for-profit institutions to the third model operating with for-profit institutions.
In the US, the social and political issues surrounding access to health care have led to vigorous public debate and the almost colloquial use of terms such as health care (medical management of illness), health insurance (reimbursement of health care costs), and public health (the collective state and range of health in a population). As of 2023, 8% of US citizens do not have health insurance. State boards and the Department of Health regulate inpatient care to reduce the national health care deficit. To tackle the problems of the increasing number of uninsured, and costs associated with the US health care system, President Barack Obama says he favors the creation of a universal health care system. However, this view is not shared across the country (see, for example, quotes from New York Times opinion columnist Paul Krugman and Factcheck.org).
A few states have taken serious steps toward universal health care coverage, most notably Minnesota, Massachusetts and Connecticut, with recent examples being the Massachusetts 2006 Health Reform Statute and Connecticut's SustiNet plan to provide quality, affordable health care to state residents.
The state of Oregon and the city of San Francisco are both examples of governments that adopted universal healthcare systems for strictly fiscal reasons.
The United States is alone among developed nations in not having a universal health care system; the 2010 Patient Protection and Affordable Care Act provides a nationwide health insurance exchange that came to fruition in 2014, but this is not universal in the way similar countries mean it. However, the ACA made several meaningful changes, including barring coverage denial due to pre-existing conditions, creating Medicaid expansion, and creating subsidized insurance exchanges. Healthcare in the U.S. has significant publicly funded components. Medicare covers the elderly and disabled with a historical work record, Medicaid is available to most, but not all, of the poor, and the State Children's Health Insurance Program covers children of low-income families. The Veterans Health Administration directly provides health care to U.S. military veterans through a nationwide network of government hospitals; while active duty service members, retired service members and their dependents are eligible for benefits through TRICARE. Together, these tax-financed programs cover 36.8% of the population and make the government the largest health insurer in the nation. As of 2013, public sources accounted for 64.3% of healthcare spending in the U.S. The U.S. also spends 17.6% of GDP per year on healthcare, ahead of the next highest spender, Germany, at 12.6%.
=== Venezuela ===
The right to health care is guaranteed in the Venezuelan Constitution. Government campaigns for the prevention, elimination, and control of major health hazards have been generally successful. Immunization campaigns have systematically improved children's health, and regular campaigns to destroy disease-bearing insects and to improve water and sanitary facilities have all boosted Venezuela's health indicators to some of the highest levels in Latin America. The availability of low- or no-cost health care provided by the Venezuelan Institute of Social Security has also made Venezuela's health care infrastructure one of the more advanced in the region. However, despite being the most comprehensive and well funded in the region, the health care system has deteriorated sharply since the 1980s. Government expenditures on health care constituted an estimated 4.1 percent of gross domestic product in 2002. Total health expenditures per capita in 2001 totaled US$386. Per capita government expenditures on health in 2001 totaled US$240.
In April 2017 Venezuela's health ministry reported that maternal mortality jumped by 65% in 2016 and that the number of infant deaths rose by 30%. It also said that the number of cases of malaria was up by 76%. The ministry had not reported health data in two years. Venezuela is suffering from acute shortages of food and medicines.
== Asia ==
=== Afghanistan ===
The citizens of Afghanistan benefited from a well established free universal healthcare system until the arrival of the Mujahideen in 1992; which destroyed the health system of Afghanistan, forcing most medical professionals to leave the country and causing all medical training programs to cease. In 2004 Afghanistan had one medical facility for every 27,000 people, and some centers were responsible for as many as 300,000 people. In 2004 international organizations provided a large share of medical care. An estimated one-quarter of the population had no access to health care. In 2003 there were 11 physicians and 18 nurses per 100,000 population, and the per capita health expenditure was US$28.
=== Bhutan ===
Bhutan's health care system development accelerated in the early 1960s with the establishment of the Department of Public Health and the opening of new hospitals and dispensaries throughout the country. By the early 1990s, health care was provided through twenty-nine general hospitals (including five leprosy hospitals, three army hospitals, and one mobile hospital), forty-six dispensaries, sixty-seven basic health units, four indigenous-medicine dispensaries, and fifteen malaria eradication centers. The major hospitals were the National Referral Hospital in Thimphu, and other hospitals in Geylegphug, and Trashigang. Hospital beds in 1988 totaled 932. There was a severe shortage of health care personnel with official statistics reporting only 142 physicians and 678 paramedics, about one health care professional for every 2,000 people, or only one physician for almost 10,000 people. Training for health care assistants, nurses' aides, midwives, and primary health care workers was provided at the Royal Institute of Health Sciences, associated with Thimphu General Hospital, which was established in 1974. Graduates of the school were the core of the national public health system and helped staff the primary care basic health units throughout the country. Additional health care workers were recruited from among volunteers in villages to supplement primary health care. The Institute of Traditional Medicine Services supports indigenous medical centers associated with the district hospitals.
=== China ===
The effective public health work in controlling epidemic disease during the early years of China and, after reform began in 1978, the dramatic improvements in nutrition greatly improved the health and life expectancy of the Chinese people. The 2000 WHO World Health Report – Health systems: improving performance found that China's health care system before 1980 performed far better than countries at a comparable level of development, since 1980 ranks much lower than comparable countries. The famed "barefoot doctor" system was abolished in 1981.
China is undertaking a reform on its health care system. The New Rural Co-operative Medical Care System (NRCMCS) is a new 2005 initiative to overhaul the health care system, particularly intended to make it more affordable for the rural poor. Under the NRCMCS, the annual cost of medical cover is 50 yuan (US$7) per person. Of that, 20 yuan is paid in by the central government, 20 yuan by the provincial government and a contribution of 10 yuan is made by the patient. As of September 2007, around 80% of the whole rural population of China had signed up (about 685 million people). The system is tiered, depending on the location. If patients go to a small hospital or clinic in their local town, the scheme will cover from 70 to 80% of their bill. If they go to a county one, the percentage of the cost being covered falls to about 60%. And if they need specialist help in a large modern city hospital, they have to bear most of the cost themselves, the scheme would cover about 30% of the bill.
Health care was provided in both rural and urban areas through a three-tiered system. In rural areas the first tier was made up of barefoot doctors working out of village medical centers. They provided preventive and primary-care services, with an average of two doctors per 1,000 people. At the next level were the township health centers, which functioned primarily as out-patient clinics for about 10,000 to 30,000 people each. These centers had about ten to thirty beds each, and the most qualified members of the staff were assistant doctors. The two lower-level tiers made up the "rural collective health system" that provided most of the country's medical care. Only the most seriously ill patients were referred to the third and final tier, the county hospitals, which served 200,000 to 600,000 people each and were staffed by senior doctors who held degrees from 5-year medical schools. Health care in urban areas was provided by paramedical personnel assigned to factories and neighborhood health stations. If more professional care was necessary the patient was sent to a district hospital, and the most serious cases were handled by municipal hospitals. To ensure a higher level of care, a number of state enterprises and government agencies sent their employees directly to district or municipal hospitals, circumventing the paramedical, or barefoot doctor, stage.
=== India ===
In India, the hospitals and clinics are run by government, charitable trusts and by private organizations. The public clinics in rural areas are called Primary Health Centres (PHCs). Public hospitals are free for all and entirely funded through taxes. Major hospitals are located in district headquarters or major cities. At the federal level, a national health insurance program was launched in 2018 by the Government of India, called Ayushman Bharat. This aimed to cover the bottom 50% (500 million people) of the country's population working in the unorganized sector (enterprises having less than 10 employees) and offers them free treatment even at private hospitals. For people working in the organized sector (enterprises with more than 10 employees) and earning a monthly salary of up to Rs 21000 are covered by the social insurance scheme of Employees' State Insurance which entirely funds their healthcare (along with pension and unemployment benefits), both in public and private hospitals. People earning more than that amount are provided health insurance coverage by their employers through the many public or private insurance companies. As of 2020, 300 million Indians are covered by insurance bought from one of the public or private insurance companies by their employers as group or individual plans. Unemployed people without coverage are covered by the various state insurance schemes if they do not have the means to pay for it.
In 2019, the total net government spending on healthcare was $36 billion or 1.23% of its GDP. Patients generally prefer private health clinics. These days some of the major corporate hospitals are attracting patients from neighboring countries such as Pakistan, countries in the Middle East and some European countries by providing quality treatment at low cost. In 2005, India spent 5% of GDP on health care, or US$36 per capita. Of that, approximately 19% was government expenditure.
=== Indonesia ===
Indonesia's community health system were organized in three tier, on top of the chart is Community Health Center (Puskesmas), followed by Health Sub-Center on the second level and Village-Level Integrated Post at the third level. According to data from the Ministry of Health of Indonesia there are 2454 hospitals around the country, with total of 305,242 bed counting 0.9 bed per 100,000 inhabitant. Among these 882 of these hospitals are government owned and 1509 are private hospitals. According to the Worldbank data in 2012, there are 0.2 physicians per 1,000 people, with 1.2 Nurses and Midwives per 1,000 people in Indonesia. Out of all the 2454 hospitals in Indonesia, 20 have been accredited by Joint Commission international (JCI) as of 2015. In addition there are 9718 government financed Puskesmas (Health Community Center) listed by the Ministry of Health of Indonesia, which provide comprehensive healthcare and vaccination for the population in the sub-district level. Both traditional and modern health practices are employed. A data taken from World Health Organization (WHO) of 2013 shows that government health expenditures are about 3.1 percent of the total gross domestic product (GDP).
=== Israel ===
In Israel, the publicly funded medical system is universal and compulsory. In 2005, Israel spent 7.8% of GDP on health care, or US$1,533 per capita. Of that, approximately 66% was government expenditure.
=== Japan ===
In Japan, services are provided either through regional/national public hospitals or through private hospitals/clinics, and patients have universal access to any facility, though hospitals tend to charge higher for those without a referral. Public health insurance covers most citizens/residents and pays 70% or more cost for each care and each prescribed drug. Patients are responsible for the remainder (upper limits apply). The monthly insurance premium is 0–50,000 JPY per household (scaled to annual income). Supplementary private health insurance is available only to cover the co-payments or non-covered costs, and usually makes a fixed payment per days in hospital or per surgery performed, rather than per actual expenditure. In 2005, Japan spent 8.2% of GDP on health care, or US$2,908 per capita. Of that, approximately 83% was government expenditure.
=== Jordan ===
In comparison to most of its neighbors, Jordan has quite an advanced health care system, although services remain highly concentrated in Amman. Government figures have put total health spending in 2002 at some 7.5 percent of Gross domestic product (GDP), while international health organizations place the figure even higher, at approximately 9.3 percent of GDP. The country's health care system is divided between public and private institutions. In the public sector, the Ministry of Health operates 1,245 primary health care centers and 27 hospitals, accounting for 37 percent of all hospital beds in the country; the military's Royal Medical Services runs 11 hospitals, providing 24 percent of all beds; and the Jordan University Hospital accounts for 3 percent of total beds in the country. The private sector provides 36 percent of all hospital beds, distributed among 56 hospitals. On 1 June 2007, Jordan Hospital (as the biggest private hospital) was the first general specialty hospital who gets the international accreditation (JCI). Treatment cost in Jordan hospitals is less than in other countries.
=== Kazakhstan ===
In principle, health care is paid for by the government. However, bribes often are necessary to obtain needed care. The quality of health care, which remained entirely under state control in 2006, has declined in the post-Soviet era because of insufficient funding and the loss of technical experts through emigration. Between 1989 and 2001, the ratio of doctors per 10,000 inhabitants fell by 15 percent, to 34.6, and the ratio of hospital beds per 10,000 inhabitants fell by 46 percent, to 74. By 2005 those indicators had recovered somewhat, to 55 and 77, respectively. Since 1991, health care has consistently lacked adequate government funding; in 2005 only 2.5 percent of gross domestic product went for that purpose. A government health reform program aims to increase that figure to 4 percent in 2010. A compulsory health insurance system has been in the planning stages for several years. Wages for health workers are extremely low, and equipment is in critically short supply. The main foreign source of medical equipment is Japan. Because of cost, the emphasis of treatment increasingly is on outpatient care instead of the hospital care preferred under the Soviet system. The health system is in crisis in rural areas such as the Aral Sea region, where health is most affected by pollution.
=== Malaysia ===
Health care in Malaysia is divided into private and public sectors. Doctors are required to undergo a 2-year internship and perform 3 years of service with public hospitals throughout the nation, ensuring adequate coverage of medical needs for the general population. Foreign doctors are encouraged to apply for employment in Malaysia, especially if they are qualified to a higher level.
Malaysian society places importance on the expansion and development of health care, putting 5% of the government social sector development budget into public health care – an increase of more than 47% over the previous figure. This has meant an overall increase of more than RM 2 billion. With a rising and ageing population, the Government wishes to improve in many areas including the refurbishment of existing hospitals, building and equipping new hospitals, expansion of the number of polyclinics, and improvements in training and expansion of telehealth. Over the last couple of years they have increased their efforts to overhaul the systems and attract more foreign investment.
There is still a shortage in the medical workforce, especially of highly trained specialists. As a result, certain medical care and treatment is available only in large cities. Recent efforts to bring many facilities to other towns have been hampered by lack of expertise to run the available equipment made ready by investments.
The majority of private hospital facilities are in urban areas and, unlike many of the public hospitals, are equipped with the latest diagnostic and imaging facilities.
=== North Korea ===
North Korea has a national medical service and health insurance system. As of 2000, some 99 percent of the population had access to sanitation, and 100 percent had access to water, but water was not always potable. Medical treatment is paid for by the state. In the past, there reportedly has been one doctor for every 700 inhabitants and one hospital bed for every 350 inhabitants. Health expenditures in 2001 were 2.5 percent of gross domestic product, and 73 percent of health expenditures were made in the public sector. There were no reported human immuno-deficiency virus/acquired immune deficiency syndrome (HIV/AIDS) cases as of 2007. However, it is estimated that between 500,000 and 3 million people died from famine in the 1990s, and a 1998 United Nations (UN) World Food Program report revealed that 60 percent of children suffered from malnutrition, and 16 percent were acutely malnourished. UN statistics for the period 1999–2001 reveal that North Korea's daily per capita food supply was one of the lowest in Asia, exceeding only that of Cambodia, Laos, and Tajikistan, and one of the lowest worldwide. Because of continuing economic problems, food shortages and chronic malnutrition prevail in the 2000s.
=== Oman ===
Oman's healthcare system was ranked at number 8 by the WHO health systems ranking in 2000. Universal healthcare (including prescriptions and dental care) is provided automatically to all citizens and also to expatriates working in the public sector by the Ministry of Health. Non-eligible individuals such as expatriates working in the private sector and foreign visitors can be treated in the government hospitals and clinics for a reasonable fee or they can opt for the more expensive private clinics and medical centres. The Ministry of Health also finances the treatment of citizens abroad if the required treatment is not available in Oman. The life expectancy in Oman as of 2007 was 71.6. It had 1.81 doctors per 1000 pop., 1.9 beds per 1000 pop. and an infant mortality rate of 9 per 1000 live births. Health expenditure accounts for 4.5% of government revenue.
=== Pakistan ===
Pakistan's health indicators, health funding, and health and sanitation infrastructure are generally poor, particularly in rural areas. About 19 percent of the population is malnourished – a higher rate than the 17 percent average for developing countries – and 30 percent of children under age five are malnourished. Leading causes of sickness and death include gastroenteritis, respiratory infections, congenital abnormalities, tuberculosis, malaria, and typhoid fever. The United Nations estimates that in 2003 Pakistan's human immunodeficiency virus (HIV) prevalence rate was 0.1 percent among those 15–49, with an estimated 4,900 deaths from acquired immune deficiency syndrome (AIDS). AIDS is a major health concern, and both the government and religious community are engaging in efforts to reduce its spread. In 2003 there were 68 physicians for every 100,000 persons in Pakistan. According to 2002 government statistics, there were 12,501 health institutions nationwide, including 4,590 dispensaries, 906 hospitals with a total of 80,665 hospital beds, and 550 rural health centers with a total of 8,840 beds. According to the World Health Organization, Pakistan's total health expenditures amounted to 3.9 percent of gross domestic product (GDP) in 2001, and per capita health expenditures were US$16. The government provided 24.4 percent of total health expenditures, with the remainder being entirely private, out-of-pocket expenses.
=== Philippines ===
Since 1995, PhilHealth has aimed for universal healthcare coverage through a governmental health insurance scheme. In 2000 the Philippines had about 95,000 physicians, or about 1 per 800 people. In 2001 there were about 1,700 hospitals, of which about 40 percent were government-run and 60 percent private, with a total of about 85,000 beds, or about one bed per 900 people. The leading causes of morbidity as of 2002 were diarrhea, bronchitis, pneumonia, influenza, hypertension, tuberculosis, heart disease, malaria, chickenpox, and measles. Cardiovascular diseases account for more than 25 percent of all deaths. According to official estimates, 1,965 cases of human immunodeficiency virus (HIV) were reported in 2003, of which 636 had developed acquired immune deficiency syndrome (AIDS). Other estimates state that there may have been as many as 9,400 people living with HIV/AIDS in 2001.
=== Singapore ===
Health care in Singapore is mainly under the responsibility of the Singapore Government's Ministry of Health. Singapore generally has an efficient and widespread system of health care. It implements a universal health care system, and co-exists with private health care system. Infant mortality rate: in 2006 the crude birth rate stood at 10.1 per 1000, and the crude death rate was also one of the lowest in the world at 4.3 per 1000. In 2006, the total fertility rate was only 1.26 children per woman, the 3rd lowest in the world and well below the 2.10 needed to replace the population. Singapore was ranked 6th in the World Health Organization's ranking of the world's health systems in the year 2000.
Singapore has a universal health care system where government ensures affordability, largely through compulsory savings and price controls, while the private sector provides most care. Overall spending on health care amounts to only 3% of annual GDP. Of that, 66% comes from private sources. Singapore currently has the lowest infant mortality rate in the world (equaled only by Iceland) and among the highest life expectancies from birth, according to the World Health Organization. Singapore has "one of the most successful health care systems in the world, in terms of both efficiency in financing and the results achieved in community health outcomes," according to an analysis by global consulting firm Watson Wyatt. Singapore's system uses a combination of compulsory savings from payroll deductions (funded by both employers and workers) a nationalized catastrophic health insurance plan, and government subsidies, as well as "actively regulating the supply and prices of health care services in the country" to keep costs in check; the specific features have been described as potentially a "very difficult system to replicate in many other countries." Many Singaporeans also have supplemental private health insurance (often provided by employers) for services not covered by the government's programs.
Singapore's well-established health care system comprises a total of 13 private hospitals, 10 public (government) hospitals and several specialist clinics, each specializing in and catering to different patient needs, at varying costs.
Patients are free to choose the providers within the government or private health care delivery system and can walk in for a consultation at any private clinic or any government polyclinic. For emergency services, patients can go at any time to the 24-hour Accident & Emergency Departments located in the government hospitals.
Singapore's medical facilities are among the finest in the world, with well qualified doctors and dentists, many trained overseas.
Singapore has medical savings account system known as Medisave.
=== South Korea ===
Healthcare in South Korea is universal, although a significant portion of healthcare is privately funded. South Korea's healthcare system is based on the National Health Insurance Service, a public health insurance program run by the Ministry of Health and Welfare to which South Koreans of sufficient income must pay contributions to in order to insure themselves and their dependants, and the Medical Aid Program, a social welfare program run by the central government and local governments to insure those unable to pay National Health Insurance contributions. In 2015, South Korea ranked first in the OECD for healthcare access. Satisfaction of healthcare has been consistently among the highest in the world – South Korea was rated as the second most efficient healthcare system by Bloomberg.
=== Syria ===
The Syrian Ba'ath Party has placed an emphasis on health care, but funding levels have not been able to keep up with demand or maintain quality. Health expenditures reportedly accounted for 2.5 percent of the gross domestic product (GDP) in 2001. Syria's health system is relatively decentralized and focuses on offering primary health care at three levels: village, district, and provincial. According to the World Health Organization (WHO), in 1990 Syria had 41 general hospitals (33 public, 8 private), 152 specialized hospitals (16 public, 136 private), 391 rural health centers, 151 urban health centers, 79 rural health units, and 49 specialized health centers; hospital beds totaled 13,164 (77 percent public, 23 percent private), or 11 beds per 10,000 inhabitants. The number of state hospital beds reportedly fell between 1995 and 2001, while the population had an 18 percent increase, but the opening of new hospitals in 2002 caused the number of hospital beds to double. WHO reported that in 1989 Syria had a total of 10,114 physicians, 3,362 dentists, and 14,816 nurses and midwives; in 1995 the rate of health professionals per 10,000 inhabitants was 10.9 physicians, 5.6 dentists, and 21.2 nurses and midwives. Despite overall improvements, Syria's health system exhibits significant regional disparities in the availability of health care, especially between urban and rural areas. The number of private hospitals and doctors increased by 41 percent between 1995 and 2001 as a result of growing demand and growing wealth in a small sector of society. Almost all private health facilities are located in large urban areas such as Damascus, Aleppo, Tartus, and Latakia.
=== Taiwan ===
The current health care system in Taiwan, known as National Health Insurance (NHI), was instituted in 1995. NHI is a single-payer compulsory social insurance plan which centralizes the disbursement of health care dollars. The system promises equal access to health care for all citizens, and the population coverage had reached 99% by the end of 2004. NHI is mainly financed through premiums, which are based on the payroll tax, and is supplemented with out-of-pocket payments and direct government funding. In the initial stage, fee-for-service predominated for both public and private providers. Most health providers operate in the private sector and form a competitive market on the health delivery side. However, many health care providers took advantage of the system by offering unnecessary services to a larger number of patients and then billing the government. In the face of increasing loss and the need for cost containment, NHI changed the payment system from fee-for-service to a global budget, a kind of prospective payment system, in 2002.
According to T.R. Reid, Taiwan achieves "remarkable efficiency", costing ≈6 percent of GDP universal coverage; however, this underestimates the cost as it is not fully funded and the government is forced to borrow to make up the difference. "And frankly, the solution is fairly obvious: increase the spending a little, to maybe 8 percent of GDP. Of course, if Taiwan did that, it would still be spending less than half of what America spends."
=== Thailand ===
The majority of health care services in Thailand is delivered by the public sector, which includes 1,002 hospitals and 9,765 health stations. Universal health care is provided through three programs: the civil service welfare system for civil servants and their families, Social Security for private employees, and the Universal Coverage scheme theoretically available to all other Thai nationals. Some private hospitals are participants in these programs, though most are financed by patient self-payment and private insurance.
The Ministry of Public Health (MOPH) oversees national health policy and also operates most government health facilities. The National Health Security Office (NHSO) allocates funding through the Universal Coverage program. Other health-related government agencies include the Health System Research Institute (HSRI), Thai Health Promotion
Foundation ("ThaiHealth"), National Health Commission Office (NHCO), and the Emergency Medical Institute of Thailand (EMIT). Although there have been national policies for decentralization, there has been resistance in implementing such changes and the MOPH still directly controls most aspects of health care.
=== Turkmenistan ===
In the post-Soviet era, reduced funding has put the health system in poor condition. In 2002 Turkmenistan had 50 hospital beds per 10,000 population, less than half the number in 1996. Overall policy has targeted specialized inpatient facilities to the detriment of basic, outpatient care. Since the late 1990s, many rural facilities have closed, making care available principally in urban areas. President Niyazov's 2005 proposal to close all hospitals outside Ashgabat intensified this trend. Physicians are poorly trained, modern medical techniques are rarely used, and medications are in short supply. In 2004 Niyazov dismissed 15,000 medical professionals, exacerbating the shortage of personnel. In some cases, professionals have been replaced by military conscripts. Private health care is rare, as the state maintains a near monopoly and most people are too poor to afford it. Government-paid public health care that it inherited from the Soviet Union was abolished in 2004.
=== United Arab Emirates ===
Standards of health care are considered to be generally high in the United Arab Emirates, resulting from increased government spending during strong economic years. According to the UAE government, total expenditures on health care from 1996 to 2003 were US$436 million. According to the World Health Organization, in 2004 total expenditures on health care constituted 2.9 percent of gross domestic product (GDP), and the per capita expenditure for health care was US$497. Health care currently is government-paid only for UAE citizens. Effective January 2006, all residents of Abu Dhabi are covered by a new comprehensive health insurance program; costs will be shared between employers and employees. The number of doctors per 100,000 (annual average, 1990–99) is 181. The UAE now has 40 public hospitals, compared with only seven in 1970. The Ministry of Health is undertaking a multimillion-dollar program to expand health facilities – hospitals, medical centers, and a trauma center – in the seven emirates. A state-of-the-art general hospital has opened in Abu Dhabi with a projected bed capacity of 143, a trauma unit, and the first home health care program in the UAE. To attract wealthy UAE nationals and expatriates who traditionally have traveled abroad for serious medical care, Dubai is developing Dubai Healthcare City, a hospital free zone that will offer international-standard advanced private health care and provide an academic medical training center; completion is scheduled for 2010.
=== Uzbekistan ===
In the post-Soviet era, the quality of Uzbekistan's health care has declined. Between 1992 and 2003, spending on health care and the ratio of hospital beds to population both decreased by nearly 50 percent, and Russian emigration in that decade deprived the health system of many practitioners. In 2004 Uzbekistan had 53 hospital beds per 10,000 population. Basic medical supplies such as disposable needles, anesthetics, and antibiotics are in very short supply. Although all citizens nominally are entitled to free health care, in the post-Soviet era bribery has become a common way to bypass the slow and limited service of the state system. In the early 2000s, policy has focused on improving primary health care facilities and cutting the cost of inpatient facilities. The state budget for 2006 allotted 11.1 percent to health expenditures, compared with 10.9 percent in 2005.
=== Vietnam ===
The overall quality of health in Vietnam is regarded as good, as reflected by 2005 estimates of life expectancy (70.61 years) and infant mortality (25.95 per 1,000 live births). However, malnutrition is still common in the provinces, and the life expectancy and infant mortality rates are stagnating. In 2001 government spending on health care corresponded to just 0.9 percent of gross domestic product (GDP). Government subsidies covered only about 20 percent of health care expenses, with the remaining 80 percent coming out of individuals' own pockets.
In 1954 the government in the North established a public health system that reached down to the hamlet level. After reunification in 1976, this system was extended to the South. Beginning in the late 1980s, the quality of health care began to decline as a result of budgetary constraints, a shift of responsibility to the provinces, and the introduction of charges. Inadequate funding has led to delays in planned upgrades to water supply and sewage systems. As a result, almost half the population has no access to clean water, a deficiency that promotes such infectious diseases as malaria, dengue fever, typhoid, and cholera. Inadequate funding also has contributed to a shortage of nurses, midwives, and hospital beds. In 2000 Vietnam had only 250,000 hospital beds, or 14.8 beds per 10,000 people, a very low ratio among Asian nations, according to the World Bank.
=== Yemen ===
Despite the significant progress Yemen has made to expand and improve its health care system over the past decade, the system remains severely underdeveloped. Total expenditures on health care in 2002 constituted 3.7 percent of gross domestic product. In that same year, the per capita expenditure for health care was very low, as compared with other Middle Eastern countries – US$58 according to United Nations statistics and US$23 according to the World Health Organization. According to the World Bank, the number of doctors in Yemen rose by an average of more than 7 percent between 1995 and 2000, but as of 2004 there were still only three doctors per 10,000 persons. In 2003 Yemen had only 0.6 hospital beds available per 1,000 persons. Health care services are particularly scarce in rural areas; only 25 percent of rural areas are covered by health services, as compared with 80 percent of urban areas. Emergency services, such as ambulance service and blood banks, are non-existent. Most childhood deaths are caused by illnesses for which vaccines exist or that are otherwise preventable. According to the Joint United Nations Programme on HIV/AIDS, in 2003 an estimated 12,000 people in Yemen were living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS).
== Europe ==
=== Spending ===
Expand the OECD charts below to see the breakdown:
"Government/compulsory": Government spending and compulsory health insurance.
"Voluntary": Voluntary health insurance and private funds such as households’ out-of-pocket payments, NGOs and private corporations.
They are represented by columns starting at zero. They are not stacked. The 2 are combined to get the total.
At the source you can run your cursor over the columns to get the year and the total for that country.
Click the table tab at the source to get 3 lists (one after another) of amounts by country: "Total", "Government/compulsory", and "Voluntary".
=== Belgium ===
As in most countries, the Belgian system divides itself into state and private, though fees are payable in both. A person must have adequate coverage through either the state or private insurance. In the state mutuelle/mutualiteit scheme a person has the ability to choose any doctor, clinic or hospital in any location without referral, according to the patient's needs in much the same way as with private insurance.
General practitioners can be found in private practices or attached to clinics and hospitals. A person is free to consult or register with any of their own choosing. Similarly with specialist consultants. Reimbursements are available for those with insurance, either private or public. If a patient is on a private scheme, or is uninsured, the fee is payable in full at the time of the appointment. The patient then brings, mails or deposits the receipt to his insurance mutuality which then immediately repays the amount. The majority of dentists in Belgium are private, though there are those who accept part-payment on state insurance. As with general practitioners, patients can arrange to see a specialist of their choice at any hospital. Those going into hospital for a planned stay need to take personal care items (such as a towel, soap etc.) with them. In Brussels, the eleven big public hospitals are organized under the Iris association.
The Ministry of Health recognizes homeopathy, acupuncture, osteopathy and chiropractic as reimbursable alternative treatments. Reimbursement is possible only if the practitioner is registered as a qualified doctor. If a call is made to the Emergency services using the old emergency number (100) or the European telephone number (112), an ambulance will transport the patient to the nearest hospital or the best centre suited according to the needs of the patient, for example, a Specialist Burns Unit. Pharmacies are common in Belgium and are marked with a green cross on the street. There is a rota system for pharmacists to open outside of usual hours through the night.
Health care insurance is a part of the Belgian social security system. To enrol, a person must first join a health insurance fund mutuelle (mutualité) or ziekenfonds (mutualiteit) for which an employer's certificate is required if the employer is to contribute to the cost. If employed a person's contributions is automatically deducted from salary. The employer will also pay a contribution. Health insurance funds will reimburse medical costs. The choice of mutual insurer is up to the individual. Most of them are affiliated to a religious or political institution but there is no real difference between them because reimbursement rates are fixed by the Belgian government.
Insurance funds do not always cover the full costs of treatment and typical reimbursement is between half to three-quarters of a typical doctors or specialists visit. A deciding factor here depends on one's job. From people who are unemployed or disabled, receiving other benefits or business-owners receive somewhat less. There is also a "yearly maximum bill" meaning that someone who has paid a certain amount to their doctor/hospital within the year does not have to make any further payment. From this point, any extra is returned from the patient's insurance. In general, the poor, even without reaching the necessary sum, do not pay anything.
=== Bulgaria ===
Bulgaria began overall reform of its antiquated health system, inherited from the communist era, only in 1999. In the 1990s, private medical practices expanded somewhat, but most Bulgarians relied on communist-era public clinics while paying high prices for special care. During that period, national health indicators generally worsened as economic crises substantially decreased health funding. The subsequent health reform program has introduced mandatory employee health insurance through the National Health Insurance Fund (NHIF), which since 2000 has paid a gradually increasing portion of primary health care costs. Employees and employers pay an increasing, mandatory percentage of salaries, with the goal of gradually reducing state support of health care. Private health insurance plays only a supplementary role. The system also has been decentralized by making municipalities responsible for their own health care facilities, and by 2005 most primary care came from private physicians. Pharmaceutical distribution also was decentralized.
In the early 2000s, the hospital system was reduced substantially to limit reliance on hospitals for routine care. Anticipated membership in the European Union (2007) was a major motivation for this trend. Between 2002 and 2003, the number of hospital beds was reduced by 56 percent to 24,300. However, the pace of reduction slowed in the early 2000s; in 2004 some 258 hospitals were in operation, compared with the estimated optimal number of 140. Between 2002 and 2004, health care expenditures in the national budget increased from 3.8 percent to 4.3 percent, with the NHIF accounting for more than 60 percent of annual expenditures.
In the 1990s, the quality of medical research and training decreased seriously because of low funding. In the early 2000s, the emphasis of medical and paramedical training, which was conducted in five medical schools, was preparation of primary-care personnel to overcome shortages resulting from the communist system's long-term emphasis on training specialists. Experts considered that Bulgaria had an adequate supply of doctors but a shortage of other medical personnel. In 2000 Bulgaria had 3.4 doctors, 3.9 nurses, and 0.5 midwives per 1,000 population.
=== Denmark ===
Denmark's health care system has retained the same basic structure since the early 1970s. The administration of hospitals and personnel is dealt with by the Ministry of the Interior, while primary care facilities, health insurance, and community care are the responsibility of the Ministry of Social Affairs. Anyone can go to a physician for no fee and the public health system entitles each Dane to his/her own doctor. Expert medical/surgical aid is available, with a qualified nursing staff. Costs are borne by public authorities, but high taxes contribute to these costs. As of 1999, there were an estimated 3.4 physicians and 4.5 hospital beds per 1,000 people. The number of hospital beds, like that in other EU countries, has undergone a major decline since 1980, from around 40,000 to about 23,000 in 1998/99. Deinstitutionalization of psychiatric patients has contributed significantly to this trend. The ratio of doctors to population, by contrast, has increased during this period.
The total fertility rate in 2000 was 1.7, while the maternal mortality rate was 10 per 100,000 live births as of 1998. Studies show that between 1980 and 1993, 63% of married women (ages 15 to 49) used contraception. As of 2002 cardiovascular diseases and cancer were the leading causes of death. Denmark's cancer rates were the highest in the European Union. In 1999, there were only 12 reported cases of tuberculosis per 100,000 people. As of 1999, the number of people living with HIV/AIDS was estimated at 4,300 and deaths from AIDS that year were estimated at less than 100. HIV prevalence was 0.17 per 100 adults.
Danish citizens may choose between two systems of primary health care: medical care paid for by the government provided by a doctor whom the individual chooses for a year and by those specialists to whom the doctor refers the patient; or complete freedom of choice of any physician or specialist at any time, with state reimbursement of about two-thirds of the cost for medical bills paid directly by the patient. Most Danes opt for the former. All patients receive subsidies on pharmaceuticals and vital drugs; everyone must pay a share of dental bills. As of 1999, total health care expenditure was estimated at 8.4% of GDP.
Responsibility for the public hospital service rests with county authorities. Counties form public hospital regions, each of which is allotted one or two larger hospitals with specialists and two to four smaller hospitals where medical treatment is practically totally paid for by the government. State-appointed medical health officers, responsible to the National Board of Health, are employed to advise local governments on health matters. Public health authorities have waged large-scale campaigns against tuberculosis, venereal diseases, diphtheria, and poliomyelitis. The government-paid guidance and assistance given to mothers of newborn children by public health nurses have resulted in a low infant mortality rate of 4 per 1,000 live births (2000). Medical treatment is government-paid up to school age, when government-paid school medical inspections begin. As of 1999, children up to one year of age were vaccinated against diphtheria, pertussis, and tetanus (99%) and measles (92%). In 2000, life expectancy at birth was 76 years for males and females. The overall death rate was 11 per 1,000 people in 1999.
=== Estonia ===
Healthcare in Estonia is supervised by the Ministry of Social Affairs and funded by general taxation through the National Health Service.
=== Finland ===
In Finland, public medical services at clinics and hospitals are run by the municipalities (local government) and are funded 78% by taxation, 20% by patients through access charges, and by others 2%. Patient access charges are subject to annual caps. For example, GP visits are (€11 per visit with annual €33 cap), hospital outpatient treatment (€22 per visit), a hospital stay, including food, medical care and medicines (€26 per 24 hours, or €12 if in a psychiatric hospital). After a patient has spent €590 per year on public medical services, all treatment and medications thereafter are paid for by the government. Taxation funding is partly local and partly nationally based. Patients can claim re-imbursement of part of their prescription costs from KELA. Finland also has a much smaller private medical sector which accounts for about 14 percent of total health care spending. Only 8% of doctors choose to work in private practice, and some of these also choose to do some work in the public sector. Private sector patients can claim a contribution from KELA towards their private medical costs (including dentistry) if they choose to be treated in the more expensive private sector, or they can join private insurance funds. However, private sector health care is mainly in the primary care sector. There are virtually no private hospitals, the main hospitals being either municipally owned (funded from local taxes) or run by the teaching universities (funded jointly by the municipalities and the national government). In 2005, Finland spent 7.5% of GDP on health care, or US$2,824 per capita. Of that, approximately 78% was government expenditure.
=== France ===
In its 2000 assessment of world health systems, the World Health Organization found that France provided the "best overall health care" in the world. In 2005, France spent 11.2% of GDP on health care, or US$3,926 per capita. Of that, approximately 80% was government expenditure.
In France, most doctors remain in private practice; there are both private and public hospitals. Social Security consists of several public organizations, distinct from the state government, with separate budgets that refunds patients for care in both private and public facilities. It generally refunds patients 70% of most health care costs, and 100% in case of costly or long-term ailments. Supplemental coverage may be bought from private insurers, most of them nonprofit, mutual insurers, to the point that the word "mutuelle" (mutual) has come to be a synonym of supplemental private insurer in common language.
Until recently, social security coverage was restricted to those who contributed to social security (generally, workers, unemployed or retirees), excluding some few poor segments of the population; the government of Lionel Jospin put into place the "universal health coverage" allowing the entire French population to benefit from Health care. In some systems, patients can also take private health insurance but choose to receive care at public hospitals, if allowed by the private insurer. For serious illness, regardless of the insurance regime, the national health system will assume the cost of long-term remedial treatment.
=== Germany ===
Germany has a universal multi-payer system with two main types of health insurance: public or statutory health insurance (gesetzliche Krankenversicherung), and private health insurance (private Krankenversicherung). All German residents must have health insurance. Those who make below a certain income must use the public health insurance, and public health insurers are forced to accept them. Those are compulsorily insured (pflichtversichert), and can choose either the private or the public system. Private health insurance is only available to freelancers, high earners and certain other categories. Those are voluntarily insured (freiwillig versichert). Employers pay for half of their employees' health insurance contributions, while the self-employed must pay the full contribution themselves. Provider compensation rates are negotiated in complex corporatist social bargaining among specified autonomously organized interest groups (e.g. physicians' associations) at the level of federal states. The coverage offered by public health insurers is strictly regulated. They can only refuse to take on the privately insured who are self-employed, or high earners. Small numbers of persons are covered by tax-funded government employee insurance or by social welfare insurance. Private supplementary insurance to the sickness funds of various sorts is available. It adds coverage for extras such as eyeglasses and dental care.
In 2005, Germany spent 10.7% of GDP on health care, or US$3,628 per capita. Of that, approximately 77% was government expenditure.
=== Greece ===
The Greek healthcare system is universal and is ranked as one of the best in the world. In a 2000 World Health Organization report it was ranked 14th in the overall assessment and 11th at quality of service, surpassing countries such as the United Kingdom (18th) and Germany (25th). In 2010 there were 131 hospitals with 35,000 beds in the country, but on 1 July 2011 the Ministry for Health and Social Solidarity announced its proposal to shorten the number to 83 hospitals with 33,000 beds. Greece's healthcare expenditures as a percentage of GDP were 9.6% in 2007 according to a 2011 OECD report, just above the OECD average of 9.5%. The country has the largest number of doctors-to-population ratio of any OECD country.
Life expectancy in Greece is 80.3 years, above the OECD average of 79.5. and among the highest in the world. The same OECD report showed that Greece had the largest percentage of adult daily smokers of any of the 34 OECD members. The country's obesity rate is 18.1%, which is above the OECD average of 15.1% but considerably below the American rate of 27.7%. In 2008 Greece had the highest rate of perceived good health in the OECD, at 98.5%. Infant mortality is one of the lowest in the developed world with a rate of 3.1 deaths/1000 live births.
=== Iceland ===
Healthcare in Iceland is universal. The healthcare system is largely paid for by taxes (85%) and to some extent by service fees (15%) and is administrated by the Ministry of Welfare. A considerable portion of government spending is assigned to healthcare. There is almost no private health insurance in Iceland and no private hospitals.
=== Ireland ===
All persons resident in Ireland are entitled to health care through the public health care system, which is managed by the Health Service Executive and funded by general taxation. A person may be required to pay a subsidised fee for certain health care received; this depends on income, age, illness or disability. All maternity services are however paid for by the government, as well as health care of children under 8 years of age. Emergency care is provided at a cost of €100 for a visit to a hospital Emergency Department.
However, the poor quality of public healthcare has led to a large reliance on private health insurance; over 45% of Irish citizens have private cover. The Irish healthcare system is often described as being "two-tier" or having a "public–private mix." A proposed reform, known as Sláintecare, is being planned; it would provide universal healthcare on the model of the British NHS or other European systems.
=== Italy ===
According to WHO in 2000, Italy had the world's "second overall best" healthcare system in the world, coming after France, and surpassing Spain, Oman and Japan.
In 1978 Italy adopted a tax-funded universal health care system called "National Health Service" (in Italian: Servizio Sanitario Nazionale), which was closely modeled on the British system. The SSN covers general practice (distinct between adult and pediatric practice), outpatient and inpatient treatments, and the cost of most (but not all) drugs and sanitary ware.
The government sets LEA (fundamental levels of care, Livelli essenziali di assistenza in Italian) which cover all necessary treatments, which the state must guarantee to all, paid for by the government, or for a "ticket", a share of the costs (but various categories are exempted).
The public system has also the duty of prevention at place of work and in the general environment.
A private sector also exists, with a minority role in medicine but a principal role in dental health, as most people prefer private dental services.
In Italy the public system has the unique feature of paying general practitioners a fee per capita per year, a salary system, that does not reward repeat visits, testing, and referrals.
While there is a paucity of nurses, Italy has one of the highest doctor per capita ratios at 3.9 doctors per 1,000 patients.
In 2005, Italy spent 8.9% of GDP on health care, or US$2,714 per capita. Of that, approximately 76% was government expenditure.
=== Netherlands ===
Health care in the Netherlands, has since January 2006 been provided by a system of compulsory insurance backed by a risk equalization program so that the insured are not penalized for their age or health status. This is meant to encourage competition between health care providers and insurers. Children under 18 are insured by the government, and special assistance is available to those with limited incomes. In 2005, the Netherlands spent 9.2% of GDP on health care, or US$3,560 per capita. Of that, approximately 65% was government expenditure.
=== Norway ===
Norway has a government run and government financed universal health care system, covering
physical and mental health for all and dental health for children under the age of 16. Hospitals are paid by the state and doctor visit fees are capped at a fairly low rate. Short-term prescriptions for medication are market price, but long-term prescriptions, defined as more than three months a year, are eligible for a large discount. In addition, a yearly cap applies for people with high medical expenses.
Some health care is private. For example, most adults use private dental care, whereas the public system only treats people, for a normal fee, when they have free capacity. Health-related plastic surgery (like burn damage) is covered by the public system, while cosmetic surgery in general is private. There are a number of private psychologists, there are also some private general practice doctors and specialists.
Public health care is financed by a special-purpose income tax on the order of 8–11%, loosely translated as "public benefits fee" (Norwegian: "trygdeavgift og Folketrygden"). This can be considered a mandatory public insurance, covering not only health care but also loss of income during sick leave, public pension, unemployment benefits, benefits for single parents and a few others. The system is supposed to be self-financing from the taxes.
Norwegian citizens living in Norway are automatically covered, even if they never had taxable income. Norwegian citizens living and working abroad (taxable elsewhere and therefore not paying the "public benefits fee" to Norway) are covered for up to one year after they move abroad, and must pay an estimated market cost for public health care services. Non-citizens such as foreign visitors are covered in full.
According to WHO, total health care expenditure in 2005 was 9% of GDP and paid 84% by government, 15% by private out-of-pocket and ≈1% by other private sources.
=== Poland ===
In Poland, healthcare is delivered through a publicly funded healthcare system enshrined in Article 68 of the Constitution of Poland. Employers contribute ~1750PLN per month per employee, people collecting unemployment are covered, and self employed people are compelled to pay either a temporarily lowered or the full 1750PLN rate. Poland's expenditure on healthcare was 6.7% of GDP in 2012 or $900 per capita. The public spending rate for Poland in 2012 was 72% – in-line with the OECD average. A number of private medical complexes also complement public healthcare institutions nationwide.
=== Romania ===
Health care public system has been improved but it is still poor by European standards, and access is limited in rural areas. In 2007 health expenditures were equal to 3.9 percent of gross domestic product. In 2007 there were 2.2 physicians and 6.4 hospital beds per 1,000 people. The system is funded by the National Health Care Insurance Fund, to which employers and employees make mandatory contributions. Private health care system has developed slowly but now consists of 22 private hospitals and more than 240 clinics.
=== Russia ===
Russia in 1991-1993 has changed to a mixed model of health care. Article 41 of the 1993 constitution confirmed a citizen's right to healthcare and medical assistance free of charge in state and municipal health establishments. Private clinics are separate system and it is funded by separate payments of their clients or by private insurance companies via paid voluntary health insurance (known as ДМС - DMS). Only paid clinics allow all types of anonymous medical care. State and municipal health establishments also have the right to provide paid services to any person or in addition to free services.
In all life-threatening cases, emergency medical services, including ambulance vehicles, hospitalization, surgery, etc., are completely free of charge and any documents and name/surname are not required. According to the law "on the basics of health protection of citizens", emergency assistance is provided by a medical organization and a medical employee immediately and free of charge. Refusal to provide it is not allowed. If a medical organization participates in the program of state guarantees of free medical care, it is not allowed to refuse to provide medical care and charge fees. In both of the above cases, a medical employee and a medical organization can be punished under the Criminal Code if the patient has suffered "medium harm" or higher as a result of the lack of aid.
State and municipal health establishments and their workers are funded by multiple sources. The system of compulsory medical insurance (обязательное медицинское страхование, ОМС - obyzatel'noye meditsinskoye strakhovaniye, OMS) is funded by general taxes of individuals and companies via federal, regional and municipal budgets and by employer's additional quasi-tax obligatory payments (officially called "insurance contributions" but collected by Tax Service) via the Federal Compulsory Medical Insurance Fund and Territorial Funds of Russian regions. Medical aid in state and municipal health establishments is available for free to all citizens as well as to foreign permanent residents, foreign temporary residents, stateless persons and refugees regardless of their income or employment status, in all cases with mandatory and free-of-charge pre-conclusion of a contract, confirmed by OMS insurance policy (полис ОМС - polis OMS), with one of the private insurance companies decided to participate in the OMS system. Internal passport of Russia and Individual insurance account number are required for Russian citizens. Identity document and legal status in Russia are required for foreigners and stateless persons. Lack of legal status for foreigners and military service in the Russian Armed Forces for Russian citizens are the only reasons for refusal to obtain or use OMS insurance policy provided that it is not allowed to have two OMS insurance policies. On 1 January 2018, 146.3 million persons were in the OMS system, including 66.4 mln employed and 79.9 mln unemployed persons (the total population of Russia on 1 January 2018 was 146 880 432 persons).
OMS insurance policy is a document confirming the right to receive free medical care. OMS insurance policy or its details are required when applying to state and municipal health establishments. If a person has OMS insurance policy, but does not have it with him, it is not possible to refuse him medical care. A person must choose a permanent establishment for medical care. Health establishment can refuse only in case of overcrowding. Basic services are available for free throughout the country while regional list of services is available for free only in a region of permanent residence. In some cases, free treatment in private clinics (that decided to participate in the OMS system, in very limited cases since this is one of the recent changes to the system), free dental prosthetics and free medications are available through the OMS system.
Introduction in 1993 reform of new free market providers in addition to the state-run institutions intended to promote both efficiency and patient choice. A purchaser-provider split help facilitate the restructuring of care, as resources would migrate to where there was greatest demand, reduce the excess capacity in the hospital sector and stimulate the development of primary care. Russian Prime Minister Vladimir Putin announced a new large-scale health care reform in 2011 and pledged to allocate more than 300 billion rubles ($10 billion) in the next few years to improve health care in the country. He also said that obligatory medical insurance tax paid by companies will increase from current 3.1% to 5.1% starting from 2011.
=== Sweden ===
The Swedish public health system is funded through taxes levied by the county councils, but partly run by private companies. There is a fixed charge of SEK 150 (US$21) for each visit to a doctor or a hospital but some may vary depending on the business itself and cause of admission & desired service whereas prices can vary up to SEK 350 (US$52). Healthcare services that are accepted by the Swedish Board of Health (hälsovårdsnämnden) have "safe net" limits for visitors placed upon them to a maximum SEK 800 (US$111) per year along with prescription medicine from those clinics are also limited to 1,800 SEK (US$249) per year. Government-paid dental care for children under 23 years old is included in the system, and dental care for grown-ups is to a small extent subsidised by it.
Sweden also has a smaller private health care sector, mainly in larger cities or as centers for preventive health care financed by employers.
=== Switzerland ===
In Switzerland, compulsory health insurance covers the costs of medical treatment and hospitalization of the insured. The Swiss healthcare system is a combination of public, subsidized private and totally private healthcare providers, where the insured person has full freedom of choice among the providers in his region. Insurance companies independently set their price points for different age groups, but are forbidden from setting prices based on health risk. In 2000, Switzerland topped all European countries' health care expenditure when calculated as per capita expenditure in US dollar purchasing parity terms.
The Swiss health care system was the last for-profit system in Europe. In the 1990s, after the private carriers began to deny coverage for pre-existing conditions – and when the uninsured population of Switzerland reached 5% – the Swiss held a referendum (1995) and adopted their present system.
=== Turkey ===
Health care in Turkey used to be dominated by a centralized state system run by the Ministry of Health. In 2003 the government introduced a sweeping health reform program aimed at increasing the ratio of private to state health provision and making health care available to a larger share of the population. Information from the Turkish Statistical Institute states that 76.3 billions of Turkish liras are being spent in healthcare, with 79.6% of funding coming from the Sosyal Güvenlik Kurumu and most of the remainder (15.4%) coming from out-of-pocket payments. There are 27.954 medical institutions, one doctor for 587 people and 2.54 beds for 1000 people.
=== United Kingdom ===
The four countries of the United Kingdom have separate but co-operating public health care systems that were created in 1948: in England the public health system is known as the National Health Service, in Scotland it is known as NHS Scotland, in Wales as NHS Wales (GIG Cymru), and in Northern Ireland it is called Health and Social Care in Northern Ireland. All four provide state-paid healthcare to all UK residents, paid for from general taxation. Though the public systems dominate, private health care and a wide variety of alternative and complementary treatments are available for those who have private health insurance or are willing to pay directly themselves.
One difference between the four public health care systems is the patient cost for prescriptions. Wales, Northern Ireland and Scotland have recently abolished, or are in the process of abolishing, all prescription charges, while England (with the exception of birth control pills, which are paid for by the state) continues to charge patients who are between 18 and 60 years old a fixed prescription fee of £9.15 per item or yearly prepayment of £105.90, unless they are exempt because of certain medical conditions (including cancer) or are on low income. Since health care delivery is a devolved matter, considerable differences are developing between the systems in each of the countries.
==== England ====
Health care in England is mainly provided by the National Health Service (NHS), a public body that provides healthcare to all permanent residents in England, that is free at the point of use. The body is one of four forming the UK National Health Service as health is a devolved matter; there are differences with the provisions for healthcare elsewhere in the United Kingdom, and in England it is overseen by NHS England. Though the public system dominates healthcare provision in England, private health care and a wide variety of alternative and complementary treatments are available for those willing and able to pay.
The Secretary of State for Health and Social Care is a senior minister of the Crown within the Government of the United Kingdom, and leads the Department of Health and Social Care with responsibility for England's NHS. The Secretary serves as the principal adviser to the Prime Minister of the United Kingdom on all health matters.
==== Scotland ====
The National Health Service (NHS) in Scotland was created by the National Health Service (Scotland) Act 1947 in 1948 at the same time the NHS was created for England and Wales. Scotland's NHS remains a separate body from the other public health systems in the UK which can lead to confusion from patients when "cross-border" or emergency care is involved. Primary and secondary care are integrated in Scotland. Unlike in England, NHS trusts do not exist in Scotland. Instead, healthcare is provided through fourteen regional health boards. These health boards are further subdivided into Health and Social Care Partnerships. The Scottish Ambulance Service is the pan-Scotland board responsible for prehospital care provision and transport of patients between the mainland and the Scottish Islands. The ambulance service is supported by the Emergency Medical Retrieval Service and BASICS Scotland.
Scotland spent over £12 billion on healthcare in 2015/16 which accounted for 40% of the Scottish Government's total budget. The NHS in Scotland consists of approximately 161,000 employees, 9.2% of whom are medical or dental doctors, 42.9% nurses and midwives, 18.2% administrative services, 3.9% healthcare scientists, and the remaining 25.8% in various other medical services. In the past several years, healthcare costs have been rising in Scotland. Despite this, Scots have a generally favorable view of their NHS service with 61% of the population either very or quite satisfied with the service.
==== Northern Ireland ====
The Health and Social Care service was created by the Parliament of Northern Ireland in 1948 after the Beveridge Report.
From 1948 to 1974, hospitals in the region were managed by the Northern Ireland Hospitals Authority and hospital management committees, and then transferred to four health and social services boards, along with responsibility for social care. The pattern of local government in the region was of 26 single-tier local authorities which, apart from Belfast, covered small populations ranging from 13,000 to 90,000 and were not considered an adequate base for the provision of personal social services.
The Health and Social Care (Reform) Act (Northern Ireland) 2009 led to a reorganisation of health and social care delivery in Northern Ireland, reducing the number of organisations involved. This Act established the Health and Social Care Board and five Health and Social Care Trusts which are responsible for the delivery of primary, secondary and community health care. The act also established five local commissioning groups which work in parallel with the health and social care trusts.
==== Wales ====
Healthcare in Wales is mainly provided by the Welsh public health service, NHS Wales. NHS Wales provides healthcare to all permanent residents that is free at the point of need and paid for from general taxation. Health is a matter that is devolved, and considerable differences are now developing between the public healthcare systems in the different countries of the United Kingdom, collectively the National Health Service (NHS). Though the public system dominates healthcare provision, private health care and a wide variety of alternative and complementary treatments are available for those willing to pay.
Unlike in England, NHS prescriptions are free to everyone registered with a GP in Wales (although those on low incomes, under 18, and under 60 do get prescriptions for free in England). Initially administered by the UK Government, since 1999 NHS Wales has been funded and managed by the Welsh Government.
== Oceania ==
=== Australia ===
In Australia the current system, known as Medicare, was created in 1984. It coexists with a private health system. All legal permanent residents are entitled to government-paid public hospital care. Treatment by private doctors is also paid by the government when the doctor direct bills the Health Department (Bulk Billing). Medicare is funded partly by a 1.5% income tax levy (with exceptions for low-income earners), but mostly out of general revenue. An additional levy of 1% is imposed on high-income earners without private health insurance. There is a means tested 30% subsidy on private health insurance. As well as Medicare, there is a separate Pharmaceutical Benefits Scheme under which listing and a government subsidy is dependent on expert evaluation of the comparative cost-effectiveness of new pharmaceuticals. In 2005, Australia spent 8.8% of GDP on health care, or US$3,181 per capita. Of that, approximately 67% was government expenditure.
=== New Zealand ===
In New Zealand hospitals are public and treat citizens or permanent residents, with the fees paid by the government, and are managed by district health boards. Under the Labour coalition governments (1999–2008), there were plans to make primary health care available with charges paid for by the government. At present government subsidies exist in health care. The cost of visiting a GP ranges from government-paid to $45.00 for children and from government-paid to $75.00 for adults under the current subsidies. This system is funded by taxes. The New Zealand government agency Pharmac subsidizes certain pharmaceuticals depending upon their category. Co-payments exist, however these are lower if the user has a Community Services Card or High User Health Card. In 2005, New Zealand spent 8.9% of GDP on health care, or US$2,403 per capita. Of that, approximately 77% was government expenditure.
== See also ==
List of countries and dependencies by number of physicians
Tobacco control laws by country
International comparisons
== References == | Wikipedia/Health_care_systems_by_country |
An academic medical centre (AMC), variously also known as academic health science centre, academic health science system, or academic health science partnership, is an educational and healthcare institute formed by the grouping of a health professional school (such as a medical school) with an affiliated teaching hospital or hospital network.
AMCs are intended to ensure that medical research breakthroughs lead to direct clinical benefits for patients. The organisational structures that comprise an AMCs can take a variety of forms, ranging from simple partnerships to, less frequently, fully integrated organisations with a single management board. There are AMCs operating in a number of countries including Australia, Canada, Ireland, Japan, the Netherlands, Qatar, Singapore, Sweden, the United Kingdom and the United States.
== Australia ==
Health Translation Queensland (Brisbane, Australia)
Melbourne Academic Centre for Health (Melbourne, Australia)]
Monash Partners Academic Health Science Centre (Melbourne, Australia)
South Australian Academic Health Science and Translation Centre (Adelaide, Australia)
Sydney Health Partners (Sydney, Australia)
Sydney Partnership for Health, Education, Research & Enterprise (Sydney, Australia)
Western Australian Health Translation Network (Perth, Australia)
Tropical Australian Academic Health Centre (North Queensland, Australia)
== Canada ==
Hamilton Health Sciences (Hamilton, Ontario)
St. Joseph's Healthcare Hamilton (Hamilton, Ontario)
Health Sciences North (Sudbury, Ontario)
Kingston Health Sciences Centre (Kingston, Ontario)
London Health Sciences Centre (London, Ontario)
McGill University Health Centre (Montreal, Quebec)
Centre Hospitalier de l'Université de Montréal (Montreal, Quebec)
Sunnybrook Health Sciences Centre (Toronto, Ontario)
The Ottawa Hospital (Ottawa, Ontario)
Thunder Bay Regional Health Sciences Centre (Thunder Bay, Ontario)
Trillium Health Partners (Mississauga, Ontario)
University Health Network (Toronto, Ontario)
Unity Health Toronto (Toronto, Ontario)
Vancouver Hospital and Health Sciences Centre (Vancouver, British Columbia)
Winnipeg Health Sciences Centre (Winnipeg, Manitoba)
== United Kingdom ==
Bristol Health Partners, Bristol
Cambridge University Health Partners, Cambridge
Imperial College Academic Health Science Centre, London
King's Health Partners, London
Manchester Academic Health Science Centre, Manchester
Newcastle Health Innovation Partners, Newcastle upon Tyne
Oxford Academic Health Partners, Oxford
South East Wales Academic Health Science Partnership, Cardiff
UCLPartners, London
== United States ==
Albany Medical Center, Albany Medical College, Albany, New York
Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado
BJC HealthCare, St. Louis, Missouri
Boston Medical Center, Boston University, Boston, Massachusetts
Cedars-Sinai Medical Center, Los Angeles, California
Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio
Dartmouth-Hitchcock Medical Center, Geisel School of Medicine, Lebanon, New Hampshire
Duke University Medical Center (Durham, North Carolina)
Geisinger Medical Center (Danville, Pennsylvania)
Georgetown University Medical Center (Washington, D.C.)
Intermountain Medical Center (Salt Lake City, Utah)
Johns Hopkins Hospital (Baltimore, Maryland)
Keck Hospital of USC (Los Angeles, California)
Loma Linda University Health (Loma Linda, California)
Massachusetts General Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center, Harvard Medical School (Boston, Massachusetts)
Mayo Clinic, Mayo Clinic College of Medicine and Science (Rochester, Minnesota)
Medical University of South Carolina, Charleston, South Carolina
Memorial Medical Center and St. John's Hospital (Springfield, Illinois)
National Academy of Medicine
National Institutes of Health
New York–Presbyterian Hospital, Columbia University and Cornell University, New York City
NYU Langone Medical Center, New York University, New York City
Ohio State University Wexner Medical Center, Ohio State University (Columbus, Ohio)
Oregon Health & Science University, (Portland, Oregon)
OSF Saint Francis Medical Center and the Children's Hospital of Illinois (Peoria, Illinois)
Providence Alaska Medical Center (Anchorage, Alaska)
Robert Wood Johnson University Hospital, Robert Wood Johnson Medical School (New Brunswick, New Jersey)
Stony Brook University Hospital, Stony Brook University- State University of New York, Stony Brook, New York
SUNY Downstate Medical Center, SUNY Downstate Health Sciences University, Brooklyn, New York City
Temple University Hospital, Temple University (Philadelphia, Pennsylvania)
Texas Medical Center (Houston, Texas)
Texas Tech University Health Sciences Center (Lubbock, Texas)
Texas Tech University Health Sciences Center El Paso (El Paso, Texas)
Thomas Jefferson University Hospital, Thomas Jefferson University (Philadelphia, Pennsylvania)
Tufts Medical Center (Boston, Massachusetts)
UC Davis Medical Center (Sacramento, California)
UC Irvine Medical Center (Orange, California)
UCLA Health System (Los Angeles, California)
UC San Diego Health (La Jolla, California)
UCSF Medical Center (San Francisco, California)
Uniformed Services University, (Bethesda, Maryland)
University of Alabama at Birmingham, Alabama
University of Chicago Medical Center, University of Chicago, Chicago, Illinois
University of Connecticut Health Center, University of Connecticut, Farmington, Connecticut
University of Cincinnati Medical Center (Cincinnati, Ohio)
University of Florida Health (UF Health) (Gainesville and Jacksonville, Florida)
University Hospitals Cleveland Medical Center (Cleveland, Ohio)
University of Kentucky HealthCare (Lexington, Kentucky)
University of Louisville Health Science Center (Louisville, Kentucky)
University of Miami Health System (UHealth) (Miami, Florida)
University of Michigan Health System, University of Michigan, Ann Arbor, Michigan
University of Mississippi Medical Center, Mississippi
University of North Carolina Hospitals (Chapel Hill, North Carolina)
University of Pennsylvania Health System, (Philadelphia, Pennsylvania)
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
University of Tennessee Health Science Center (Memphis, Tennessee)
University of Texas Medical Branch (Galveston, Texas)
University of Texas Southwestern Medical Center (Dallas, Texas)
University of Utah Hospital, University of Utah (Salt Lake City, Utah)
University of Vermont Medical Center, University of Vermont (Burlington, Vermont)
University of Virginia Health System, Charlottesville, Virginia
University of Wisconsin Hospital and Clinics, Madison, Wisconsin
Upstate University Hospital, Norton College of Medicine – State University of New York (Syracuse, New York)
UW Medicine, University of Washington (Seattle, Washington)
Vanderbilt University Medical Center, Nashville, Tennessee
Vidant Medical Center, Brody School of Medicine at East Carolina University (Greenville, North Carolina)
VCU Medical Center, Virginia Commonwealth University, Richmond, Virginia
Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
Westchester Medical Center, Valhalla, New York
Yale-New Haven Hospital, Yale University, New Haven, Connecticut
== Other countries ==
Academic Health System Universitas Indonesia (Jakarta, Indonesia)
Academic Health System Universitas Gadjah Mada (Yogyakarta, Indonesia)
Kyushu University Academic Medical Center (Fukuoka, Japan)
Dublin Academic Medical Centre (Dublin, Ireland)
Hamad Medical Corporation (Doha, Qatar)
Karolinska Institutet (Stockholm, Sweden)
Leiden University Medical Center (Leiden, the Netherlands)
National University Health System (Singapore)
Radboud University Nijmegen Medical Centre (Nijmegen, the Netherlands)
SingHealth Duke-NUS Academic Medical Center, Singapore
== See also ==
List of university hospitals
Medical school
Teaching hospital
== References ==
== External links ==
Official website – Association of Academic Health Centers | Wikipedia/Academic_health_science_centre |
Practice theory (or praxeology, theory of social practices) is a body of social theory within anthropology and sociology that explains society and culture as the result of structure and individual agency. Practice theory emerged in the late 20th century and was first outlined in the work of the French sociologist Pierre Bourdieu.
Practice theory developed in reaction to the Structuralist school of thought, developed by social scientists including Claude Lévi-Strauss, who saw human behavior and organization systems as products of innate universal structures that reflect the mental structures of humans. Structuralist theory asserted that these structures governed all human societies.
Practice theory is also built on the concept of agency. For practice theorists, the individual agent is an active participant in the formation and reproduction of their social world.
== History ==
In 1972, French sociologist Pierre Bourdieu published Esquisse d'une théorie de la pratique (published in English as Outline of a Theory of Practice in 1977), which emerged from his ethnographic field work in French-occupied Algeria among the Kabyle at the outbreak of the Algerian War of Independence. The original goal of this work was to understand Algerian culture and its internal rules and laws in an effort to understand the conflict. Bourdieu later rejected the idea that culture and social life can be reduced to the acting-out of rules and the primacy of social structures over the individual. Instead, Bourdieu argues, culture and society are better understood as the product of dynamic interactions between social actors and structure. Anthony Giddens and Michel de Certeau were also foundational to the theory in the late 1970s and 1980s.
== Premise ==
Practices are conceptualized as "what people do," or an individual's performance carried out in everyday life. Bourdieu's theory of practice sets up a relationship between structure and the habitus and practice of the individual agent, dealing with the "relationship between the objective structures and the cognitive and motivating structures which they produce and which tend to reproduce them". What is perceived and experienced as culture is the result of dynamic interaction of internal and external structures, individual performance (practice), and strategy (strategy is based on existing structures, but it exists from the actions of individuals seeking to pursue their own interests). Bourdieu describes structure as the "products of historical practices and are constantly reproduced and transformed by historical practices whose productive principle is itself the product of the structures which it consequently tends to reproduce." According to practice theory, social actors are not just shaped by their social world, they shape it as well. Since Bourdieu's formulation, practice theory has been expanded by sociologists, anthropologists, international relation scholars, and feminist scholars, among others.
=== habitus ===
Along with practices, habitus is a key concept in practice theory. Bourdieu defined habitus as "a structuring structure, which organizes practices and the perception of practices" (1984: 170). First proposed by philosopher Marcel Mauss, Bourdieu uses the term habitus to refer to patterns of thought and behavior which are deeply internalized structures. Habitus is composed of social conventions, rules, values, etc., that guide our everyday practices. These mental structures are representations of the external social structures people interact with on a daily basis. They inform our practice and give meaning to the world and are what drives us to behave in accordance with social and cultural conventions. Habitus is also influenced by external individual forces, such as confronting a new social norm, or a new way of doing things. Like structure, habitus is also the product of historical events.
The embodied component of the habitus is the hexis. It is manifested as an individual's gait, gesture, postures, accent etc. A closely related notion to Bourdieu's habitus is Michel Foucault's concept of 'discipline'. Like habitus, discipline 'is structure and power that have been impressed on the body forming permanent dispositions'. In contrast to Bourdieu, though, Foucault laid particular emphasis on the violence through which modern regimes (e.g. prisons and asylums) are used as a form of social control.
=== doxa ===
Another important concept to practice theory are doxa, which are the internalized societal or field-specific presuppositions that 'go without saying' and are not up for negotiation. The doxa is a constructed vision of reality so naturalized that it appears to be the only vision of reality. It is the learned, fundamental, deep-founded, unconscious beliefs and values that are taken as self-evident universals and inform an agent's actions and thoughts within a particular field. An example is the belief that a year must have 365 days or that days must be 24 hours long. The field represents a structured social space with its own rules, schemes of domination, legitimate opinions. Bourdieu uses the concept of field instead of analyzing societies solely in terms of classes. For example, fields in modern societies include arts, education, politics, law and economy. Cultural capital is also part of practice theory and is directly related to strategy. It is the intangible assets that enable actors to mobilize cultural authority/power as part of strategy e.g., e.g., competencies, education, intellect, style of speech, dress, social networks,. This is important in terms of an individual's strategy. A later addition to practice theory is structuration, coined by Anthony Giddens.
== In anthropology and sociology ==
Cultural anthropologist Sherry Ortner defines practice theory as "a theory of history. It is a theory of how social beings, with their diverse motives and their diverse intentions, make and transform in which they live." Ortner developed what she terms "cultural schemas" to explain society's structural contradictions and agency. Her engagement with practice theory focuses on how agents "react to, cope with, or actively appropriate" external structures. These responses of agents are bound or enabled by the cultural schemas which are often rooted in the contradictions of society's structure and habitus of the agent. Agents create broader social narratives practices unique to their specific culture from multiple schemas. The many available to agents schemas woven to a social narrative help to "give society its distinctiveness and coherence" Ortner's agent is "loosely structured", their practice is constituted of how they respond to the schemas.
British sociologist Anthony Giddens extended practice theory with his concept of structuration. Structuration is based on his previous work on the Duality of structure, the idea that the agency of social actors and structure are inseparable and co-create one another. Agency, according to Giddens, is neither free will or the intentionality of actions, but the capacity of the agent to act. The agency of individuals is constrained and enabled by structure. In turn, structure is created, transformed, and reproduced through the actions of agents. Giddens identified two forms of consciousness that inform the knowledgeable agent's actions: practical consciousness and discursive consciousness.
== Influenced ==
=== Gender theory ===
Judith Butler's work on gender and sex is based on performance and practice theory. In Gender Trouble (1990) and "Performative Acts and Gender Constitution" (1988), Butler advances their concept of gender performativity. They argue that all gender and sexual identities are constructs. These identities are not real or innately natural and they do not express any inner reality. Instead, gender and sexuality are constituted by performance, meaning the everyday repetition of acts that reaffirm these identities. The individual performs gender and then that identity is validated by society.
=== Communities of practice and learning as practice ===
Jean Lave and Etienne Wenger draw from practice theory to conceptualize communities of practice as a place of learning. Roddick and Ann B. Stahl summarize communities of practice as involving "embodied action and continuously renewed relations between understanding and experience, more and less skilled practitioners, and the objects and communities with which practitioners interact."
Communities of practice center the relationship of the agent, the activity engaged in, and community, which are co-created and relational to one another. Learning and apprenticeship within practice communities are processes that place individual experience and everyday practice in active discourse with the broader context of their society. According to Wenger and Lave, learning is "situated" through practice of novices and expert practitioners. More recent approaches extend the scope to issues such as agency, material, and interaction.
== Other theories of practice ==
=== Schatzki's theory of practice ===
In the 1990s, Theodore Schatzki developed an alternative theory of practice in Social Practices (1996) and The Site of the Social (2002). His basic premise is that people do what makes sense for them to do and derives from the work of Martin Heidegger and Ludwig Wittgenstein. Practices make up people's 'horizon of intelligibility.' Schatzki defines practices as 'open-ended spatial-temporal manifolds of actions' (Schatzki, 2005, p. 471) and also as 'sets of hierarchically organized doings/sayings, tasks and projects'. Such practices consist of four main elements: (1) practical understanding – "knowing how to X, knowing how to identify X-ings, and knowing how to prompt as well as respond to X-ings" (idem, p. 77); (2) rules – "explicit formulations, principles, precepts, and instructions that enjoin, direct or remonstrate people to perform specific actions" (idem, p. 79); (3) teleo-affective structure – "a range of normativized and hierarchically ordered ends, projects and tasks, to varying degrees allied with normativized emotions and even mood" (idem, p. 80); and (4) general understanding.
== Other important theorists ==
William Hanks
Sherry Ortner
Marshall Sahlins
Andreas Reckwitz
Jean Lave
Davide Nicolini
Elizabeth Shove
Silvia Gherardi
Michel Foucault
Bruno Latour
Michel Callon
== References ==
== Bibliography ==
Ahearn, Laura M. (2001). "Language and Agency". Annual Review of Anthropology. 30 (1). Annual Reviews: 109–137. doi:10.1146/annurev.anthro.30.1.109. ISSN 0084-6570.
Archer, Margaret S. (2003). Structure, agency and the internal conversation. Cambridge University Press.
Bourdieu, Pierre [1972] 1977. Outline of a Theory of Practice. Trans. Richard Nice. Cambridge University Press.
Bourdieu, Pierre ( 1990). The Logic of Practice. Trans. Richard Nice. Polity Press.
Calhoun, Craig, Edward LiPuma, and Moishe Postone (1993). Bourdieu: critical perspectives. University of Chicago Press.
de Certeau, Michel (1984). "Foucault and Bourdieu". In The practice of everyday life. Trans. Rendall S. F.University of California Press.
Gherardi, S. (2014). How to Conduct a Practice-Based Study: Problems and Methods. Edward Elgar Pub.
Gherardi, S. (2006). Organizational Knowledge: The Texture of Workplace Learning. Wiley.Giddens, Anthony (1979). Central problems in social theory: Action, structure, and contradiction in social analysis. University of California Press.
Giddens, Anthony (1984). The Constitution Of Society: Outline Of A Theory Of Structuration. Polity Press.
Moore, Jerry D.(2000). Visions of culture: An introduction to anthropological theories and theorists. Rowman Altamira.
Morris, Rosalind C. (1995). "All made up: Performance theory and the new anthropology of sex and gender". Annual review of anthropology. 24 (1): 567–592.
Nicolini, Davide. Practice theory, work, and organization: An introduction. OUP Oxford, 2012
Ortner, Sherry B. (2006). Anthropology and social theory : culture, power, and the acting subject. Durham: Duke University Press. ISBN 978-0-8223-8845-6. OCLC 262341007.
Ortner, Sherry B. (2006). "Introduction: Updating Practice Theory". Anthropology and social theory : culture, power, and the acting subject. Durham: Duke University Press. doi:10.2307/j.ctv11hppcg.4. ISBN 978-0-8223-8845-6. OCLC 262341007.
Roddick, Andrew P.; Stahl, Anne B. "Introduction: Knowledge in Motion".(2016). Knowledge in motion : constellations of learning across time and place. Ed.Andrew Roddick and Anne P. Stahl. Tucson: The University of Arizona Press.
Turner, Stephen (1994). The Social Theory of Practices: Tradition, Tacit Knowledge, and Presuppositions. University of Chicago Press. | Wikipedia/Practice_theory |
In psychology, trait theory (also called dispositional theory) is an approach to the study of human personality. Trait theorists are primarily interested in the measurement of traits, which can be defined as habitual patterns of behavior, thought, and emotion. According to this perspective, traits are aspects of personality that are relatively stable over time, differ across individuals (e.g. some people are outgoing whereas others are not), are relatively consistent over situations, and influence behaviour. Traits are in contrast to states, which are more transitory dispositions. Traits such as extraversion vs. introversion are measured on a spectrum, with each person placed somewhere along it.
Trait theory suggests that some natural behaviours may give someone an advantage in a position of leadership.
There are two approaches to define traits: as internal causal properties or as purely descriptive summaries. The internal causal definition states that traits influence our behaviours, leading us to do things in line with that trait. On the other hand, traits as descriptive summaries are descriptions of our actions that do not try to infer causality.
== History ==
American psychologist Gordon Allport was an early pioneer in the study of traits. This early work was viewed as the beginning of the modern psychological study of personality. He also referred to traits within his work as dispositions. In his approach, "cardinal" traits are those that dominate and shape a person's behavior; their ruling passions/obsessions, such as a need for money, fame etc. By contrast, "central" traits such as honesty are characteristics found in some degree in every person – and finally "secondary" traits are those seen only in certain circumstances (such as particular likes or dislikes that a very close friend may know), which are included to provide a complete picture of human complexity.
A wide variety of alternative theories and scales were later developed, including:
Raymond Cattell's 16PF Questionnaire
J. P. Guilford's Structure of Intellect
Henry Murray's System of Needs
Timothy Leary's Interpersonal circumplex
Myers–Briggs Type Indicator
Gray's Biopsychological theory of personality
Currently, two general approaches are the most popular:
Eysenck Personality Questionnaire, (EPQ) ("the three-factor model"). Using factor analysis, Hans Eysenck suggested that personality is reducible to three major traits: neuroticism, extraversion, and psychoticism.
Big Five personality traits, ("the five-factor model"). Many psychologists currently believe that five factors are sufficient: neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness.
== Trait theory in cross-cultural use ==
Cultures are widely known and accepted as being different in varying degrees. This can make the study of personality difficult as meaning and the expression of traits may be different within cultural groups. Trait theory uses a hierarchy of traits in order to separate culture from the traits; it can be said the culture is ignored in order to focus on the individual traits and how they are connected to the individual. Gordon Allport's trait theory not only served as a foundational approach within personality psychology, but also is continued to be viewed and discussed by other disciplines such as anthropology because of how he approached culture within trait theory.
Trait theory tends to focus on the individual over the situation in which they are in. This focus has relaxed within modern studies allowing for a consideration of the external factors outside of the self. As the focus becomes more relaxed (but still prominent as it is a main part of the theory) research expands.
== Comparing EPQ and Big Five ==
=== Testing methodology, and factors ===
Both the EPQ and Big Five approaches extensively use self-report questionnaires. The factors are intended to be orthogonal (uncorrelated), though there are often small positive correlations between factors. The five factor model in particular has been criticized for losing the orthogonal structure between factors. British psychologist Hans Eysenck has argued that fewer factors are superior to a larger number of partly related ones. Although these two approaches are comparable because of the use of factor analysis to construct hierarchical taxonomies, they differ in the organization and number of factors.
Whatever the causes, psychoticism marks the two approaches apart, as the five factor model contains no such trait. Moreover, psychoticism, unlike any of the other factors in either approach, does not fit a normal distribution curve. Indeed, scores are rarely high, thus skewing a normal distribution. However, when they are high, there is considerable overlap with psychiatric conditions such as antisocial and schizoid personality disorders. Similarly, high scorers on neuroticism are more susceptible to sleep and psychosomatic disorders. Five factor approaches can also predict future mental disorders.
=== Lower-order factors ===
There are two higher-order factors that both taxonomies clearly share: extraversion and neuroticism. Both approaches broadly accept that extraversion is associated with sociability and positive affect, whereas neuroticism is associated with emotional instability and negative affect.
Many lower-order factors, or facets, are similar between the two taxonomies. For instance, both approaches contain factors for sociability/gregariousness, for activity levels, and for assertiveness within the higher order factor extraversion. However, there are differences too. First, the three-factor approach contains nine lower-order factors and the five-factor approach has six.
Eysenck's psychoticism factor incorporates some of the polar opposites of the lower order factors of openness, agreeableness and conscientiousness. A high scorer on tough-mindedness in psychoticism would score low on tender-mindedness in agreeableness. Most of the differences between the taxonomies stem from the three factor model's emphasis on fewer high-order factors.
=== Causality ===
Although both major trait models are descriptive, only the three-factor model offers a detailed causal explanation. Eysenck suggests that different personality traits are caused by the properties of the brain, which themselves are the result of genetic factors. In particular, the three-factor model identifies the reticular system and the limbic system in the brain as key components that mediate cortical arousal and emotional responses respectively. Eysenck advocates that extraverts have low levels of cortical arousal and introverts have high levels, leading extraverts to seek out more stimulation from socializing and being venturesome. Moreover, Eysenck surmised that there would be an optimal level of arousal, after which inhibition would occur and that this would be different for each person.
In a similar vein, the three-factor approach theorizes that neuroticism is mediated by levels of arousal in the limbic system and that individual differences arise because of variable activation thresholds between people. Therefore, highly neurotic people when presented with minor stressors, will exceed this threshold, whereas people low in neuroticism will not exceed normal activation levels, even when presented with large stressors. By contrast, proponents of the five-factor approach assume a role of genetics and environment but offer no explicit causal explanation.
Given this emphasis on biology in the three-factor approach, it would be expected that the third trait, psychoticism, would have a similar explanation. However, the causal properties of this state are not well defined. Eysenck has suggested that psychoticism is related to testosterone levels and is an inverse function of the serotonergic system, but he later revised this, linking it instead to the dopaminergic system.
== List of personality traits ==
After examining thousands of personality measures and numerous personality trait frameworks, researchers have created "super-frameworks" that aim to encapsulate all personality traits into a single model (e.g., Pan-Hierarchical Five Factor Model). These models also sometimes identify measures that can be used to measure traits/constructs in the models.
== See also ==
16 Personality Factors – Self-report personality test
Alternative five model of personality – personality model with five factors: impulsive sensation seeking, neuroticism–anxiety, aggression–hostility, sociability, and activityPages displaying wikidata descriptions as a fallback
Big Five personality traits – Personality model consisting of five broad dimensions
Cultural schema theory – Cognitive theory at the cultural level
HEXACO model of personality structure – Six-dimensional model of human personality
Minnesota Multiphasic Personality Inventory – Standardized psychometric measure of psychopathology and personality
NEO-PI – Big Five personality trait inventoryPages displaying short descriptions of redirect targets
Personality psychology – Branch of psychology focused on personality
Social investment theory
Szondi test – 1935 discredited psychological test
Trait activation theory – Theory of personality-job fit
== References == | Wikipedia/Trait_theory |
Empirical research is research using empirical evidence. It is also a way of gaining knowledge by means of direct and indirect observation or experience. Empiricism values some research more than other kinds. Empirical evidence (the record of one's direct observations or experiences) can be analyzed quantitatively or qualitatively. Quantifying the evidence or making sense of it in qualitative form, a researcher can answer empirical questions, which should be clearly defined and answerable with the evidence collected (usually called data). Research design varies by field and by the question being investigated. Many researchers combine qualitative and quantitative forms of analysis to better answer questions that cannot be studied in laboratory settings, particularly in the social sciences and in education.
In some fields, quantitative research may begin with a research question (e.g., "Does listening to vocal music during the learning of a word list have an effect on later memory for these words?") which is tested through experimentation. Usually, the researcher has a certain theory regarding the topic under investigation. Based on this theory, statements or hypotheses will be proposed (e.g., "Listening to vocal music has a negative effect on learning a word list."). From these hypotheses, predictions about specific events are derived (e.g., "People who study a word list while listening to vocal music will remember fewer words on a later memory test than people who study a word list in silence."). These predictions can then be tested with a suitable experiment. Depending on the outcomes of the experiment, the theory on which the hypotheses and predictions were based will be supported or not, or may need to be modified and then subjected to further testing.
== History ==
The experimental method has evolved over the ages, with many scientists contributing to its foundation and development. In ancient times, Greek philosophers, such as Aristotle, relied on observation and rational inference in their studies. Aristotle, for example, rejected exclusive reliance on logical deduction, emphasizing the importance of observation in understanding nature.
During the Middle Ages, Muslim scientists significantly advanced the experimental method. Jabir ibn Hayyan, known as the father of chemistry, introduced experimental methodology into chemistry and developed chemical processes such as crystallization, calcination, and distillation. He also discovered important acids like sulfuric and nitric acid, expanding the possibilities of chemical experiments. The famous optics scientist Alhazen (Ibn al-Haytham) was among the first to rely on experimentation in studying light and vision. In his book Book of Optics, he employed a scientific method based on observation, experimentation, and mathematical proof, making him a pioneer of the modern scientific method.
These scientific approaches were transmitted to Europe through translations, influencing the development of modern scientific methodology. European scientists, such as Francis Bacon, were inspired by the works of Muslim scholars in refining the experimental method. The researcher Robert Briffault, in his book Making of Humanity, states:
"It was under their successors at Oxford School (that is, successors to the Muslims of Spain) that Roger Bacon learned Arabic and Arabic Sciences. Neither Roger Bacon nor later namesake has any title to be credited with having introduced the experimental method. Roger Bacon was no more than one of apostles of Muslim Science and Method to Christian Europe".
== Terminology ==
The term empirical was originally used to refer to certain ancient Greek practitioners of medicine who rejected adherence to the dogmatic doctrines of the day, preferring instead to rely on the observation of phenomena as perceived in experience. Later empiricism referred to a theory of knowledge in philosophy which adheres to the principle that knowledge arises from experience and evidence gathered specifically using the senses. In scientific use, the term empirical refers to the gathering of data using only evidence that is observable by the senses or in some cases using calibrated scientific instruments. What early philosophers described as empiricist and empirical research have in common is the dependence on observable data to formulate and test theories and come to conclusions.
== Usage ==
The researcher attempts to describe accurately the interaction between the instrument (or the human senses) and the entity being observed. If instrumentation is involved, the researcher is expected to calibrate his/her instrument by applying it to known standard objects and documenting the results before applying it to unknown objects. In other words, it describes the research that has not taken place before and their results.
In practice, the accumulation of evidence for or against any particular theory involves planned research designs for the collection of empirical data, and academic rigor plays a large part of judging the merits of research design. Several typologies for such designs have been suggested, one of the most popular of which comes from Campbell and Stanley. They are responsible for popularizing the widely cited distinction among pre-experimental, experimental, and quasi-experimental designs and are staunch advocates of the central role of randomized experiments in educational research.
=== Scientific research ===
Accurate analysis of data using standardized statistical methods in scientific studies is critical to determining the validity of empirical research. Statistical formulas such as regression, uncertainty coefficient, t-test, chi square, and various types of ANOVA (analyses of variance) are fundamental to forming logical, valid conclusions. If empirical data reach significance under the appropriate statistical formula, the research hypothesis is supported. If not, the null hypothesis is supported (or, more accurately, not rejected), meaning no effect of the independent variable(s) was observed on the dependent variable(s).
The result of empirical research using statistical hypothesis testing is never proof. It can only support a hypothesis, reject it, or do neither. These methods yield only probabilities. Among scientific researchers, empirical evidence (as distinct from empirical research) refers to objective evidence that appears the same regardless of the observer. For example, a thermometer will not display different temperatures for each individual who observes it. Temperature, as measured by an accurate, well calibrated thermometer, is empirical evidence. By contrast, non-empirical evidence is subjective, depending on the observer. Following the previous example, observer A might truthfully report that a room is warm, while observer B might truthfully report that the same room is cool, though both observe the same reading on the thermometer. The use of empirical evidence negates this effect of personal (i.e., subjective) experience or time.
The varying perception of empiricism and rationalism shows concern with the limit to which there is dependency on experience of sense as an effort of gaining knowledge. According to rationalism, there are a number of different ways in which sense experience is gained independently for the knowledge and concepts. According to empiricism, sense experience is considered as the main source of every piece of knowledge and the concepts.
In general, rationalists are known for the development of their own views following two different way. First, the key argument can be placed that there are cases in which the content of knowledge or concepts end up outstripping the information. This outstripped information is provided by the sense experience (Hjørland, 2010, 2). Second, there is construction of accounts as to how reasoning helps in the provision of addition knowledge about a specific or broader scope. Empiricists are known to be presenting complementary senses related to thought.
First, there is development of accounts of how there is provision of information by experience that is cited by rationalists. This is insofar for having it in the initial place. At times, empiricists tend to be opting skepticism as an option of rationalism. If experience is not helpful in the provision of knowledge or concept cited by rationalists, then they do not exist (Pearce, 2010, 35). Second, empiricists have a tendency of attacking the accounts of rationalists, while considering reasoning to be an important source of knowledge or concepts.
The overall disagreement between empiricists and rationalists shows major concerns about how knowledge is gained with respect to the sources of knowledge and concepts. In some of the cases, disagreement on the point of gaining knowledge results in the provision of conflicting responses to other aspects as well. There might be a disagreement in the overall feature of warrant, while limiting the knowledge and thought. Empiricists are known for sharing the view that there is no existence of innate knowledge and rather that is derivation of knowledge out of experience. These experiences are either reasoned using the mind or sensed through the five senses human possess (Bernard, 2011, 5). On the other hand, rationalists are known to be sharing the view that there is existence of innate knowledge and this is different for the objects of innate knowledge being chosen.
In order to follow rationalism, there must be adoption of one of the three claims related to the theory that are deduction or intuition, innate knowledge, and innate concept. The more there is removal of concept from mental operations and experience, there can be performance over experience with increased plausibility in being innate. Further ahead, empiricism in context with a specific subject provides a rejection of the corresponding version related to innate knowledge and deduction or intuition (Weiskopf, 2008, 16). Insofar as there is acknowledgement of concepts and knowledge within the area of subject, the knowledge has major dependence on experience through human senses.
== Empirical cycle ==
A.D. de Groot's empirical cycle:
Observation: The observation of a phenomenon and inquiry concerning its causes.
Induction: The formulation of hypotheses - generalized explanations for the phenomenon.
Deduction: The formulation of experiments that will test the hypotheses (i.e. confirm them if true, refute them if false).
Testing: The procedures by which the hypotheses are tested and data are collected.
Evaluation: The interpretation of the data and the formulation of a theory - an abductive argument that presents the results of the experiment as the most reasonable explanation for the phenomenon.
== See also ==
Case study
Fact
Field research
Scientific method
== References ==
== External links ==
The dictionary definition of empirical research at Wiktionary
Some Key Concepts for the Design and Review of Empirical Research Archived 2021-04-16 at the Wayback Machine | Wikipedia/Empirical_method |
Particulate inheritance is a pattern of inheritance discovered by Mendelian genetics theorists, such as William Bateson, Ronald Fisher or Gregor Mendel himself, showing that phenotypic traits can be passed from generation to generation through "discrete particles" known as genes, which can keep their ability to be expressed while not always appearing in a descending generation.
== Scientific developments leading up to the theory ==
Early in the 19th century, scientists had already recognized that Earth has been inhabited by living creatures for a very long time. On the other hand, they did not understand what mechanisms actually drove biological diversity. They also did not understand how physical traits are inherited from one generation to the next. Blending inheritance was the common ideal at the time, but was later discredited by the experiments of Gregor Mendel. Mendel proposed the theory of particulate inheritance by using pea plants (Pisum sativum) to explain how variation can be inherited and maintained over time.
=== Blending model versus particulate model ===
Blending model:
Offspring are a blend of both parents (i.e. in modern terms, alleles would blend together to form a completely new allele)
The characteristics of the blended offspring are passed on to the next generation
Variation is washed out over time
Particulate model:
Offspring are a combination of both parents
The characteristics of both parents are passed on to the next generation as separate entities
Variation is maintained over time
== Mendel's methods ==
=== Mendel's laws ===
Since Mendel used experimental methods to devise his particulate inheritance theory, he developed three basic laws of inheritance: the Law of Segregation, the Law of Independent Assortment, and the Law of Dominance:
==== Law of segregation ====
Mendel's experiment with tall and short pea plants demonstrates how each individual plant has two particles called alleles. When a pea plant produces gametes (reproductive cells), it segregates one allele to each one.
==== Law of independent assortment ====
The law states that when the parents differ from each other in two or more pairs of contrasting characters, the inheritance of one pair of characters is independent to that of the other pair of characters.
==== Law of dominance ====
In the pea plants, Mendel observed that the "T" allele (dominant) masked the effects of the "t" allele (recessive). The terms "dominant" and "recessive" are used for the masking and the covered allele, respectively. All offspring from this cross are heterozygotes in terms of their genotypes. They also are tall (because the allele for tall masks the allele for short) in terms of their "phenotype".
== Fisher ==
In a 1918 publication titled "The Supposition of Mendelian Inheritance Among Close Relatives," R.A. Fisher showed that particulate inheritance was capable of generating the vast amount of variation we see among closely related individuals. This helped to reconcile the Biometric and Mendelian schools of thought at the time, and was an important step in the modern synthesis.
== Notes ==
== References ==
Campbell, N. E. & Reece, J. B. (2002). Biology (6th ed.). San Francisco: Benjamin Cummings.
"Particulate inheritance." BioEd Online. Retrieved 3-5-2009 from BioEd Online Slides | Wikipedia/Particulate_inheritance_theory |
Present-day climate change includes both global warming—the ongoing increase in global average temperature—and its wider effects on Earth’s climate system. Climate change in a broader sense also includes previous long-term changes to Earth's climate. The current rise in global temperatures is driven by human activities, especially fossil fuel burning since the Industrial Revolution. Fossil fuel use, deforestation, and some agricultural and industrial practices release greenhouse gases. These gases absorb some of the heat that the Earth radiates after it warms from sunlight, warming the lower atmosphere. Carbon dioxide, the primary gas driving global warming, has increased in concentration by about 50% since the pre-industrial era to levels not seen for millions of years.
Climate change has an increasingly large impact on the environment. Deserts are expanding, while heat waves and wildfires are becoming more common. Amplified warming in the Arctic has contributed to thawing permafrost, retreat of glaciers and sea ice decline. Higher temperatures are also causing more intense storms, droughts, and other weather extremes. Rapid environmental change in mountains, coral reefs, and the Arctic is forcing many species to relocate or become extinct. Even if efforts to minimize future warming are successful, some effects will continue for centuries. These include ocean heating, ocean acidification and sea level rise.
Climate change threatens people with increased flooding, extreme heat, increased food and water scarcity, more disease, and economic loss. Human migration and conflict can also be a result. The World Health Organization calls climate change one of the biggest threats to global health in the 21st century. Societies and ecosystems will experience more severe risks without action to limit warming. Adapting to climate change through efforts like flood control measures or drought-resistant crops partially reduces climate change risks, although some limits to adaptation have already been reached. Poorer communities are responsible for a small share of global emissions, yet have the least ability to adapt and are most vulnerable to climate change.
Many climate change impacts have been observed in the first decades of the 21st century, with 2024 the warmest on record at +1.60 °C (2.88 °F) since regular tracking began in 1850. Additional warming will increase these impacts and can trigger tipping points, such as melting all of the Greenland ice sheet. Under the 2015 Paris Agreement, nations collectively agreed to keep warming "well under 2 °C". However, with pledges made under the Agreement, global warming would still reach about 2.8 °C (5.0 °F) by the end of the century. Limiting warming to 1.5 °C would require halving emissions by 2030 and achieving net-zero emissions by 2050.
There is widespread support for climate action worldwide. Fossil fuel use can be phased out by conserving energy and switching to energy sources that do not produce significant carbon pollution. These energy sources include wind, solar, hydro, and nuclear power. Cleanly generated electricity can replace fossil fuels for powering transportation, heating buildings, and running industrial processes. Carbon can also be removed from the atmosphere, for instance by increasing forest cover and farming with methods that capture carbon in soil.
== Terminology ==
Before the 1980s it was unclear whether the warming effect of increased greenhouse gases was stronger than the cooling effect of airborne particulates in air pollution. Scientists used the term inadvertent climate modification to refer to human impacts on the climate at this time. In the 1980s, the terms global warming and climate change became more common, often being used interchangeably. Scientifically, global warming refers only to increased surface warming, while climate change describes both global warming and its effects on Earth's climate system, such as precipitation changes.
Climate change can also be used more broadly to include changes to the climate that have happened throughout Earth's history. Global warming—used as early as 1975—became the more popular term after NASA climate scientist James Hansen used it in his 1988 testimony in the U.S. Senate. Since the 2000s, climate change has increased usage. Various scientists, politicians and media may use the terms climate crisis or climate emergency to talk about climate change, and may use the term global heating instead of global warming.
== Global temperature rise ==
=== Temperatures prior to present-day global warming ===
Over the last few million years the climate cycled through ice ages. One of the hotter periods was the Last Interglacial, around 125,000 years ago, where temperatures were between 0.5 °C and 1.5 °C warmer than before the start of global warming. This period saw sea levels 5 to 10 metres higher than today. The most recent glacial maximum 20,000 years ago was some 5–7 °C colder. This period has sea levels that were over 125 metres (410 ft) lower than today.
Temperatures stabilized in the current interglacial period beginning 11,700 years ago. This period also saw the start of agriculture. Historical patterns of warming and cooling, like the Medieval Warm Period and the Little Ice Age, did not occur at the same time across different regions. Temperatures may have reached as high as those of the late 20th century in a limited set of regions. Climate information for that period comes from climate proxies, such as trees and ice cores.
=== Warming since the Industrial Revolution ===
Around 1850 thermometer records began to provide global coverage.
Between the 18th century and 1970 there was little net warming, as the warming impact of greenhouse gas emissions was offset by cooling from sulfur dioxide emissions. Sulfur dioxide causes acid rain, but it also produces sulfate aerosols in the atmosphere, which reflect sunlight and cause global dimming. After 1970, the increasing accumulation of greenhouse gases and controls on sulfur pollution led to a marked increase in temperature.
Ongoing changes in climate have had no precedent for several thousand years. Multiple independent datasets all show worldwide increases in surface temperature, at a rate of around 0.2 °C per decade. The 2014–2023 decade warmed to an average 1.19 °C [1.06–1.30 °C] compared to the pre-industrial baseline (1850–1900). Not every single year was warmer than the last: internal climate variability processes can make any year 0.2 °C warmer or colder than the average. From 1998 to 2013, negative phases of two such processes, Pacific Decadal Oscillation (PDO) and Atlantic Multidecadal Oscillation (AMO) caused a short slower period of warming called the "global warming hiatus". After the "hiatus", the opposite occurred, with 2024 well above the recent average at more than +1.5 °C. This is why the temperature change is defined in terms of a 20-year average, which reduces the noise of hot and cold years and decadal climate patterns, and detects the long-term signal.: 5
A wide range of other observations reinforce the evidence of warming. The upper atmosphere is cooling, because greenhouse gases are trapping heat near the Earth's surface, and so less heat is radiating into space. Warming reduces average snow cover and forces the retreat of glaciers. At the same time, warming also causes greater evaporation from the oceans, leading to more atmospheric humidity, more and heavier precipitation. Plants are flowering earlier in spring, and thousands of animal species have been permanently moving to cooler areas.
==== Differences by region ====
Different regions of the world warm at different rates. The pattern is independent of where greenhouse gases are emitted, because the gases persist long enough to diffuse across the planet. Since the pre-industrial period, the average surface temperature over land regions has increased almost twice as fast as the global average surface temperature. This is because oceans lose more heat by evaporation and oceans can store a lot of heat. The thermal energy in the global climate system has grown with only brief pauses since at least 1970, and over 90% of this extra energy has been stored in the ocean. The rest has heated the atmosphere, melted ice, and warmed the continents.
The Northern Hemisphere and the North Pole have warmed much faster than the South Pole and Southern Hemisphere. The Northern Hemisphere not only has much more land, but also more seasonal snow cover and sea ice. As these surfaces flip from reflecting a lot of light to being dark after the ice has melted, they start absorbing more heat. Local black carbon deposits on snow and ice also contribute to Arctic warming. Arctic surface temperatures are increasing between three and four times faster than in the rest of the world. Melting of ice sheets near the poles weakens both the Atlantic and the Antarctic limb of thermohaline circulation, which further changes the distribution of heat and precipitation around the globe.
=== Future global temperatures ===
The World Meteorological Organization estimates there is almost a 50% chance of the five-year average global temperature exceeding +1.5 °C between 2024 and 2028. The IPCC expects the 20-year average to exceed +1.5 °C in the early 2030s.
The IPCC Sixth Assessment Report (2021) included projections that by 2100 global warming is very likely to reach 1.0–1.8 °C under a scenario with very low emissions of greenhouse gases, 2.1–3.5 °C under an intermediate emissions scenario,
or 3.3–5.7 °C under a very high emissions scenario. The warming will continue past 2100 in the intermediate and high emission scenarios, with future projections of global surface temperatures by year 2300 being similar to millions of years ago.
The remaining carbon budget for staying beneath certain temperature increases is determined by modelling the carbon cycle and climate sensitivity to greenhouse gases. According to UNEP, global warming can be kept below 1.5 °C with a 50% chance if emissions after 2023 do not exceed 200 gigatonnes of CO2. This corresponds to around 4 years of current emissions. To stay under 2.0 °C, the carbon budget is 900 gigatonnes of CO2, or 16 years of current emissions.
== Causes of recent global temperature rise ==
The climate system experiences various cycles on its own which can last for years, decades or even centuries. For example, El Niño events cause short-term spikes in surface temperature while La Niña events cause short term cooling. Their relative frequency can affect global temperature trends on a decadal timescale. Other changes are caused by an imbalance of energy from external forcings. Examples of these include changes in the concentrations of greenhouse gases, solar luminosity, volcanic eruptions, and variations in the Earth's orbit around the Sun.
To determine the human contribution to climate change, unique "fingerprints" for all potential causes are developed and compared with both observed patterns and known internal climate variability. For example, solar forcing—whose fingerprint involves warming the entire atmosphere—is ruled out because only the lower atmosphere has warmed. Atmospheric aerosols produce a smaller, cooling effect. Other drivers, such as changes in albedo, are less impactful.
=== Greenhouse gases ===
Greenhouse gases are transparent to sunlight, and thus allow it to pass through the atmosphere to heat the Earth's surface. The Earth radiates it as heat, and greenhouse gases absorb a portion of it. This absorption slows the rate at which heat escapes into space, trapping heat near the Earth's surface and warming it over time.
While water vapour (≈50%) and clouds (≈25%) are the biggest contributors to the greenhouse effect, they primarily change as a function of temperature and are therefore mostly considered to be feedbacks that change climate sensitivity. On the other hand, concentrations of gases such as CO2 (≈20%), tropospheric ozone, CFCs and nitrous oxide are added or removed independently from temperature, and are therefore considered to be external forcings that change global temperatures.
Before the Industrial Revolution, naturally-occurring amounts of greenhouse gases caused the air near the surface to be about 33 °C warmer than it would have been in their absence. Human activity since the Industrial Revolution, mainly extracting and burning fossil fuels (coal, oil, and natural gas), has increased the amount of greenhouse gases in the atmosphere. In 2022, the concentrations of CO2 and methane had increased by about 50% and 164%, respectively, since 1750. These CO2 levels are higher than they have been at any time during the last 14 million years. Concentrations of methane are far higher than they were over the last 800,000 years.
Global human-caused greenhouse gas emissions in 2019 were equivalent to 59 billion tonnes of CO2. Of these emissions, 75% was CO2, 18% was methane, 4% was nitrous oxide, and 2% was fluorinated gases. CO2 emissions primarily come from burning fossil fuels to provide energy for transport, manufacturing, heating, and electricity. Additional CO2 emissions come from deforestation and industrial processes, which include the CO2 released by the chemical reactions for making cement, steel, aluminum, and fertilizer. Methane emissions come from livestock, manure, rice cultivation, landfills, wastewater, and coal mining, as well as oil and gas extraction. Nitrous oxide emissions largely come from the microbial decomposition of fertilizer.
While methane only lasts in the atmosphere for an average of 12 years, CO2 lasts much longer. The Earth's surface absorbs CO2 as part of the carbon cycle. While plants on land and in the ocean absorb most excess emissions of CO2 every year, that CO2 is returned to the atmosphere when biological matter is digested, burns, or decays. Land-surface carbon sink processes, such as carbon fixation in the soil and photosynthesis, remove about 29% of annual global CO2 emissions. The ocean has absorbed 20 to 30% of emitted CO2 over the last two decades. CO2 is only removed from the atmosphere for the long term when it is stored in the Earth's crust, which is a process that can take millions of years to complete.
=== Land surface changes ===
Around 30% of Earth's land area is largely unusable for humans (glaciers, deserts, etc.), 26% is forests, 10% is shrubland and 34% is agricultural land. Deforestation is the main land use change contributor to global warming, as the destroyed trees release CO2, and are not replaced by new trees, removing that carbon sink. Between 2001 and 2018, 27% of deforestation was from permanent clearing to enable agricultural expansion for crops and livestock. Another 24% has been lost to temporary clearing under the shifting cultivation agricultural systems. 26% was due to logging for wood and derived products, and wildfires have accounted for the remaining 23%. Some forests have not been fully cleared, but were already degraded by these impacts. Restoring these forests also recovers their potential as a carbon sink.
Local vegetation cover impacts how much of the sunlight gets reflected back into space (albedo), and how much heat is lost by evaporation. For instance, the change from a dark forest to grassland makes the surface lighter, causing it to reflect more sunlight. Deforestation can also modify the release of chemical compounds that influence clouds, and by changing wind patterns. In tropic and temperate areas the net effect is to produce significant warming, and forest restoration can make local temperatures cooler. At latitudes closer to the poles, there is a cooling effect as forest is replaced by snow-covered (and more reflective) plains. Globally, these increases in surface albedo have been the dominant direct influence on temperature from land use change. Thus, land use change to date is estimated to have a slight cooling effect.
=== Other factors ===
==== Aerosols and clouds ====
Air pollution, in the form of aerosols, affects the climate on a large scale. Aerosols scatter and absorb solar radiation. From 1961 to 1990, a gradual reduction in the amount of sunlight reaching the Earth's surface was observed. This phenomenon is popularly known as global dimming, and is primarily attributed to sulfate aerosols produced by the combustion of fossil fuels with heavy sulfur concentrations like coal and bunker fuel. Smaller contributions come from black carbon (from combustion of fossil fuels and biomass), and from dust. Globally, aerosols have been declining since 1990 due to pollution controls, meaning that they no longer mask greenhouse gas warming as much.
Aerosols also have indirect effects on the Earth's energy budget. Sulfate aerosols act as cloud condensation nuclei and lead to clouds that have more and smaller cloud droplets. These clouds reflect solar radiation more efficiently than clouds with fewer and larger droplets. They also reduce the growth of raindrops, which makes clouds more reflective to incoming sunlight. Indirect effects of aerosols are the largest uncertainty in radiative forcing.
While aerosols typically limit global warming by reflecting sunlight, black carbon in soot that falls on snow or ice can contribute to global warming. Not only does this increase the absorption of sunlight, it also increases melting and sea-level rise. Limiting new black carbon deposits in the Arctic could reduce global warming by 0.2 °C by 2050. The effect of decreasing sulfur content of fuel oil for ships since 2020 is estimated to cause an additional 0.05 °C increase in global mean temperature by 2050.
==== Solar and volcanic activity ====
As the Sun is the Earth's primary energy source, changes in incoming sunlight directly affect the climate system. Solar irradiance has been measured directly by satellites, and indirect measurements are available from the early 1600s onwards. Since 1880, there has been no upward trend in the amount of the Sun's energy reaching the Earth, in contrast to the warming of the lower atmosphere (the troposphere). The upper atmosphere (the stratosphere) would also be warming if the Sun was sending more energy to Earth, but instead, it has been cooling.
This is consistent with greenhouse gases preventing heat from leaving the Earth's atmosphere.
Explosive volcanic eruptions can release gases, dust and ash that partially block sunlight and reduce temperatures, or they can send water vapour into the atmosphere, which adds to greenhouse gases and increases temperatures. These impacts on temperature only last for several years, because both water vapour and volcanic material have low persistence in the atmosphere. volcanic CO2 emissions are more persistent, but they are equivalent to less than 1% of current human-caused CO2 emissions. Volcanic activity still represents the single largest natural impact (forcing) on temperature in the industrial era. Yet, like the other natural forcings, it has had negligible impacts on global temperature trends since the Industrial Revolution.
==== Climate change feedbacks ====
The climate system's response to an initial forcing is shaped by feedbacks, which either amplify or dampen the change. Self-reinforcing or positive feedbacks increase the response, while balancing or negative feedbacks reduce it. The main reinforcing feedbacks are the water-vapour feedback, the ice–albedo feedback, and the net cloud feedback. The primary balancing mechanism is radiative cooling, as Earth's surface gives off more heat to space in response to rising temperature. In addition to temperature feedbacks, there are feedbacks in the carbon cycle, such as the fertilizing effect of CO2 on plant growth. Feedbacks are expected to trend in a positive direction as greenhouse gas emissions continue, raising climate sensitivity.
These feedback processes alter the pace of global warming. For instance, warmer air can hold more moisture in the form of water vapour, which is itself a potent greenhouse gas. Warmer air can also make clouds higher and thinner, and therefore more insulating, increasing climate warming. The reduction of snow cover and sea ice in the Arctic is another major feedback, this reduces the reflectivity of the Earth's surface in the region and accelerates Arctic warming. This additional warming also contributes to permafrost thawing, which releases methane and CO2 into the atmosphere.
Around half of human-caused CO2 emissions have been absorbed by land plants and by the oceans. This fraction is not static and if future CO2 emissions decrease, the Earth will be able to absorb up to around 70%. If they increase substantially, it'll still absorb more carbon than now, but the overall fraction will decrease to below 40%. This is because climate change increases droughts and heat waves that eventually inhibit plant growth on land, and soils will release more carbon from dead plants when they are warmer. The rate at which oceans absorb atmospheric carbon will be lowered as they become more acidic and experience changes in thermohaline circulation and phytoplankton distribution. Uncertainty over feedbacks, particularly cloud cover, is the major reason why different climate models project different magnitudes of warming for a given amount of emissions.
== Modelling ==
A climate model is a representation of the physical, chemical and biological processes that affect the climate system. Models include natural processes like changes in the Earth's orbit, historical changes in the Sun's activity, and volcanic forcing. Models are used to estimate the degree of warming future emissions will cause when accounting for the strength of climate feedbacks. Models also predict the circulation of the oceans, the annual cycle of the seasons, and the flows of carbon between the land surface and the atmosphere.
The physical realism of models is tested by examining their ability to simulate current or past climates. Past models have underestimated the rate of Arctic shrinkage and underestimated the rate of precipitation increase. Sea level rise since 1990 was underestimated in older models, but more recent models agree well with observations. The 2017 United States-published National Climate Assessment notes that "climate models may still be underestimating or missing relevant feedback processes". Additionally, climate models may be unable to adequately predict short-term regional climatic shifts.
A subset of climate models add societal factors to a physical climate model. These models simulate how population, economic growth, and energy use affect—and interact with—the physical climate. With this information, these models can produce scenarios of future greenhouse gas emissions. This is then used as input for physical climate models and carbon cycle models to predict how atmospheric concentrations of greenhouse gases might change. Depending on the socioeconomic scenario and the mitigation scenario, models produce atmospheric CO2 concentrations that range widely between 380 and 1400 ppm.
== Impacts ==
=== Environmental effects ===
The environmental effects of climate change are broad and far-reaching, affecting oceans, ice, and weather. Changes may occur gradually or rapidly. Evidence for these effects comes from studying climate change in the past, from modelling, and from modern observations. Since the 1950s, droughts and heat waves have appeared simultaneously with increasing frequency. Extremely wet or dry events within the monsoon period have increased in India and East Asia. Monsoonal precipitation over the Northern Hemisphere has increased since 1980. The rainfall rate and intensity of hurricanes and typhoons is likely increasing, and the geographic range likely expanding poleward in response to climate warming. Frequency of tropical cyclones has not increased as a result of climate change.
Global sea level is rising as a consequence of thermal expansion and the melting of glaciers and ice sheets. Sea level rise has increased over time, reaching 4.8 cm per decade between 2014 and 2023. Over the 21st century, the IPCC projects 32–62 cm of sea level rise under a low emission scenario, 44–76 cm under an intermediate one and 65–101 cm under a very high emission scenario. Marine ice sheet instability processes in Antarctica may add substantially to these values, including the possibility of a 2-meter sea level rise by 2100 under high emissions.
Climate change has led to decades of shrinking and thinning of the Arctic sea ice. While ice-free summers are expected to be rare at 1.5 °C degrees of warming, they are set to occur once every three to ten years at a warming level of 2 °C. Higher atmospheric CO2 concentrations cause more CO2 to dissolve in the oceans, which is making them more acidic. Because oxygen is less soluble in warmer water, its concentrations in the ocean are decreasing, and dead zones are expanding.
=== Tipping points and long-term impacts ===
Greater degrees of global warming increase the risk of passing through 'tipping points'—thresholds beyond which certain major impacts can no longer be avoided even if temperatures return to their previous state. For instance, the Greenland ice sheet is already melting, but if global warming reaches levels between 1.7 °C and 2.3 °C, its melting will continue until it fully disappears. If the warming is later reduced to 1.5 °C or less, it will still lose a lot more ice than if the warming was never allowed to reach the threshold in the first place. While the ice sheets would melt over millennia, other tipping points would occur faster and give societies less time to respond. The collapse of major ocean currents like the Atlantic meridional overturning circulation (AMOC), and irreversible damage to key ecosystems like the Amazon rainforest and coral reefs can unfold in a matter of decades. The collapse of the AMOC would be a severe climate catastrophe, resulting in a cooling of the Northern Hemisphere.
The long-term effects of climate change on oceans include further ice melt, ocean warming, sea level rise, ocean acidification and ocean deoxygenation. The timescale of long-term impacts are centuries to millennia due to CO2's long atmospheric lifetime. The result is an estimated total sea level rise of 2.3 metres per degree Celsius (4.2 ft/°F) after 2000 years. Oceanic CO2 uptake is slow enough that ocean acidification will also continue for hundreds to thousands of years. Deep oceans (below 2,000 metres (6,600 ft)) are also already committed to losing over 10% of their dissolved oxygen by the warming which occurred to date. Further, the West Antarctic ice sheet appears committed to practically irreversible melting, which would increase the sea levels by at least 3.3 m (10 ft 10 in) over approximately 2000 years.
=== Nature and wildlife ===
Recent warming has driven many terrestrial and freshwater species poleward and towards higher altitudes. For instance, the range of hundreds of North American birds has shifted northward at an average rate of 1.5 km/year over the past 55 years. Higher atmospheric CO2 levels and an extended growing season have resulted in global greening. However, heatwaves and drought have reduced ecosystem productivity in some regions. The future balance of these opposing effects is unclear. A related phenomenon driven by climate change is woody plant encroachment, affecting up to 500 million hectares globally. Climate change has contributed to the expansion of drier climate zones, such as the expansion of deserts in the subtropics. The size and speed of global warming is making abrupt changes in ecosystems more likely. Overall, it is expected that climate change will result in the extinction of many species.
The oceans have heated more slowly than the land, but plants and animals in the ocean have migrated towards the colder poles faster than species on land. Just as on land, heat waves in the ocean occur more frequently due to climate change, harming a wide range of organisms such as corals, kelp, and seabirds. Ocean acidification makes it harder for marine calcifying organisms such as mussels, barnacles and corals to produce shells and skeletons; and heatwaves have bleached coral reefs. Harmful algal blooms enhanced by climate change and eutrophication lower oxygen levels, disrupt food webs and cause great loss of marine life. Coastal ecosystems are under particular stress. Almost half of global wetlands have disappeared due to climate change and other human impacts. Plants have come under increased stress from damage by insects.
=== Humans ===
The effects of climate change are impacting humans everywhere in the world. Impacts can be observed on all continents and ocean regions, with low-latitude, less developed areas facing the greatest risk. Continued warming has potentially "severe, pervasive and irreversible impacts" for people and ecosystems. The risks are unevenly distributed, but are generally greater for disadvantaged people in developing and developed countries.
==== Health and food ====
The World Health Organization calls climate change one of the biggest threats to global health in the 21st century. Scientists have warned about the irreversible harms it poses. Extreme weather events affect public health, and food and water security. Temperature extremes lead to increased illness and death. Climate change increases the intensity and frequency of extreme weather events. It can affect transmission of infectious diseases, such as dengue fever and malaria. According to the World Economic Forum, 14.5 million more deaths are expected due to climate change by 2050. 30% of the global population currently live in areas where extreme heat and humidity are already associated with excess deaths. By 2100, 50% to 75% of the global population would live in such areas.
While total crop yields have been increasing in the past 50 years due to agricultural improvements, climate change has already decreased the rate of yield growth. Fisheries have been negatively affected in multiple regions. While agricultural productivity has been positively affected in some high latitude areas, mid- and low-latitude areas have been negatively affected. According to the World Economic Forum, an increase in drought in certain regions could cause 3.2 million deaths from malnutrition by 2050 and stunting in children. With 2 °C warming, global livestock headcounts could decline by 7–10% by 2050, as less animal feed will be available. If the emissions continue to increase for the rest of century, then over 9 million climate-related deaths would occur annually by 2100.
==== Livelihoods and inequality ====
Economic damages due to climate change may be severe and there is a chance of disastrous consequences. Severe impacts are expected in South-East Asia and sub-Saharan Africa, where most of the local inhabitants are dependent upon natural and agricultural resources. Heat stress can prevent outdoor labourers from working. If warming reaches 4 °C then labour capacity in those regions could be reduced by 30 to 50%. The World Bank estimates that between 2016 and 2030, climate change could drive over 120 million people into extreme poverty without adaptation.
Inequalities based on wealth and social status have worsened due to climate change. Major difficulties in mitigating, adapting to, and recovering from climate shocks are faced by marginalized people who have less control over resources. Indigenous people, who are subsistent on their land and ecosystems, will face endangerment to their wellness and lifestyles due to climate change. An expert elicitation concluded that the role of climate change in armed conflict has been small compared to factors such as socio-economic inequality and state capabilities.
While women are not inherently more at risk from climate change and shocks, limits on women's resources and discriminatory gender norms constrain their adaptive capacity and resilience. For example, women's work burdens, including hours worked in agriculture, tend to decline less than men's during climate shocks such as heat stress.
==== Climate migration ====
Low-lying islands and coastal communities are threatened by sea level rise, which makes urban flooding more common. Sometimes, land is permanently lost to the sea. This could lead to statelessness for people in island nations, such as the Maldives and Tuvalu. In some regions, the rise in temperature and humidity may be too severe for humans to adapt to. With worst-case climate change, models project that almost one-third of humanity might live in Sahara-like uninhabitable and extremely hot climates.
These factors can drive climate or environmental migration, within and between countries. More people are expected to be displaced because of sea level rise, extreme weather and conflict from increased competition over natural resources. Climate change may also increase vulnerability, leading to "trapped populations" who are not able to move due to a lack of resources.
== Reducing and recapturing emissions ==
Climate change can be mitigated by reducing the rate at which greenhouse gases are emitted into the atmosphere, and by increasing the rate at which carbon dioxide is removed from the atmosphere. To limit global warming to less than 1.5 °C global greenhouse gas emissions needs to be net-zero by 2050, or by 2070 with a 2 °C target. This requires far-reaching, systemic changes on an unprecedented scale in energy, land, cities, transport, buildings, and industry.
The United Nations Environment Programme estimates that countries need to triple their pledges under the Paris Agreement within the next decade to limit global warming to 2 °C. An even greater level of reduction is required to meet the 1.5 °C goal. With pledges made under the Paris Agreement as of 2024, there would be a 66% chance that global warming is kept under 2.8 °C by the end of the century (range: 1.9–3.7 °C, depending on exact implementation and technological progress). When only considering current policies, this raises to 3.1 °C. Globally, limiting warming to 2 °C may result in higher economic benefits than economic costs.
Although there is no single pathway to limit global warming to 1.5 or 2 °C, most scenarios and strategies see a major increase in the use of renewable energy in combination with increased energy efficiency measures to generate the needed greenhouse gas reductions. To reduce pressures on ecosystems and enhance their carbon sequestration capabilities, changes would also be necessary in agriculture and forestry, such as preventing deforestation and restoring natural ecosystems by reforestation.
Other approaches to mitigating climate change have a higher level of risk. Scenarios that limit global warming to 1.5 °C typically project the large-scale use of carbon dioxide removal methods over the 21st century. There are concerns, though, about over-reliance on these technologies, and environmental impacts.
Solar radiation modification (SRM) is a proposal for reducing global warming by reflecting some sunlight away from Earth and back into space. Because it does not reduce greenhouse gas concentrations, it would not address ocean acidification and is not considered mitigation. SRM should be considered only as a supplement to mitigation, not a replacement for it, due to risks such as rapid warming if it were abruptly stopped and not restarted. The most-studied approach is stratospheric aerosol injection. SRM could reduce global warming and some of its impacts, though imperfectly. It poses environmental risks, such as changes to rainfall patterns, as well as political challenges, such as who would decide whether to use it.
=== Clean energy ===
Renewable energy is key to limiting climate change. For decades, fossil fuels have accounted for roughly 80% of the world's energy use. The remaining share has been split between nuclear power and renewables (including hydropower, bioenergy, wind and solar power and geothermal energy). Fossil fuel use is expected to peak in absolute terms prior to 2030 and then to decline, with coal use experiencing the sharpest reductions. Renewables represented 86% of all new electricity generation installed in 2023. Other forms of clean energy, such as nuclear and hydropower, currently have a larger share of the energy supply. However, their future growth forecasts appear limited in comparison.
While solar panels and onshore wind are now among the cheapest forms of adding new power generation capacity in many locations, green energy policies are needed to achieve a rapid transition from fossil fuels to renewables. To achieve carbon neutrality by 2050, renewable energy would become the dominant form of electricity generation, rising to 85% or more by 2050 in some scenarios. Investment in coal would be eliminated and coal use nearly phased out by 2050.
Electricity generated from renewable sources would also need to become the main energy source for heating and transport. Transport can switch away from internal combustion engine vehicles and towards electric vehicles, public transit, and active transport (cycling and walking). For shipping and flying, low-carbon fuels would reduce emissions. Heating could be increasingly decarbonized with technologies like heat pumps.
There are obstacles to the continued rapid growth of clean energy, including renewables. Wind and solar produce energy intermittently and with seasonal variability. Traditionally, hydro dams with reservoirs and fossil fuel power plants have been used when variable energy production is low. Going forward, battery storage can be expanded, energy demand and supply can be matched, and long-distance transmission can smooth variability of renewable outputs. Bioenergy is often not carbon-neutral and may have negative consequences for food security. The growth of nuclear power is constrained by controversy around radioactive waste, nuclear weapon proliferation, and accidents. Hydropower growth is limited by the fact that the best sites have been developed, and new projects are confronting increased social and environmental concerns.
Low-carbon energy improves human health by minimizing climate change as well as reducing air pollution deaths, which were estimated at 7 million annually in 2016. Meeting the Paris Agreement goals that limit warming to a 2 °C increase could save about a million of those lives per year by 2050, whereas limiting global warming to 1.5 °C could save millions and simultaneously increase energy security and reduce poverty. Improving air quality also has economic benefits which may be larger than mitigation costs.
=== Energy conservation ===
Reducing energy demand is another major aspect of reducing emissions. If less energy is needed, there is more flexibility for clean energy development. It also makes it easier to manage the electricity grid, and minimizes carbon-intensive infrastructure development. Major increases in energy efficiency investment will be required to achieve climate goals, comparable to the level of investment in renewable energy. Several COVID-19 related changes in energy use patterns, energy efficiency investments, and funding have made forecasts for this decade more difficult and uncertain.
Strategies to reduce energy demand vary by sector. In the transport sector, passengers and freight can switch to more efficient travel modes, such as buses and trains, or use electric vehicles. Industrial strategies to reduce energy demand include improving heating systems and motors, designing less energy-intensive products, and increasing product lifetimes. In the building sector the focus is on better design of new buildings, and higher levels of energy efficiency in retrofitting. The use of technologies like heat pumps can also increase building energy efficiency.
=== Agriculture and industry ===
Agriculture and forestry face a triple challenge of limiting greenhouse gas emissions, preventing the further conversion of forests to agricultural land, and meeting increases in world food demand. A set of actions could reduce agriculture and forestry-based emissions by two-thirds from 2010 levels. These include reducing growth in demand for food and other agricultural products, increasing land productivity, protecting and restoring forests, and reducing greenhouse gas emissions from agricultural production.
On the demand side, a key component of reducing emissions is shifting people towards plant-based diets. Eliminating the production of livestock for meat and dairy would eliminate about 3/4ths of all emissions from agriculture and other land use. Livestock also occupy 37% of ice-free land area on Earth and consume feed from the 12% of land area used for crops, driving deforestation and land degradation.
Steel and cement production are responsible for about 13% of industrial CO2 emissions. In these industries, carbon-intensive materials such as coke and lime play an integral role in the production, so that reducing CO2 emissions requires research into alternative chemistries. Where energy production or CO2-intensive heavy industries continue to produce waste CO2, technology can sometimes be used to capture and store most of the gas instead of releasing it to the atmosphere. This technology, carbon capture and storage (CCS), could have a critical but limited role in reducing emissions. It is relatively expensive and has been deployed only to an extent that removes around 0.1% of annual greenhouse gas emissions.
=== Carbon dioxide removal ===
Natural carbon sinks can be enhanced to sequester significantly larger amounts of CO2 beyond naturally occurring levels. Reforestation and afforestation (planting forests where there were none before) are among the most mature sequestration techniques, although the latter raises food security concerns. Farmers can promote sequestration of carbon in soils through practices such as use of winter cover crops, reducing the intensity and frequency of tillage, and using compost and manure as soil amendments. Forest and landscape restoration yields many benefits for the climate, including greenhouse gas emissions sequestration and reduction. Restoration/recreation of coastal wetlands, prairie plots and seagrass meadows increases the uptake of carbon into organic matter. When carbon is sequestered in soils and in organic matter such as trees, there is a risk of the carbon being re-released into the atmosphere later through changes in land use, fire, or other changes in ecosystems.
The use of bioenergy in conjunction with carbon capture and storage (BECCS) can result in net negative emissions as CO2 is drawn from the atmosphere. It remains highly uncertain whether carbon dioxide removal techniques will be able to play a large role in limiting warming to 1.5 °C. Policy decisions that rely on carbon dioxide removal increase the risk of global warming rising beyond international goals.
== Adaptation ==
Adaptation is "the process of adjustment to current or expected changes in climate and its effects".: 5 Without additional mitigation, adaptation cannot avert the risk of "severe, widespread and irreversible" impacts. More severe climate change requires more transformative adaptation, which can be prohibitively expensive. The capacity and potential for humans to adapt is unevenly distributed across different regions and populations, and developing countries generally have less. The first two decades of the 21st century saw an increase in adaptive capacity in most low- and middle-income countries with improved access to basic sanitation and electricity, but progress is slow. Many countries have implemented adaptation policies. However, there is a considerable gap between necessary and available finance.
Adaptation to sea level rise consists of avoiding at-risk areas, learning to live with increased flooding, and building flood controls. If that fails, managed retreat may be needed. There are economic barriers for tackling dangerous heat impact. Avoiding strenuous work or having air conditioning is not possible for everybody. In agriculture, adaptation options include a switch to more sustainable diets, diversification, erosion control, and genetic improvements for increased tolerance to a changing climate. Insurance allows for risk-sharing, but is often difficult to get for people on lower incomes. Education, migration and early warning systems can reduce climate vulnerability. Planting mangroves or encouraging other coastal vegetation can buffer storms.
Ecosystems adapt to climate change, a process that can be supported by human intervention. By increasing connectivity between ecosystems, species can migrate to more favourable climate conditions. Species can also be introduced to areas acquiring a favourable climate. Protection and restoration of natural and semi-natural areas helps build resilience, making it easier for ecosystems to adapt. Many of the actions that promote adaptation in ecosystems, also help humans adapt via ecosystem-based adaptation. For instance, restoration of natural fire regimes makes catastrophic fires less likely, and reduces human exposure. Giving rivers more space allows for more water storage in the natural system, reducing flood risk. Restored forest acts as a carbon sink, but planting trees in unsuitable regions can exacerbate climate impacts.
There are synergies but also trade-offs between adaptation and mitigation. An example for synergy is increased food productivity, which has large benefits for both adaptation and mitigation. An example of a trade-off is that increased use of air conditioning allows people to better cope with heat, but increases energy demand. Another trade-off example is that more compact urban development may reduce emissions from transport and construction, but may also increase the urban heat island effect, exposing people to heat-related health risks.
== Policies and politics ==
Countries that are most vulnerable to climate change have typically been responsible for a small share of global emissions. This raises questions about justice and fairness. Limiting global warming makes it much easier to achieve the UN's Sustainable Development Goals, such as eradicating poverty and reducing inequalities. The connection is recognized in Sustainable Development Goal 13 which is to "take urgent action to combat climate change and its impacts". The goals on food, clean water and ecosystem protection have synergies with climate mitigation.
The geopolitics of climate change is complex. It has often been framed as a free-rider problem, in which all countries benefit from mitigation done by other countries, but individual countries would lose from switching to a low-carbon economy themselves. Sometimes mitigation also has localized benefits though. For instance, the benefits of a coal phase-out to public health and local environments exceed the costs in almost all regions. Furthermore, net importers of fossil fuels win economically from switching to clean energy, causing net exporters to face stranded assets: fossil fuels they cannot sell.
=== Policy options ===
A wide range of policies, regulations, and laws are being used to reduce emissions. As of 2019, carbon pricing covers about 20% of global greenhouse gas emissions. Carbon can be priced with carbon taxes and emissions trading systems. Direct global fossil fuel subsidies reached $319 billion in 2017, and $5.2 trillion when indirect costs such as air pollution are priced in. Ending these can cause a 28% reduction in global carbon emissions and a 46% reduction in air pollution deaths. Money saved on fossil subsidies could be used to support the transition to clean energy instead. More direct methods to reduce greenhouse gases include vehicle efficiency standards, renewable fuel standards, and air pollution regulations on heavy industry. Several countries require utilities to increase the share of renewables in power production.
==== Climate justice ====
Policy designed through the lens of climate justice tries to address human rights issues and social inequality. According to proponents of climate justice, the costs of climate adaptation should be paid by those most responsible for climate change, while the beneficiaries of payments should be those suffering impacts. One way this can be addressed in practice is to have wealthy nations pay poorer countries to adapt.
Oxfam found that in 2023 the wealthiest 10% of people were responsible for 50% of global emissions, while the bottom 50% were responsible for just 8%. Production of emissions is another way to look at responsibility: under that approach, the top 21 fossil fuel companies would owe cumulative climate reparations of $5.4 trillion over the period 2025–2050. To achieve a just transition, people working in the fossil fuel sector would also need other jobs, and their communities would need investments.
=== International climate agreements ===
Nearly all countries in the world are parties to the 1994 United Nations Framework Convention on Climate Change (UNFCCC). The goal of the UNFCCC is to prevent dangerous human interference with the climate system. As stated in the convention, this requires that greenhouse gas concentrations are stabilized in the atmosphere at a level where ecosystems can adapt naturally to climate change, food production is not threatened, and economic development can be sustained. The UNFCCC does not itself restrict emissions but rather provides a framework for protocols that do. Global emissions have risen since the UNFCCC was signed. Its yearly conferences are the stage of global negotiations.
The 1997 Kyoto Protocol extended the UNFCCC and included legally binding commitments for most developed countries to limit their emissions. During the negotiations, the G77 (representing developing countries) pushed for a mandate requiring developed countries to "[take] the lead" in reducing their emissions, since developed countries contributed most to the accumulation of greenhouse gases in the atmosphere. Per-capita emissions were also still relatively low in developing countries and developing countries would need to emit more to meet their development needs.
The 2009 Copenhagen Accord has been widely portrayed as disappointing because of its low goals, and was rejected by poorer nations including the G77. Associated parties aimed to limit the global temperature rise to below 2 °C. The Accord set the goal of sending $100 billion per year to developing countries for mitigation and adaptation by 2020, and proposed the founding of the Green Climate Fund. As of 2020, only 83.3 billion were delivered. Only in 2023 the target is expected to be achieved.
In 2015 all UN countries negotiated the Paris Agreement, which aims to keep global warming well below 2.0 °C and contains an aspirational goal of keeping warming under 1.5 °C. The agreement replaced the Kyoto Protocol. Unlike Kyoto, no binding emission targets were set in the Paris Agreement. Instead, a set of procedures was made binding. Countries have to regularly set ever more ambitious goals and reevaluate these goals every five years. The Paris Agreement restated that developing countries must be financially supported. As of March 2025, 194 states and the European Union have acceded to or ratified the agreement.
The 1987 Montreal Protocol, an international agreement to phase out production of ozone-depleting gases, has had benefits for climate change mitigation. Several ozone-depleting gases like chlorofluorocarbons are powerful greenhouse gases, so banning their production and usage may have avoided a temperature rise of 0.5 °C–1.0 °C, as well as additional warming by preventing damage to vegetation from ultraviolet radiation. It is estimated that the agreement has been more effective at curbing greenhouse gas emissions than the Kyoto Protocol specifically designed to do so. The most recent amendment to the Montreal Protocol, the 2016 Kigali Amendment, committed to reducing the emissions of hydrofluorocarbons, which served as a replacement for banned ozone-depleting gases and are also potent greenhouse gases. Should countries comply with the amendment, a warming of 0.3 °C–0.5 °C is estimated to be avoided.
=== National responses ===
In 2019, the United Kingdom parliament became the first national government to declare a climate emergency. Other countries and jurisdictions followed suit. That same year, the European Parliament declared a "climate and environmental emergency". The European Commission presented its European Green Deal with the goal of making the EU carbon-neutral by 2050. In 2021, the European Commission released its "Fit for 55" legislation package, which contains guidelines for the car industry; all new cars on the European market must be zero-emission vehicles from 2035.
Major countries in Asia have made similar pledges: South Korea and Japan have committed to become carbon-neutral by 2050, and China by 2060. While India has strong incentives for renewables, it also plans a significant expansion of coal in the country. Vietnam is among very few coal-dependent, fast-developing countries that pledged to phase out unabated coal power by the 2040s or as soon as possible thereafter.
As of 2021, based on information from 48 national climate plans, which represent 40% of the parties to the Paris Agreement, estimated total greenhouse gas emissions will be 0.5% lower compared to 2010 levels, below the 45% or 25% reduction goals to limit global warming to 1.5 °C or 2 °C, respectively.
== Society ==
=== Denial and misinformation ===
Public debate about climate change has been strongly affected by climate change denial and misinformation, which originated in the United States and has since spread to other countries, particularly Canada and Australia. Climate change denial has originated from fossil fuel companies, industry groups, conservative think tanks, and contrarian scientists. Like the tobacco industry, the main strategy of these groups has been to manufacture doubt about climate-change related scientific data and results. People who hold unwarranted doubt about climate change are called climate change "skeptics", although "contrarians" or "deniers" are more appropriate terms.
There are different variants of climate denial: some deny that warming takes place at all, some acknowledge warming but attribute it to natural influences, and some minimize the negative impacts of climate change. Manufacturing uncertainty about the science later developed into a manufactured controversy: creating the belief that there is significant uncertainty about climate change within the scientific community to delay policy changes. Strategies to promote these ideas include criticism of scientific institutions, and questioning the motives of individual scientists. An echo chamber of climate-denying blogs and media has further fomented misunderstanding of climate change.
=== Public awareness and opinion ===
Climate change came to international public attention in the late 1980s. Due to media coverage in the early 1990s, people often confused climate change with other environmental issues like ozone depletion. In popular culture, the climate fiction movie The Day After Tomorrow (2004) and the Al Gore documentary An Inconvenient Truth (2006) focused on climate change.
Significant regional, gender, age and political differences exist in both public concern for, and understanding of, climate change. More highly educated people, and in some countries, women and younger people, were more likely to see climate change as a serious threat. College biology textbooks from the 2010s featured less content on climate change compared to those from the preceding decade, with decreasing emphasis on solutions. Partisan gaps also exist in many countries, and countries with high CO2 emissions tend to be less concerned. Views on causes of climate change vary widely between countries. Media coverage linked to protests has had impacts on public sentiment as well as on which aspects of climate change are focused upon. Higher levels of worry are associated with stronger public support for policies that address climate change. Concern has increased over time, and in 2021 a majority of citizens in 30 countries expressed a high level of worry about climate change, or view it as a global emergency. A 2024 survey across 125 countries found that 89% of the global population demanded intensified political action, but systematically underestimated other peoples' willingness to act.
==== Climate movement ====
Climate protests demand that political leaders take action to prevent climate change. They can take the form of public demonstrations, fossil fuel divestment, lawsuits and other activities. Prominent demonstrations include the School Strike for Climate. In this initiative, young people across the globe have been protesting since 2018 by skipping school on Fridays, inspired by Swedish activist and then-teenager Greta Thunberg. Mass civil disobedience actions by groups like Extinction Rebellion have protested by disrupting roads and public transport.
Litigation is increasingly used as a tool to strengthen climate action from public institutions and companies. Activists also initiate lawsuits which target governments and demand that they take ambitious action or enforce existing laws on climate change. Lawsuits against fossil-fuel companies generally seek compensation for loss and damage.
== History ==
=== Early discoveries ===
Scientists in the 19th century such as Alexander von Humboldt began to foresee the effects of climate change. In the 1820s, Joseph Fourier proposed the greenhouse effect to explain why Earth's temperature was higher than the Sun's energy alone could explain. Earth's atmosphere is transparent to sunlight, so sunlight reaches the surface where it is converted to heat. However, the atmosphere is not transparent to heat radiating from the surface, and captures some of that heat, which in turn warms the planet.
In 1856 Eunice Newton Foote demonstrated that the warming effect of the Sun is greater for air with water vapour than for dry air, and that the effect is even greater with carbon dioxide (CO2). She concluded that "An atmosphere of that gas would give to our earth a high temperature..."
Starting in 1859, John Tyndall established that nitrogen and oxygen—together totalling 99% of dry air—are transparent to radiated heat. However, water vapour and gases such as methane and carbon dioxide absorb radiated heat and re-radiate that heat into the atmosphere. Tyndall proposed that changes in the concentrations of these gases may have caused climatic changes in the past, including ice ages.
Svante Arrhenius noted that water vapour in air continuously varied, but the CO2 concentration in air was influenced by long-term geological processes. Warming from increased CO2 levels would increase the amount of water vapour, amplifying warming in a positive feedback loop. In 1896, he published the first climate model of its kind, projecting that halving CO2 levels could have produced a drop in temperature initiating an ice age. Arrhenius calculated the temperature increase expected from doubling CO2 to be around 5–6 °C. Other scientists were initially sceptical and believed that the greenhouse effect was saturated so that adding more CO2 would make no difference, and that the climate would be self-regulating. Beginning in 1938, Guy Stewart Callendar published evidence that climate was warming and CO2 levels were rising, but his calculations met the same objections.
=== Development of a scientific consensus ===
In the 1950s, Gilbert Plass created a detailed computer model that included different atmospheric layers and the infrared spectrum. This model predicted that increasing CO2 levels would cause warming. Around the same time, Hans Suess found evidence that CO2 levels had been rising, and Roger Revelle showed that the oceans would not absorb the increase. The two scientists subsequently helped Charles Keeling to begin a record of continued increase—the "Keeling Curve"—which was part of continued scientific investigation through the 1960s into possible human causation of global warming. Studies such as the National Research Council's 1979 Charney Report supported the accuracy of climate models that forecast significant warming. Human causation of observed global warming and dangers of unmitigated warming were publicly presented in James Hansen's 1988 testimony before a US Senate committee. The Intergovernmental Panel on Climate Change (IPCC), set up in 1988 to provide formal advice to the world's governments, spurred interdisciplinary research. As part of the IPCC reports, scientists assess the scientific discussion that takes place in peer-reviewed journal articles.
There is a near-complete scientific consensus that the climate is warming and that this is caused by human activities. As of 2019, agreement in recent literature reached over 99%. No scientific body of national or international standing disagrees with this view. Consensus has further developed that some form of action should be taken to protect people against the impacts of climate change. National science academies have called on world leaders to cut global emissions. The 2021 IPCC Assessment Report stated that it is "unequivocal" that climate change is caused by humans.
== References ==
=== Sources ===
This article incorporates text from a free content work. Licensed under CC BY-SA 3.0. Text taken from The status of women in agrifood systems – Overview, FAO, FAO.
==== IPCC reports ====
==== Other peer-reviewed sources ====
==== Books, reports and legal documents ====
==== Non-technical sources ====
== External links ==
Intergovernmental Panel on Climate Change: IPCC (IPCC)
UN: Climate Change (UN)
Met Office: Climate Guide (Met Office)
National Oceanic and Atmospheric Administration: Climate (NOAA) | Wikipedia/Climate_change_theory |
In the physics of electromagnetism, the Abraham–Lorentz force (also known as the Lorentz–Abraham force) is the reaction force on an accelerating charged particle caused by the particle emitting electromagnetic radiation by self-interaction. It is also called the radiation reaction force, the radiation damping force, or the self-force. It is named after the physicists Max Abraham and Hendrik Lorentz.
The formula, although predating the theory of special relativity, was initially calculated for non-relativistic velocity approximations. It was extended to arbitrary velocities by Max Abraham and was shown to be physically consistent by George Adolphus Schott. The non-relativistic form is called Lorentz self-force while the relativistic version is called the Lorentz–Dirac force or collectively known as Abraham–Lorentz–Dirac force. The equations are in the domain of classical physics, not quantum physics, and therefore may not be valid at distances of roughly the Compton wavelength or below. There are, however, two analogs of the formula that are both fully quantum and relativistic: one is called the "Abraham–Lorentz–Dirac–Langevin equation", the other is the self-force on a moving mirror.
The force is proportional to the square of the object's charge, multiplied by the jerk that it is experiencing. (Jerk is the rate of change of acceleration.) The force points in the direction of the jerk. For example, in a cyclotron, where the jerk points opposite to the velocity, the radiation reaction is directed opposite to the velocity of the particle, providing a braking action. The Abraham–Lorentz force is the source of the radiation resistance of a radio antenna radiating radio waves.
There are pathological solutions of the Abraham–Lorentz–Dirac equation in which a particle accelerates in advance of the application of a force, so-called pre-acceleration solutions. Since this would represent an effect occurring before its cause (retrocausality), some theories have speculated that the equation allows signals to travel backward in time, thus challenging the physical principle of causality. One resolution of this problem was discussed by Arthur D. Yaghjian and was further discussed by Fritz Rohrlich and Rodrigo Medina. Furthermore, some authors argue that a radiation reaction force is unnecessary, introducing a corresponding stress-energy tensor that naturally conserves energy and momentum in Minkowski space and other suitable spacetimes.
== Definition and description ==
The Lorentz self-force derived for non-relativistic velocity approximation
v
≪
c
{\displaystyle v\ll c}
, is given in SI units by:
F
r
a
d
=
μ
0
q
2
6
π
c
a
˙
=
q
2
6
π
ε
0
c
3
a
˙
=
2
3
q
2
4
π
ε
0
c
3
a
˙
{\displaystyle \mathbf {F} _{\mathrm {rad} }={\frac {\mu _{0}q^{2}}{6\pi c}}\mathbf {\dot {a}} ={\frac {q^{2}}{6\pi \varepsilon _{0}c^{3}}}\mathbf {\dot {a}} ={\frac {2}{3}}{\frac {q^{2}}{4\pi \varepsilon _{0}c^{3}}}\mathbf {\dot {a}} }
or in Gaussian units by
F
r
a
d
=
2
3
q
2
c
3
a
˙
.
{\displaystyle \mathbf {F} _{\mathrm {rad} }={2 \over 3}{\frac {q^{2}}{c^{3}}}\mathbf {\dot {a}} .}
where
F
r
a
d
{\displaystyle \mathbf {F} _{\mathrm {rad} }}
is the force,
a
˙
{\displaystyle \mathbf {\dot {a}} }
is the derivative of acceleration, or the third derivative of displacement, also called jerk, μ0 is the magnetic constant, ε0 is the electric constant, c is the speed of light in free space, and q is the electric charge of the particle.
Physically, an accelerating charge emits radiation (according to the Larmor formula), which carries momentum away from the charge. Since momentum is conserved, the charge is pushed in the direction opposite the direction of the emitted radiation. In fact the formula above for radiation force can be derived from the Larmor formula, as shown below.
The Abraham–Lorentz force, a generalization of Lorentz self-force for arbitrary velocities is given by:
F
r
a
d
=
μ
0
q
2
6
π
c
(
γ
2
a
˙
+
γ
4
v
(
v
⋅
a
˙
)
c
2
+
3
γ
4
a
(
v
⋅
a
)
c
2
+
3
γ
6
v
(
v
⋅
a
)
2
c
4
)
{\displaystyle \mathbf {F} _{\mathrm {rad} }={\frac {\mu _{0}q^{2}}{6\pi c}}\left(\gamma ^{2}{\dot {a}}+{\frac {\gamma ^{4}v(v\cdot {\dot {a}})}{c^{2}}}+{\frac {3\gamma ^{4}a(v\cdot a)}{c^{2}}}+{\frac {3\gamma ^{6}v(v\cdot a)^{2}}{c^{4}}}\right)}
Where
γ
{\displaystyle \gamma }
is the Lorentz factor associated with
v
{\displaystyle v}
, the velocity of particle. The formula is consistent with special relativity and reduces to Lorentz's self-force expression for low velocity limit.
The covariant form of radiation reaction deduced by Dirac for arbitrary shape of elementary charges is found to be:
F
μ
r
a
d
=
μ
0
q
2
6
π
m
c
[
d
2
p
μ
d
τ
2
−
p
μ
m
2
c
2
(
d
p
ν
d
τ
d
p
ν
d
τ
)
]
{\displaystyle F_{\mu }^{\mathrm {rad} }={\frac {\mu _{0}q^{2}}{6\pi mc}}\left[{\frac {d^{2}p_{\mu }}{d\tau ^{2}}}-{\frac {p_{\mu }}{m^{2}c^{2}}}\left({\frac {dp_{\nu }}{d\tau }}{\frac {dp^{\nu }}{d\tau }}\right)\right]}
== History ==
The first calculation of electromagnetic radiation energy due to current was given by George Francis FitzGerald in 1883, in which radiation resistance appears. However, dipole antenna experiments by Heinrich Hertz made a bigger impact and gathered commentary by Poincaré on the amortissement or damping of the oscillator due to the emission of radiation. Qualitative discussions surrounding damping effects of radiation emitted by accelerating charges was sparked by Henry Poincaré in 1891. In 1892, Hendrik Lorentz derived the self-interaction force of charges for low velocities but did not relate it to radiation losses. Suggestion of a relationship between radiation energy loss and self-force was first made by Max Planck. Planck's concept of the damping force, which did not assume any particular shape for elementary charged particles, was applied by Max Abraham to find the radiation resistance of an antenna in 1898, which remains the most practical application of the phenomenon.
In the early 1900s, Abraham formulated a generalization of the Lorentz self-force to arbitrary velocities, the physical consistency of which was later shown by George Adolphus Schott. Schott was able to derive the Abraham equation and attributed "acceleration energy" to be the source of energy of the electromagnetic radiation. Originally submitted as an essay for the 1908 Adams Prize, he won the competition and had the essay published as a book in 1912. The relationship between self-force and radiation reaction became well-established at this point. Wolfgang Pauli first obtained the covariant form of the radiation reaction and in 1938, Paul Dirac found that the equation of motion of charged particles, without assuming the shape of the particle, contained Abraham's formula within reasonable approximations. The equations derived by Dirac are considered exact within the limits of classical theory.
== Background ==
In classical electrodynamics, problems are typically divided into two classes:
Problems in which the charge and current sources of fields are specified and the fields are calculated, and
The reverse situation, problems in which the fields are specified and the motion of particles are calculated.
In some fields of physics, such as plasma physics and the calculation of transport coefficients (conductivity, diffusivity, etc.), the fields generated by the sources and the motion of the sources are solved self-consistently. In such cases, however, the motion of a selected source is calculated in response to fields generated by all other sources. Rarely is the motion of a particle (source) due to the fields generated by that same particle calculated. The reason for this is twofold:
Neglect of the "self-fields" usually leads to answers that are accurate enough for many applications, and
Inclusion of self-fields leads to problems in physics such as renormalization, some of which are still unsolved, that relate to the very nature of matter and energy.
These conceptual problems created by self-fields are highlighted in a standard graduate text. [Jackson]
The difficulties presented by this problem touch one of the most fundamental aspects of physics, the nature of the elementary particle. Although partial solutions, workable within limited areas, can be given, the basic problem remains unsolved. One might hope that the transition from classical to quantum-mechanical treatments would remove the difficulties. While there is still hope that this may eventually occur, the present quantum-mechanical discussions are beset with even more elaborate troubles than the classical ones. It is one of the triumphs of comparatively recent years (~ 1948–1950) that the concepts of Lorentz covariance and gauge invariance were exploited sufficiently cleverly to circumvent these difficulties in quantum electrodynamics and so allow the calculation of very small radiative effects to extremely high precision, in full agreement with experiment. From a fundamental point of view, however, the difficulties remain.
The Abraham–Lorentz force is the result of the most fundamental calculation of the effect of self-generated fields. It arises from the observation that accelerating charges emit radiation. The Abraham–Lorentz force is the average force that an accelerating charged particle feels in the recoil from the emission of radiation. The introduction of quantum effects leads one to quantum electrodynamics. The self-fields in quantum electrodynamics generate a finite number of infinities in the calculations that can be removed by the process of renormalization. This has led to a theory that is able to make the most accurate predictions that humans have made to date. (See precision tests of QED.) The renormalization process fails, however, when applied to the gravitational force. The infinities in that case are infinite in number, which causes the failure of renormalization. Therefore, general relativity has an unsolved self-field problem. String theory and loop quantum gravity are current attempts to resolve this problem, formally called the problem of radiation reaction or the problem of self-force.
== Derivation ==
The simplest derivation for the self-force is found for periodic motion from the Larmor formula for the power radiated from a point charge that moves with velocity much lower than that of speed of light:
P
=
μ
0
q
2
6
π
c
a
2
.
{\displaystyle P={\frac {\mu _{0}q^{2}}{6\pi c}}\mathbf {a} ^{2}.}
If we assume the motion of a charged particle is periodic, then the average work done on the particle by the Abraham–Lorentz force is the negative of the Larmor power integrated over one period from
τ
1
{\displaystyle \tau _{1}}
to
τ
2
{\displaystyle \tau _{2}}
:
∫
τ
1
τ
2
F
r
a
d
⋅
v
d
t
=
∫
τ
1
τ
2
−
P
d
t
=
−
∫
τ
1
τ
2
μ
0
q
2
6
π
c
a
2
d
t
=
−
∫
τ
1
τ
2
μ
0
q
2
6
π
c
d
v
d
t
⋅
d
v
d
t
d
t
.
{\displaystyle \int _{\tau _{1}}^{\tau _{2}}\mathbf {F} _{\mathrm {rad} }\cdot \mathbf {v} dt=\int _{\tau _{1}}^{\tau _{2}}-Pdt=-\int _{\tau _{1}}^{\tau _{2}}{\frac {\mu _{0}q^{2}}{6\pi c}}\mathbf {a} ^{2}dt=-\int _{\tau _{1}}^{\tau _{2}}{\frac {\mu _{0}q^{2}}{6\pi c}}{\frac {d\mathbf {v} }{dt}}\cdot {\frac {d\mathbf {v} }{dt}}dt.}
The above expression can be integrated by parts. If we assume that there is periodic motion, the boundary term in the integral by parts disappears:
∫
τ
1
τ
2
F
r
a
d
⋅
v
d
t
=
−
μ
0
q
2
6
π
c
d
v
d
t
⋅
v
|
τ
1
τ
2
+
∫
τ
1
τ
2
μ
0
q
2
6
π
c
d
2
v
d
t
2
⋅
v
d
t
=
−
0
+
∫
τ
1
τ
2
μ
0
q
2
6
π
c
a
˙
⋅
v
d
t
.
{\displaystyle \int _{\tau _{1}}^{\tau _{2}}\mathbf {F} _{\mathrm {rad} }\cdot \mathbf {v} dt=-{\frac {\mu _{0}q^{2}}{6\pi c}}{\frac {d\mathbf {v} }{dt}}\cdot \mathbf {v} {\bigg |}_{\tau _{1}}^{\tau _{2}}+\int _{\tau _{1}}^{\tau _{2}}{\frac {\mu _{0}q^{2}}{6\pi c}}{\frac {d^{2}\mathbf {v} }{dt^{2}}}\cdot \mathbf {v} dt=-0+\int _{\tau _{1}}^{\tau _{2}}{\frac {\mu _{0}q^{2}}{6\pi c}}\mathbf {\dot {a}} \cdot \mathbf {v} dt.}
Clearly, we can identify the Lorentz self-force equation which is applicable to slow moving particles as:
F
r
a
d
=
μ
0
q
2
6
π
c
a
˙
.
{\displaystyle \mathbf {F} _{\mathrm {rad} }={\frac {\mu _{0}q^{2}}{6\pi c}}\mathbf {{\dot {a}}.} }
A more rigorous derivation, which does not require periodic motion, was found using an effective field theory formulation.
A generalized equation for arbitrary velocities was formulated by Max Abraham, which is found to be consistent with special relativity. An alternative derivation, making use of theory of relativity which was well established at that time, was found by Dirac without any assumption of the shape of the charged particle.
== Signals from the future ==
Below is an illustration of how a classical analysis can lead to surprising results. The classical theory can be seen to challenge standard pictures of causality, thus signaling either a breakdown or a need for extension of the theory. In this case the extension is to quantum mechanics and its relativistic counterpart quantum field theory. See the quote from Rohrlich in the introduction concerning "the importance of obeying the validity limits of a physical theory".
For a particle in an external force
F
e
x
t
{\displaystyle \mathbf {F} _{\mathrm {ext} }}
, we have
m
v
˙
=
F
r
a
d
+
F
e
x
t
=
m
t
0
v
¨
+
F
e
x
t
.
{\displaystyle m{\dot {\mathbf {v} }}=\mathbf {F} _{\mathrm {rad} }+\mathbf {F} _{\mathrm {ext} }=mt_{0}{\ddot {\mathbf {v} }}+\mathbf {F} _{\mathrm {ext} }.}
where
t
0
=
μ
0
q
2
6
π
m
c
.
{\displaystyle t_{0}={\frac {\mu _{0}q^{2}}{6\pi mc}}.}
This equation can be integrated once to obtain
m
v
˙
=
1
t
0
∫
t
∞
exp
(
−
t
′
−
t
t
0
)
F
e
x
t
(
t
′
)
d
t
′
.
{\displaystyle m{\dot {\mathbf {v} }}={1 \over t_{0}}\int _{t}^{\infty }\exp \left(-{t'-t \over t_{0}}\right)\,\mathbf {F} _{\mathrm {ext} }(t')\,dt'.}
The integral extends from the present to infinitely far in the future. Thus future values of the force affect the acceleration of the particle in the present. The future values are weighted by the factor
exp
(
−
t
′
−
t
t
0
)
{\displaystyle \exp \left(-{t'-t \over t_{0}}\right)}
which falls off rapidly for times greater than
t
0
{\displaystyle t_{0}}
in the future. Therefore, signals from an interval approximately
t
0
{\displaystyle t_{0}}
into the future affect the acceleration in the present. For an electron, this time is approximately
10
−
24
{\displaystyle 10^{-24}}
sec, which is the time it takes for a light wave to travel across the "size" of an electron, the classical electron radius. One way to define this "size" is as follows: it is (up to some constant factor) the distance
r
{\displaystyle r}
such that two electrons placed at rest at a distance
r
{\displaystyle r}
apart and allowed to fly apart, would have sufficient energy to reach half the speed of light. In other words, it forms the length (or time, or energy) scale where something as light as an electron would be fully relativistic. It is worth noting that this expression does not involve the Planck constant at all, so although it indicates something is wrong at this length scale, it does not directly relate to quantum uncertainty, or to the frequency–energy relation of a photon. Although it is common in quantum mechanics to treat
ℏ
→
0
{\displaystyle \hbar \to 0}
as a "classical limit", some speculate that even the classical theory needs renormalization, no matter how the Planck constant would be fixed.
== Abraham–Lorentz–Dirac force ==
To find the relativistic generalization, Dirac renormalized the mass in the equation of motion with the Abraham–Lorentz force in 1938. This renormalized equation of motion is called the Abraham–Lorentz–Dirac equation of motion.
=== Definition ===
The expression derived by Dirac is given in signature (− + + +) by
F
μ
r
a
d
=
μ
0
q
2
6
π
m
c
[
d
2
p
μ
d
τ
2
−
p
μ
m
2
c
2
(
d
p
ν
d
τ
d
p
ν
d
τ
)
]
.
{\displaystyle F_{\mu }^{\mathrm {rad} }={\frac {\mu _{0}q^{2}}{6\pi mc}}\left[{\frac {d^{2}p_{\mu }}{d\tau ^{2}}}-{\frac {p_{\mu }}{m^{2}c^{2}}}\left({\frac {dp_{\nu }}{d\tau }}{\frac {dp^{\nu }}{d\tau }}\right)\right].}
With Liénard's relativistic generalization of Larmor's formula in the co-moving frame,
P
=
μ
0
q
2
a
2
γ
6
6
π
c
,
{\displaystyle P={\frac {\mu _{0}q^{2}a^{2}\gamma ^{6}}{6\pi c}},}
one can show this to be a valid force by manipulating the time average equation for power:
1
Δ
t
∫
0
t
P
d
t
=
1
Δ
t
∫
0
t
F
⋅
v
d
t
.
{\displaystyle {\frac {1}{\Delta t}}\int _{0}^{t}Pdt={\frac {1}{\Delta t}}\int _{0}^{t}{\textbf {F}}\cdot {\textbf {v}}\,dt.}
== Paradoxes ==
=== Pre-acceleration ===
Similar to the non-relativistic case, there are pathological solutions using the Abraham–Lorentz–Dirac equation that anticipate a change in the external force and according to which the particle accelerates in advance of the application of a force, so-called preacceleration solutions. One resolution of this problem was discussed by Yaghjian, and is further discussed by Rohrlich and Medina.
=== Runaway solutions ===
Runaway solutions are solutions to ALD equations that suggest the force on objects will increase exponential over time. It is considered as an unphysical solution.
=== Hyperbolic motion ===
The ALD equations are known to be zero for constant acceleration or hyperbolic motion in Minkowski spacetime diagram. The subject of whether in such condition electromagnetic radiation exists was matter of debate until Fritz Rohrlich resolved the problem by showing that hyperbolically moving charges do emit radiation. Subsequently, the issue is discussed in context of energy conservation and equivalence principle which is classically resolved by considering "acceleration energy" or Schott energy.
== Self-interactions ==
However the antidamping mechanism resulting from the Abraham–Lorentz force can be compensated by other nonlinear terms, which are frequently disregarded in the expansions of the retarded Liénard–Wiechert potential.
== Landau–Lifshitz radiation damping force ==
The Abraham–Lorentz–Dirac force leads to some pathological solutions. In order to avoid this, Lev Landau and Evgeny Lifshitz came with the following formula for radiation damping force, which is valid when the radiation damping force is small compared with the Lorentz force in some frame of reference (assuming it exists),
g
i
=
2
e
3
3
m
c
3
{
∂
F
i
k
∂
x
l
u
k
u
l
−
e
m
c
2
[
F
i
l
F
k
l
u
k
−
(
F
k
l
u
l
)
(
F
k
m
u
m
)
u
i
]
}
{\displaystyle g^{i}={\frac {2e^{3}}{3mc^{3}}}\left\{{\frac {\partial F^{ik}}{\partial x^{l}}}u_{k}u^{l}-{\frac {e}{mc^{2}}}\left[F^{il}F_{kl}u^{k}-(F_{kl}u^{l})(F^{km}u_{m})u^{i}\right]\right\}}
so that the equation of motion of the charge
e
{\displaystyle e}
in an external field
F
i
k
{\displaystyle F^{ik}}
can be written as
m
c
d
u
i
d
s
=
e
c
F
i
k
u
k
+
g
i
.
{\displaystyle mc{\frac {du^{i}}{ds}}={\frac {e}{c}}F^{ik}u_{k}+g^{i}.}
Here
u
i
=
(
γ
,
γ
v
/
c
)
{\displaystyle u^{i}=(\gamma ,\gamma \mathbf {v} /c)}
is the four-velocity of the particle,
γ
=
1
/
1
−
v
2
/
c
2
{\displaystyle \gamma =1/{\sqrt {1-v^{2}/c^{2}}}}
is the Lorentz factor and
v
{\displaystyle \mathbf {v} }
is the three-dimensional velocity vector. The three-dimensional Landau–Lifshitz radiation damping force can be written as
F
r
a
d
=
2
e
3
γ
3
m
c
3
{
D
E
D
t
+
1
c
v
×
D
H
D
t
}
+
2
e
4
3
m
2
c
4
[
E
×
H
+
1
c
H
×
(
H
×
v
)
+
1
c
E
(
v
⋅
E
)
]
−
2
e
4
γ
2
v
3
m
2
c
5
[
(
E
+
1
c
v
×
H
)
2
−
1
c
2
(
E
⋅
v
)
2
]
{\displaystyle \mathbf {F} _{\mathrm {rad} }={\frac {2e^{3}\gamma }{3mc^{3}}}\left\{{\frac {D\mathbf {E} }{Dt}}+{\frac {1}{c}}\mathbf {v} \times {\frac {D\mathbf {H} }{Dt}}\right\}+{\frac {2e^{4}}{3m^{2}c^{4}}}\left[\mathbf {E} \times \mathbf {H} +{\frac {1}{c}}\mathbf {H} \times (\mathbf {H} \times \mathbf {v} )+{\frac {1}{c}}\mathbf {E} (\mathbf {v} \cdot \mathbf {E} )\right]-{\frac {2e^{4}\gamma ^{2}\mathbf {v} }{3m^{2}c^{5}}}\left[\left(\mathbf {E} +{\frac {1}{c}}\mathbf {v} \times \mathbf {H} \right)^{2}-{\frac {1}{c^{2}}}(\mathbf {E} \cdot \mathbf {v} )^{2}\right]}
where
D
/
D
t
=
∂
/
∂
t
+
v
⋅
∇
{\displaystyle D/Dt=\partial /\partial t+\mathbf {v} \cdot \nabla }
is the total derivative.
== Experimental observations ==
While the Abraham–Lorentz force is largely neglected for many experimental considerations, it gains importance for plasmonic excitations in larger nanoparticles due to large local field enhancements. Radiation damping acts as a limiting factor for the plasmonic excitations in surface-enhanced Raman scattering. The damping force was shown to broaden surface plasmon resonances in gold nanoparticles, nanorods and clusters.
The effects of radiation damping on nuclear magnetic resonance were also observed by Nicolaas Bloembergen and Robert Pound, who reported its dominance over spin–spin and spin–lattice relaxation mechanisms for certain cases.
The Abraham–Lorentz force has been observed in the semiclassical regime in experiments which involve the scattering of a relativistic beam of electrons with a high intensity laser. In the experiments, a supersonic jet of helium gas is intercepted by a high-intensity (1018–1020 W/cm2) laser. The laser ionizes the helium gas and accelerates the electrons via what is known as the “laser-wakefield” effect. A second high-intensity laser beam is then propagated counter to this accelerated electron beam. In a small number of cases, inverse-Compton scattering occurs between the photons and the electron beam, and the spectra of the scattered electrons and photons are measured. The photon spectra are then compared with spectra calculated from Monte Carlo simulations that use either the QED or classical LL equations of motion.
== Collective effects ==
The effects of radiation reaction are often considered within the framework of single-particle dynamics. However, interesting phenomena arise when a collection of charged particles is subjected to strong electromagnetic fields, such as in a plasma. In such scenarios, the collective behavior of the plasma can significantly modify its properties due to radiation reaction effects.
Theoretical studies have shown that in environments with strong magnetic fields, like those found around pulsars and magnetars, radiation reaction cooling can alter the collective dynamics of the plasma. This modification can lead to instabilities within the plasma. Specifically, in the high magnetic fields typical of these astrophysical objects, the momentum distribution of particles is bunched and becomes anisotropic due to radiation reaction forces, potentially driving plasma instabilities and affecting overall plasma behavior. Among these instabilities, the firehose instability can arise due to the anisotropic pressure, and electron cyclotron maser due to population inversion in the rings.
== See also ==
Lorentz force
Cyclotron radiation
Synchrotron radiation
Electromagnetic mass
Radiation resistance
Radiation damping
Wheeler–Feynman absorber theory
Magnetic radiation reaction force
== References ==
== Further reading ==
Griffiths, David J. (1998). Introduction to Electrodynamics (3rd ed.). Prentice Hall. ISBN 978-0-13-805326-0. See sections 11.2.2 and 11.2.3
Jackson, John D. (1998). Classical Electrodynamics (3rd ed.). Wiley. ISBN 978-0-471-30932-1.
Donald H. Menzel (1960) Fundamental Formulas of Physics, Dover Publications Inc., ISBN 0-486-60595-7, vol. 1, p. 345.
Stephen Parrott (1987) Relativistic Electrodynamics and Differential Geometry, § 4.3 Radiation reaction and the Lorentz–Dirac equation, pages 136–45, and § 5.5 Peculiar solutions of the Lorentz–Dirac equation, pp. 195–204, Springer-Verlag ISBN 0-387-96435-5 .
== External links ==
MathPages – Does A Uniformly Accelerating Charge Radiate?
Feynman: The Development of the Space-Time View of Quantum Electrodynamics
EC. del Río: Radiation of an accelerated charge | Wikipedia/Radiation_reaction_force |
A prediction (Latin præ-, "before," and dictum, "something said") or forecast is a statement about a future event or about future data. Predictions are often, but not always, based upon experience or knowledge of forecasters. There is no universal agreement about the exact difference between "prediction" and "estimation"; different authors and disciplines ascribe different connotations.
Future events are necessarily uncertain, so guaranteed accurate information about the future is impossible. Prediction can be useful to assist in making plans about possible developments.
== Opinion ==
In a non-statistical sense, the term "prediction" is often used to refer to an informed guess or opinion.
A prediction of this kind might be informed by a predicting person's abductive reasoning, inductive reasoning, deductive reasoning, and experience; and may be useful—if the predicting person is a knowledgeable person in the field.
The Delphi method is a technique for eliciting such expert-judgement-based predictions in a controlled way. This type of prediction might be perceived as consistent with statistical techniques in the sense that, at minimum, the "data" being used is the predicting expert's cognitive experiences forming an intuitive "probability curve."
== Statistics ==
In statistics, prediction is a part of statistical inference. One particular approach to such inference is known as predictive inference, but the prediction can be undertaken within any of the several approaches to statistical inference. Indeed, one possible description of statistics is that it provides a means of transferring knowledge about a sample of a population to the whole population, and to other related populations, which is not necessarily the same as prediction over time. When information is transferred across time, often to specific points in time, the process is known as forecasting. Forecasting usually requires time series methods, while prediction is often performed on cross-sectional data.
Statistical techniques used for prediction include regression and its various sub-categories such as linear regression, generalized linear models (logistic regression, Poisson regression, Probit regression), etc. In case of forecasting, autoregressive moving average models and vector autoregression models can be utilized. When these and/or related, generalized set of regression or machine learning methods are deployed in commercial usage, the field is known as predictive analytics.
In many applications, such as time series analysis, it is possible to estimate the models that generate the observations. If models can be expressed as transfer functions or in terms of state-space parameters then smoothed, filtered and predicted data estimates can be calculated. If the underlying generating models are linear then a minimum-variance Kalman filter and a minimum-variance smoother may be used to recover data of interest from noisy measurements. These techniques rely on one-step-ahead predictors (which minimise the variance of the prediction error). When the generating models are nonlinear then stepwise linearizations may be applied within Extended Kalman Filter and smoother recursions. However, in nonlinear cases, optimum minimum-variance performance guarantees no longer apply.
To use regression analysis for prediction, data are collected on the variable that is to be predicted, called the dependent variable or response variable, and on one or more variables whose values are hypothesized to influence it, called independent variables or explanatory variables. A functional form, often linear, is hypothesized for the postulated causal relationship, and the parameters of the function are estimated from the data—that is, are chosen so as to optimize is some way the fit of the function, thus parameterized, to the data. That is the estimation step. For the prediction step, explanatory variable values that are deemed relevant to future (or current but not yet observed) values of the dependent variable are input to the parameterized function to generate predictions for the dependent variable.
An unbiased performance estimate of a model can be obtained on hold-out test sets. The predictions can visually be compared to the ground truth in a parity plot.
== Science ==
In science, a prediction is a rigorous, often quantitative, statement, forecasting what would be observed under specific conditions; for example, according to theories of gravity, if an apple fell from a tree it would be seen to move towards the center of the Earth with a specified and constant acceleration. The scientific method is built on testing statements that are logical consequences of scientific theories. This is done through repeatable experiments or observational studies.
A scientific theory whose predictions are contradicted by observations and evidence will be rejected. New theories that generate many new predictions can more easily be supported or falsified (see predictive power). Notions that make no testable predictions are usually considered not to be part of science (protoscience or nescience) until testable predictions can be made.
Mathematical equations and models, and computer models, are frequently used to describe the past and future behaviour of a process within the boundaries of that model. In some cases the probability of an outcome, rather than a specific outcome, can be predicted, for example in much of quantum physics.
In microprocessors, branch prediction permits avoidance of pipeline emptying at branch instructions.
In engineering, possible failure modes are predicted and avoided by correcting the failure mechanism causing the failure.
Accurate prediction and forecasting are very difficult in some areas, such as natural disasters, pandemics, demography, population dynamics and meteorology. For example, it is possible to predict the occurrence of solar cycles, but their exact timing and magnitude is much more difficult (see picture to right).
In materials engineering it is also possible to predict the life time of a material with a mathematical model.
In medical science predictive and prognostic biomarkers can be used to predict patient outcomes in response to various treatment or the probability of a clinical event.
=== Hypothesis ===
Established science makes useful predictions which are often extremely reliable and accurate; for example, eclipses are routinely predicted.
New theories make predictions which allow them to be disproved by reality. For example, predicting the structure of crystals at the atomic level is a current research challenge. In the early 20th century the scientific consensus was that there existed an absolute frame of reference, which was given the name luminiferous ether. The existence of this absolute frame was deemed necessary for consistency with the established idea that the speed of light is constant. The famous Michelson–Morley experiment demonstrated that predictions deduced from this concept were not borne out in reality, thus disproving the theory of an absolute frame of reference. The special theory of relativity was proposed by Einstein as an explanation for the seeming inconsistency between the constancy of the speed of light and the non-existence of a special, preferred or absolute frame of reference.
Albert Einstein's theory of general relativity could not easily be tested as it did not produce any effects observable on a terrestrial scale. However, as one of the first tests of general relativity, the theory predicted that large masses such as stars would bend light, in contradiction to accepted theory; this was observed in a 1919 eclipse.
== Medicine and healthcare ==
=== Predictive medicine ===
=== Prognosis ===
=== Clinical prediction rules ===
== Finance ==
Mathematical models of stock market behaviour (and economic behaviour in general) are also unreliable in predicting future behaviour. Among other reasons, this is because economic events may span several years, and the world is changing over a similar time frame, thus invalidating the relevance of past observations to the present. Thus there are an extremely small number (of the order of 1) of relevant past data points from which to project the future. In addition, it is generally believed that stock market prices already take into account all the information available to predict the future, and subsequent movements must therefore be the result of unforeseen events. Consequently, it is extremely difficult for a stock investor to anticipate or predict a stock market boom, or a stock market crash. In contrast to predicting the actual stock return, forecasting of broad economic trends tends to have better accuracy. Such analysis is provided by both non-profit groups as well as by for-profit private institutions.
Some correlation has been seen between actual stock market movements and prediction data from large groups in surveys and prediction games.
An actuary uses actuarial science to assess and predict future business risk, such that the risk(s) can be mitigated. For example, in insurance an actuary would use a life table (which incorporates the historical experience of mortality rates and sometimes an estimate of future trends) to project life expectancy.
== Sports ==
Predicting the outcome of sporting events is a business which has grown in popularity in recent years. Handicappers predict the outcome of games using a variety of mathematical formulas, simulation models or qualitative analysis. Early, well known sports bettors, such as Jimmy the Greek, were believed to have access to information that gave them an edge. Information ranged from personal issues, such as gambling or drinking to undisclosed injuries; anything that may affect the performance of a player on the field.
Recent times have changed the way sports are predicted. Predictions now typically consist of two distinct approaches: Situational plays and statistical based models. Situational plays are much more difficult to measure because they usually involve the motivation of a team. Dan Gordon, noted handicapper, wrote "Without an emotional edge in a game in addition to value in a line, I won't put my money on it". These types of plays consist of: Betting on the home underdog, betting against Monday Night winners if they are a favorite next week, betting the underdog in "look ahead" games etc. As situational plays become more widely known they become less useful because they will impact the way the line is set.
The widespread use of technology has brought with it more modern sports betting systems. These systems are typically algorithms and simulation models based on regression analysis. Jeff Sagarin, a sports statistician, has brought attention to sports by having the results of his models published in USA Today. He is currently paid as a consultant by the Dallas Mavericks for his advice on lineups and the use of his Winval system, which evaluates free agents. Brian Burke, a former Navy fighter pilot turned sports statistician, has published his results of using regression analysis to predict the outcome of NFL games. Ken Pomeroy is widely accepted as a leading authority on college basketball statistics. His website includes his College Basketball Ratings, a tempo based statistics system. Some statisticians have become very famous for having successful prediction systems. Dare wrote "the effective odds for sports betting and horse racing are a direct result of human decisions and can therefore potentially exhibit consistent error". Unlike other games offered in a casino, prediction in sporting events can be both logical and consistent.
Other more advance models include those based on Bayesian networks, which are causal probabilistic models commonly used for risk analysis and decision support. Based on this kind of mathematical modelling, Constantinou et al., have developed models for predicting the outcome of association football matches. What makes these models interesting is that, apart from taking into consideration relevant historical data, they also incorporate all these vague subjective factors, like availability of key players, team fatigue, team motivation and so on. They provide the user with the ability to include their best guesses about things that there are no hard facts available. This additional information is then combined with historical facts to provide a revised prediction for future match outcomes. The initial results based on these modelling practices are encouraging since they have demonstrated consistent profitability against published market odds.
Nowadays sport betting is a huge business; there are many websites (systems) alongside betting sites, which give tips or predictions for future games. Some of these prediction websites (tipsters) are based on human predictions, but others on computer software sometimes called prediction robots or bots. Prediction bots can use different amount of data and algorithms and because of that their accuracy may vary.
These days, with the development of artificial intelligence, it has become possible to create more consistent predictions using statistics. Especially in the field of sports competitions, the impact of artificial intelligence has created a noticeable consistency rate. On the science of AI soccer predictions, an initiative called soccerseer.com, one of the most successful systems in this sense, manages to predict the results of football competitions with up to 75% accuracy with artificial intelligence.
== Social science ==
Prediction in the non-economic social sciences differs from the natural sciences and includes multiple alternative methods such as trend projection, forecasting, scenario-building and Delphi surveys. The oil company Shell is particularly well known for its scenario-building activities.
One reason for the peculiarity of societal prediction is that in the social sciences, "predictors are part of the social context about which they are trying to make a prediction and may influence that context in the process". As a consequence, societal predictions can become self-destructing. For example, a forecast that a large percentage of a population will become HIV infected based on existing trends may cause more people to avoid risky behavior and thus reduce the HIV infection rate, invalidating the forecast (which might have remained correct if it had not been publicly known). Or, a prediction that cybersecurity will become a major issue may cause organizations to implement more security cybersecurity measures, thus limiting the issue.
In politics it is common to attempt to predict the outcome of elections via political forecasting techniques (or assess the popularity of politicians) through the use of opinion polls. Prediction games have been used by many corporations and governments to learn about the most likely outcome of future events.
== Prophecy ==
Predictions have often been made, from antiquity until the present, by using paranormal or supernatural means such as prophecy or by observing omens. Methods including water divining, astrology, numerology, fortune telling, interpretation of dreams, and many other forms of divination, have been used for millennia to attempt to predict the future. These means of prediction have not been proven by scientific experiments.
In literature, vision and prophecy are literary devices used to present a possible timeline of future events. They can be distinguished by vision referring to what an individual sees happen. The book of Revelation, in the New Testament, thus uses vision as a literary device in this regard. It is also prophecy or prophetic literature when it is related by an individual in a sermon or other public forum.
Divination is the attempt to gain insight into a question or situation by way of an occultic standardized process or ritual. It is an integral part of witchcraft and has been used in various forms for thousands of years. Diviners ascertain their interpretations of how a querent should proceed by reading signs, events, or omens, or through alleged contact with a supernatural agency, most often described as an angel or a god though viewed by Christians and Jews as a fallen angel or demon.
== Fiction ==
Fiction (especially fantasy, forecasting and science fiction) often features instances of prediction achieved by unconventional means. Science fiction of the past predicted various modern technologies.
In fantasy literature, predictions are often obtained through magic or prophecy, sometimes referring back to old traditions. For example, in J. R. R. Tolkien's The Lord of the Rings, many of the characters possess an awareness of events extending into the future, sometimes as prophecies, sometimes as more-or-less vague 'feelings'. The character Galadriel, in addition, employs a water "mirror" to show images, sometimes of possible future events.
In some of Philip K. Dick's stories, mutant humans called precogs can foresee the future (ranging from days to years). In the story called The Golden Man, an exceptional mutant can predict the future to an indefinite range (presumably up to his death), and thus becomes completely non-human, an animal that follows the predicted paths automatically. Precogs also play an essential role in another of Dick's stories, The Minority Report, which was turned into a film by Steven Spielberg in 2002.
In the Foundation series by Isaac Asimov, a mathematician finds out that historical events (up to some detail) can be theoretically modelled using equations, and then spends years trying to put the theory in practice. The new science of psychohistory founded upon his success can simulate history and extrapolate the present into the future.
In Frank Herbert's sequels to 1965's Dune, his characters are dealing with the repercussions of being able to see the possible futures and select amongst them. Herbert sees this as a trap of stagnation, and his characters follow a so-called "Golden Path" out of the trap.
In Ursula K. Le Guin's The Left Hand of Darkness, the humanoid inhabitants of planet Gethen have mastered the art of prophecy and routinely produce data on past, present or future events on request. In this story, this was a minor plot device.
== Poetry ==
For the ancients, prediction, prophesy, and poetry were often intertwined. Prophecies were given in verse, and a word for poet in Latin is “vates” or prophet. Both poets and prophets claimed to be inspired by forces outside themselves. In contemporary cultures, theological revelation and poetry are typically seen as distinct and often even as opposed to each other. Yet the two still are often understood together as symbiotic in their origins, aims, and purposes.
== See also ==
Expectation – Anticipation that a future event or consequence is likelyPages displaying short descriptions of redirect targets
Forecasting – Making predictions based on available data
Futures studies – Study of postulating possible, probable, and preferable futures
Omen – Portent, harbinger
Oracle – Provider of prophecies or insights
Predictability – Degree to which a correct prediction of a system's state can be made
Prediction market – Platforms for betting on events
Predictive modelling – Form of modelling that uses statistics to predict outcomes
Prognosis – Medical term for the likely development of a disease
Prognostics – prediction of the time at which a system or a component will malfunctionPages displaying wikidata descriptions as a fallback
Reference class forecasting – Method of predicting the future
Regression analysis – Set of statistical processes for estimating the relationships among variables
Thought experiment – Hypothetical situation
Trend estimation – Statistical technique to aid interpretation of dataPages displaying short descriptions of redirect targets
== Footnotes ==
== Further reading ==
Ialenti, Vincent (2020). Deep Time Reckoning: How Future Thinking Can Help Earth Now. The MIT Press. ISBN 9780262539265.
Rescher, Nicholas (1998). Predicting the future: An introduction to the theory of forecasting. State University of New York Press. ISBN 0-7914-3553-9.
Tetlock, Philip E.; Gardner, Dan (2016). Superforecasting: The Art and Science of Prediction. Crown. ISBN 978-0804136716. | Wikipedia/Prediction_in_science |
The Young–Helmholtz theory (based on the work of Thomas Young and Hermann von Helmholtz in the 19th century), also known as the trichromatic theory, is a theory of trichromatic color vision – the manner in which the visual system gives rise to the phenomenological experience of color. In 1802, Young postulated the existence of three types of photoreceptors (now known as cone cells) in the eye, with different but overlapping response to different wavelengths of visible light.
Hermann von Helmholtz developed the theory further in 1850: that the three types of cone photoreceptors could be classified as short-preferring (violet), middle-preferring (green), and long-preferring (red), according to their response to the wavelengths of light striking the retina. The relative strengths of the signals detected by the three types of cones are interpreted by the brain as a visible color.
For instance, yellow light uses different proportions of red and green, but little blue, so any hue depends on a mix of all three cones, for example, a strong red-sensitive, medium green-sensitive, and low blue-sensitive. Moreover, the intensity of colors can be changed without changing their hues, since intensity depends on the frequency of discharge to the brain, as a blue-green can be brightened but retain the same hue. The system is not perfect, as it does not distinguish yellow from a red-green mixture, but can powerfully detect subtle environmental changes.
In 1857, James Clerk Maxwell used the recently developed linear algebra to offer a mathematical proof of the Young–Helmholtz theory.
The existence of cells sensitive to three different wavelength ranges (most sensitive to yellowish green, cyanish-green, and blue – not red, green and blue) was first shown in 1956 by Gunnar Svaetichin. In 1983 it was validated in human retinas in an experiment by Herbert Dartnall, James Bowmaker, and John Mollon, who obtained microspectrophotopic readings of single eye cone cells. Earlier evidence for the theory had been obtained by looking at light reflected from the retinas of living humans, and absorption of light by retinal cells removed from corpses.
While Young is often credited as the progenitor of trichromatic color theory, a theory of color vision by George Palmer is mostly analogous to Young's, but precedes it by a quarter century. In his Theory of Colors and Vision (1777) and later in his Theory of Light (1786), Palmer claims that the retina has 3 classes of particles that selectively absorb red, yellow and blue rays. The unequal motion of these particles evokes color, and the equal motion thereof evokes white. However, Palmer also claimed that light itself is compounded of only three distinct rays: red, yellow and blue, which differs from the modern understanding (and that of Young), that light is a continuous visible spectrum.
== References == | Wikipedia/Young–Helmholtz_theory |
Xylem is one of the two types of transport tissue in vascular plants, the other being phloem; both of these are part of the vascular bundle. The basic function of the xylem is to transport water upward from the roots to parts of the plants such as stems and leaves, but it also transports nutrients. The word xylem is derived from the Ancient Greek word ξύλον (xúlon), meaning "wood"; the best-known wood organism is plants, though it is found throughout a plant. The term was introduced by Carl Nägeli in 1858.
== Structure ==
The most distinctive xylem cells are the long tracheary elements that transport water. Tracheids and vessel elements are distinguished by their shape; vessel elements are shorter, and are connected together into long tubes that are called vessels.
Wood also contains two other type of cells: parenchyma and fibers.
Xylem can be found:
in vascular bundles, present in non-woody plants and non-woody parts of woody plants
in secondary xylem, laid down by a meristem called the vascular cambium in woody plants
as part of a stelar arrangement not divided into bundles, as in many ferns.
In transitional stages of plants with secondary growth, the first two categories are not mutually exclusive, although usually a vascular bundle will contain primary xylem only.
The branching pattern exhibited by xylem follows Murray's law.
== Primary and secondary xylem ==
Primary xylem is formed during primary growth from procambium. It includes protoxylem and metaxylem. Metaxylem develops after the protoxylem but before secondary xylem. Metaxylem has wider vessels and tracheids than protoxylem.
Secondary xylem is formed during secondary growth from vascular cambium. Although secondary xylem is also found in members of the gymnosperm groups Gnetophyta and Ginkgophyta and to a lesser extent in members of the Cycadophyta, the two main groups in which secondary xylem can be found are:
conifers (Coniferae): there are approximately 600 known species of conifers. All species have secondary xylem, which is relatively uniform in structure throughout this group. Many conifers become tall trees: the secondary xylem of such trees is used and marketed as softwood.
angiosperms (Angiospermae): there are approximately 250,000 known species of angiosperms. Within this group secondary xylem is rare in the monocots. Many non-monocot angiosperms become trees, and the secondary xylem of these is used and marketed as hardwood.
== Main function – upwards water transport ==
The xylem, vessels and tracheids of the roots, stems and leaves are interconnected to form a continuous system of water-conducting channels reaching all parts of the plants. The system transports water and soluble mineral nutrients from the roots throughout the plant. It is also used to replace water lost during transpiration and photosynthesis. Xylem sap consists mainly of water and inorganic ions, although it can also contain a number of organic chemicals as well. The transport is passive, not powered by energy spent by the tracheary elements themselves, which are dead by maturity and no longer have living contents. Transporting sap upwards becomes more difficult as the height of a plant increases and upwards transport of water by xylem is considered to limit the maximum height of trees. Three phenomena cause xylem sap to flow:
Pressure flow hypothesis: Sugars produced in the leaves and other green tissues are kept in the phloem system, creating a solute pressure differential versus the xylem system carrying a far lower load of solutes—water and minerals. The phloem pressure can rise to several MPa, far higher than atmospheric pressure. Selective inter-connection between these systems allows this high solute concentration in the phloem to draw xylem fluid upwards by negative pressure.
Transpirational pull: Similarly, the evaporation of water from the surfaces of mesophyll cells to the atmosphere also creates a negative pressure at the top of a plant. This causes millions of minute menisci to form in the mesophyll cell wall. The resulting surface tension causes a negative pressure or tension in the xylem that pulls the water from the roots and soil.
Root pressure: If the water potential of the root cells is more negative than that of the soil, usually due to high concentrations of solute, water can move by osmosis into the root from the soil. This causes a positive pressure that forces sap up the xylem towards the leaves. In some circumstances, the sap will be forced from the leaf through a hydathode in a phenomenon known as guttation. Root pressure is highest in the morning before the opening of stomata and allow transpiration to begin. Different plant species can have different root pressures even in a similar environment; examples include up to 145 kPa in Vitis riparia but around zero in Celastrus orbiculatus.
The primary force that creates the capillary action movement of water upwards in plants is the adhesion between the water and the surface of the xylem conduits. Capillary action provides the force that establishes an equilibrium configuration, balancing gravity. When transpiration removes water at the top, the flow is needed to return to the equilibrium.
Transpirational pull results from the evaporation of water from the surfaces of cells in the leaves. This evaporation causes the surface of the water to recess into the pores of the cell wall. By capillary action, the water forms concave menisci inside the pores. The high surface tension of water pulls the concavity outwards, generating enough force to lift water as high as a hundred meters from ground level to a tree's highest branches.
Transpirational pull requires that the vessels transporting the water be very small in diameter; otherwise, cavitation would break the water column. And as water evaporates from leaves, more is drawn up through the plant to replace it. When the water pressure within the xylem reaches extreme levels due to low water input from the roots (if, for example, the soil is dry), then the gases come out of solution and form a bubble – an embolism forms, which will spread quickly to other adjacent cells, unless bordered pits are present (these have a plug-like structure called a torus, that seals off the opening between adjacent cells and stops the embolism from spreading). Even after an embolism has occurred, plants are able to refill the xylem and restore the functionality.
=== Cohesion-tension theory ===
The cohesion-tension theory is a theory of intermolecular attraction that explains the process of water flow upwards (against the force of gravity) through the xylem of plants. It was proposed in 1894 by John Joly and Henry Horatio Dixon. Despite numerous objections, this is the most widely accepted theory for the transport of water through a plant's vascular system based on the classical research of Dixon-Joly (1894), Eugen Askenasy (1845–1903) (1895), and Dixon (1914,1924).
Water is a polar molecule. When two water molecules approach one another, the slightly negatively charged oxygen atom of one forms a hydrogen bond with a slightly positively charged hydrogen atom in the other. This attractive force, along with other intermolecular forces, is one of the principal factors responsible for the occurrence of surface tension in liquid water. It also allows plants to draw water from the root through the xylem to the leaf.
Water is constantly lost through transpiration from the leaf. When one water molecule is lost another is pulled along by the processes of cohesion and tension. Transpiration pull, utilizing capillary action and the inherent surface tension of water, is the primary mechanism of water movement in plants. However, it is not the only mechanism involved. Any use of water in leaves forces water to move into them.
Transpiration in leaves creates tension (differential pressure) in the cell walls of mesophyll cells. Because of this tension, water is being pulled up from the roots into the leaves, helped by cohesion (the pull between individual water molecules, due to hydrogen bonds) and adhesion (the stickiness between water molecules and the hydrophilic cell walls of plants). This mechanism of water flow works because of water potential (water flows from high to low potential), and the rules of simple diffusion.
Over the past century, there has been a great deal of research regarding the mechanism of xylem sap transport; today, most plant scientists continue to agree that the cohesion-tension theory best explains this process, but multiforce theories that hypothesize several alternative mechanisms have been suggested, including longitudinal cellular and xylem osmotic pressure gradients, axial potential gradients in the vessels, and gel- and gas-bubble-supported interfacial gradients.
=== Measurement of pressure ===
Until recently, the differential pressure (suction) of transpirational pull could only be measured indirectly, by applying external pressure with a pressure bomb to counteract it. When the technology to perform direct measurements with a pressure probe was developed, there was initially some doubt about whether the classic theory was correct, because some workers were unable to demonstrate negative pressures. More recent measurements do tend to validate the classic theory, for the most part. Xylem transport is driven by a combination of transpirational pull from above and root pressure from below, which makes the interpretation of measurements more complicated.
== Evolution ==
Xylem appeared early in the history of terrestrial plant life. Fossil plants with anatomically preserved xylem are known from the Silurian (more than 400 million years ago), and trace fossils resembling individual xylem cells may be found in earlier Ordovician rocks. The earliest true and recognizable xylem consists of tracheids with a helical-annular reinforcing layer added to the cell wall. This is the only type of xylem found in the earliest vascular plants, and this type of cell continues to be found in the protoxylem (first-formed xylem) of all living groups of vascular plants. Several groups of plants later developed pitted tracheid cells independently through convergent evolution. In living plants, pitted tracheids do not appear in development until the maturation of the metaxylem (following the protoxylem).
In most plants, pitted tracheids function as the primary transport cells. The other type of vascular element, found in angiosperms, is the vessel element. Vessel elements are joined end to end to form vessels in which water flows unimpeded, as in a pipe. The presence of xylem vessels (also called trachea) is considered to be one of the key innovations that led to the success of the angiosperms. However, the occurrence of vessel elements is not restricted to angiosperms, and they are absent in some archaic or "basal" lineages of the angiosperms: (e.g., Amborellaceae, Tetracentraceae, Trochodendraceae, and Winteraceae), and their secondary xylem is described by Arthur Cronquist as "primitively vesselless". Cronquist considered the vessels of Gnetum to be convergent with those of angiosperms. Whether the absence of vessels in basal angiosperms is a primitive condition is contested, the alternative hypothesis states that vessel elements originated in a precursor to the angiosperms and were subsequently lost.
To photosynthesize, plants must absorb CO2 from the atmosphere. However, this comes at a price: while stomata are open to allow CO2 to enter, water can evaporate. Water is lost much faster than CO2 is absorbed, so plants need to replace it, and have developed systems to transport water from the moist soil to the site of photosynthesis. Early plants sucked water between the walls of their cells, then evolved the ability to control water loss (and CO2 acquisition) through the use of stomata. Specialized water transport tissues soon evolved in the form of hydroids, tracheids, then secondary xylem, followed by an endodermis and ultimately vessels.
The high CO2 levels of Silurian-Devonian times, when plants were first colonizing land, meant that the need for water was relatively low. As CO2 was withdrawn from the atmosphere by plants, more water was lost in its capture, and more elegant transport mechanisms evolved. As water transport mechanisms, and waterproof cuticles, evolved, plants could survive without being continually covered by a film of water. This transition from poikilohydry to homoiohydry opened up new potential for colonization. Plants then needed a robust internal structure that held long narrow channels for transporting water from the soil to all the different parts of the above-soil plant, especially to the parts where photosynthesis occurred.
During the Silurian, CO2 was readily available, so little water needed expending to acquire it. By the end of the Carboniferous, when CO2 levels had lowered to something approaching today's, around 17 times more water was lost per unit of CO2 uptake. However, even in these "easy" early days, water was at a premium, and had to be transported to parts of the plant from the wet soil to avoid desiccation. This early water transport took advantage of the cohesion-tension mechanism inherent in water. Water has a tendency to diffuse to areas that are drier, and this process is accelerated when water can be wicked along a fabric with small spaces. In small passages, such as that between the plant cell walls (or in tracheids), a column of water behaves like rubber – when molecules evaporate from one end, they pull the molecules behind them along the channels. Therefore, transpiration alone provided the driving force for water transport in early plants. However, without dedicated transport vessels, the cohesion-tension mechanism cannot transport water more than about 2 cm, severely limiting the size of the earliest plants. This process demands a steady supply of water from one end, to maintain the chains; to avoid exhausting it, plants developed a waterproof cuticle. Early cuticle may not have had pores but did not cover the entire plant surface, so that gas exchange could continue. However, dehydration at times was inevitable; early plants cope with this by having a lot of water stored between their cell walls, and when it comes to it sticking out the tough times by putting life "on hold" until more water is supplied.
To be free from the constraints of small size and constant moisture that the parenchymatic transport system inflicted, plants needed a more efficient water transport system. During the early Silurian, they developed specialized cells, which were lignified (or bore similar chemical compounds) to avoid implosion; this process coincided with cell death, allowing their innards to be emptied and water to be passed through them. These wider, dead, empty cells were a million times more conductive than the inter-cell method, giving the potential for transport over longer distances, and higher CO2 diffusion rates.
The earliest macrofossils to bear water-transport tubes are Silurian plants placed in the genus Cooksonia. The early Devonian pretracheophytes Aglaophyton and Horneophyton have structures very similar to the hydroids of modern mosses.
Plants continued to innovate new ways of reducing the resistance to flow within their cells, thereby increasing the efficiency of their water transport. Bands on the walls of tubes, in fact apparent from the early Silurian onwards, are an early improvisation to aid the easy flow of water. Banded tubes, as well as tubes with pits in their walls, were lignified and, when they form single celled conduits, are considered to be tracheids. These, the "next generation" of transport cell design, have a more rigid structure than hydroids, allowing them to cope with higher levels of water pressure. Tracheids may have a single evolutionary origin, possibly within the hornworts, uniting all tracheophytes (but they may have evolved more than once).
Water transport requires regulation, and dynamic control is provided by stomata.
By adjusting the amount of gas exchange, they can restrict the amount of water lost through transpiration. This is an important role where water supply is not constant, and indeed stomata appear to have evolved before tracheids, being present in the non-vascular hornworts.
An endodermis probably evolved during the Silu-Devonian, but the first fossil evidence for such a structure is Carboniferous. This structure in the roots covers the water transport tissue and regulates ion exchange (and prevents unwanted pathogens etc. from entering the water transport system). The endodermis can also provide an upwards pressure, forcing water out of the roots when transpiration is not enough of a driver.
Once plants had evolved this level of controlled water transport, they were truly homoiohydric, able to extract water from their environment through root-like organs rather than relying on a film of surface moisture, enabling them to grow to much greater size. As a result of their independence from their surroundings, they lost their ability to survive desiccation – a costly trait to retain.
During the Devonian, maximum xylem diameter increased with time, with the minimum diameter remaining pretty constant. By the middle Devonian, the tracheid diameter of some plant lineages (Zosterophyllophytes) had plateaued. Wider tracheids allow water to be transported faster, but the overall transport rate depends also on the overall cross-sectional area of the xylem bundle itself. The increase in vascular bundle thickness further seems to correlate with the width of plant axes, and plant height; it is also closely related to the appearance of leaves and increased stomatal density, both of which would increase the demand for water.
While wider tracheids with robust walls make it possible to achieve higher water transport tensions, this increases the likelihood of cavitation. Cavitation occurs when a bubble of air forms within a vessel, breaking the bonds between chains of water molecules and preventing them from pulling more water up with their cohesive tension. A tracheid, once cavitated, cannot have its embolism removed and return to service (except in a few advanced angiosperms which have developed a mechanism of doing so). Therefore, it is well worth plants' while to avoid cavitation occurring. For this reason, pits in tracheid walls have very small diameters, to prevent air entering and allowing bubbles to nucleate. Freeze-thaw cycles are a major cause of cavitation. Damage to a tracheid's wall almost inevitably leads to air leaking in and cavitation, hence the importance of many tracheids working in parallel.
Once cavitation has occurred, plants have a range of mechanisms to contain the damage. Small pits link adjacent conduits to allow fluid to flow between them, but not air – although these pits, which prevent the spread of embolism, are also a major cause of them. These pitted surfaces further reduce the flow of water through the xylem by as much as 30%. The diversification of xylem strand shapes with tracheid network topologies increasingly resistant to the spread of embolism likely facilitated increases in plant size and the colonization of drier habitats during the Devonian radiation. Conifers, by the Jurassic, developed bordered pits had valve-like structures to isolate cavitated elements. These torus-margo structures have an impermeable disc (torus) suspended by a permeable membrane (margo) between two adjacent pores. When a tracheid on one side depressurizes, the disc is sucked into the pore on that side, and blocks further flow. Other plants simply tolerate cavitation. For instance, oaks grow a ring of wide vessels at the start of each spring, none of which survive the winter frosts. Maples use root pressure each spring to force sap upwards from the roots, squeezing out any air bubbles.
Growing to height also employed another trait of tracheids – the support offered by their lignified walls. Defunct tracheids were retained to form a strong, woody stem, produced in most instances by a secondary xylem. However, in early plants, tracheids were too mechanically vulnerable, and retained a central position, with a layer of tough sclerenchyma on the outer rim of the stems. Even when tracheids do take a structural role, they are supported by sclerenchymatic tissue.
Tracheids end with walls, which impose a great deal of resistance on flow; vessel members have perforated end walls, and are arranged in series to operate as if they were one continuous vessel. The function of end walls, which were the default state in the Devonian, was probably to avoid embolisms. An embolism is where an air bubble is created in a tracheid. This may happen as a result of freezing, or by gases dissolving out of solution. Once an embolism is formed, it usually cannot be removed (but see later); the affected cell cannot pull water up, and is rendered useless.
End walls excluded, the tracheids of prevascular plants were able to operate under the same hydraulic conductivity as those of the first vascular plant, Cooksonia.
The size of tracheids is limited as they comprise a single cell; this limits their length, which in turn limits their maximum useful diameter to 80 μm. Conductivity grows with the fourth power of diameter, so increased diameter has huge rewards; vessel elements, consisting of a number of cells, joined at their ends, overcame this limit and allowed larger tubes to form, reaching diameters of up to 500 μm, and lengths of up to 10 m.
Vessels first evolved during the dry, low CO2 periods of the late Permian, in the horsetails, ferns and Selaginellales independently, and later appeared in the mid Cretaceous in angiosperms and gnetophytes.
Vessels allow the same cross-sectional area of wood to transport around a hundred times more water than tracheids! This allowed plants to fill more of their stems with structural fibers, and also opened a new niche to vines, which could transport water without being as thick as the tree they grew on. Despite these advantages, tracheid-based wood is a lot lighter, thus cheaper to make, as vessels need to be much more reinforced to avoid cavitation.
== Development ==
Xylem development can be described by four terms: centrarch, exarch, endarch and mesarch. As it develops in young plants, its nature changes from protoxylem to metaxylem (i.e. from first xylem to after xylem). The patterns in which protoxylem and metaxylem are arranged are essential in studying plant morphology.
=== Protoxylem and metaxylem ===
As a young vascular plant grows, one or more strands of primary xylem form in its stems and roots. The first xylem to develop is called 'protoxylem'. In appearance, protoxylem is usually distinguished by narrower vessels formed of smaller cells. Some of these cells have walls that contain thickenings in the form of rings or helices. Functionally, protoxylem can extend: the cells can grow in size and develop while a stem or root is elongating. Later, 'metaxylem' develops in the strands of xylem. Metaxylem vessels and cells are usually larger; the cells have thickenings typically either in the form of ladderlike transverse bars (scalariform) or continuous sheets except for holes or pits (pitted). Functionally, metaxylem completes its development after elongation ceases when the cells no longer need to grow in size.
=== Patterns of protoxylem and metaxylem ===
There are four primary patterns to the arrangement of protoxylem and metaxylem in stems and roots.
Centrarch refers to the case in which the primary xylem forms a single cylinder in the center of the stem and develops from the center outwards. The protoxylem is thus found in the central core, and the metaxylem is in a cylinder around it. This pattern was common in early land plants, such as "rhyniophytes", but is not present in any living plants.
The other three terms are used where there is more than one strand of primary xylem.
Exarch is used when there is more than one strand of primary xylem in a stem or root, and the xylem develops from the outside inwards towards the center, i.e., centripetally. The metaxylem is thus closest to the center of the stem or root, and the protoxylem is closest to the periphery. The roots of vascular plants are generally considered to have exarch development.
Endarch is used when there is more than one strand of primary xylem in a stem or root, and the xylem develops from the inside outwards towards the periphery, i.e., centrifugally. The protoxylem is thus closest to the center of the stem or root, and the metaxylem is closest to the periphery. The stems of seed plants typically have endarch development.
Mesarch is used when there is more than one strand of primary xylem in a stem or root, and the xylem develops from the middle of a strand in both directions. The metaxylem is thus on both the peripheral and central sides of the strand, with the protoxylem between the metaxylem (possibly surrounded by it). The leaves and stems of many ferns have mesarch development.
== History ==
In his book De plantis libri XVI (On Plants, in 16 books) (1583), the Italian physician and botanist Andrea Cesalpino proposed that plants draw water from soil not by magnetism (ut magnes ferrum trahit, as magnetic iron attracts) nor by suction (vacuum), but by absorption, as occurs in the case of linen, sponges, or powders. The Italian biologist Marcello Malpighi was the first person to describe and illustrate xylem vessels, which he did in his book Anatome plantarum ... (1675). Although Malpighi believed that xylem contained only air, the British physician and botanist Nehemiah Grew, who was Malpighi's contemporary, believed that sap ascended both through the bark and through the xylem. However, according to Grew, capillary action in the xylem would raise the sap by only a few inches; to raise the sap to the top of a tree, Grew proposed that the parenchymal cells become turgid and thereby not only squeeze the sap in the tracheids but force some sap from the parenchyma into the tracheids. In 1727, English clergyman and botanist Stephen Hales showed that transpiration by a plant's leaves causes water to move through its xylem. By 1891, the Polish-German botanist Eduard Strasburger had shown that the transport of water in plants did not require the xylem cells to be alive.
== See also ==
Soil plant atmosphere continuum
Suction
Tylosis
Vascular tissue
Xylem sap
== Explanatory notes ==
== References ==
=== Citations ===
=== General references ===
C. Wei; E. Steudle; M. T. Tyree; P. M. Lintilhac (May 2001). "The essentials of direct xylem pressure measurement". Plant, Cell and Environment. 24 (5): 549–555. Bibcode:2001PCEnv..24..549W. doi:10.1046/j.1365-3040.2001.00697.x. S2CID 5039439. is the main source used for the paragraph on recent research.
N. Michele Holbrook; Michael J. Burns; Christopher B. Field (November 1995). "Negative Xylem Pressures in Plants: A Test of the Balancing Pressure Technique". Science. 270 (5239): 1193–4. Bibcode:1995Sci...270.1193H. doi:10.1126/science.270.5239.1193. S2CID 97217181. is the first published independent test showing the Scholander bomb actually does measure the tension in the xylem.
Pockman, W.T.; J.S. Sperry; J.W. O'Leary (December 1995). "Sustained and significant negative water pressure in xylem". Nature. 378 (6558): 715–6. Bibcode:1995Natur.378..715P. doi:10.1038/378715a0. S2CID 31357329. is the second published independent test showing the Scholander bomb actually does measure the tension in the xylem.
Campbell, Neil A.; Jane B. Reece (2002). Biology (6th ed.). Benjamin Cummings. ISBN 978-0-8053-6624-2.
Kenrick, Paul; Crane, Peter R. (1997). The Origin and Early Diversification of Land Plants: A Cladistic Study. Washington, D. C.: Smithsonian Institution Press. ISBN 978-1-56098-730-7.
Muhammad, A. F.; R. Sattler (1982). "Vessel Structure of Gnetum and the Origin of Angiosperms". American Journal of Botany. 69 (6): 1004–21. doi:10.2307/2442898. JSTOR 2442898.
Melvin T. Tyree; Martin H. Zimmermann (2003). Xylem Structure and the Ascent of Sap (2nd ed.). Springer. ISBN 978-3-540-43354-5. recent update of the classic book on xylem transport by the late Martin Zimmermann
== External links ==
Media related to Xylem at Wikimedia Commons | Wikipedia/Cohesion-tension_theory |
A Bachelor of Medicine, Bachelor of Surgery (Latin: Medicinae Baccalaureus, Baccalaureus Chirurgiae; MBBS, also abbreviated as BM BS, MB ChB, MB BCh, or MB BChir) is a medical degree granted by medical schools or universities in countries that adhere to the United Kingdom's higher education tradition. Despite the historical distinction in nomenclature, these degrees are typically combined and conferred together. This degree is usually awarded as an undergraduate degree, but it can also be awarded at graduate-level medical institutions. The typical duration for completion is five to six years.
A Bachelor of Medicine (BMed, BM, or MB) is an undergraduate medical degree awarded by medical schools in countries following the tradition of China. The completion period for this degree is generally five to six years. The term 'Medicine' in this context encompasses the broader field of medical science and practice, rather than specifically internal medicine. Consequently, graduates with a BMed degree are qualified to practise surgery. The BMed degree serves as the primary medical qualification, and individuals holding it may pursue further professional education, such as a Master of Medical Science or a Doctor of Medical Science (equivalent to a PhD).
Both degrees are considered equivalent to the Doctor of Medicine degree typically conferred by universities in North America. In the United States, doctors trained in some osteopathic medicine programs receive the Doctor of Osteopathic Medicine degree. For practical purposes, all these degrees (MBBS/BMed/MD/DO) are considered to be equivalent.
== History and nature ==
The degree is currently awarded in institutions in the United Kingdom and countries formerly part of the British Empire.
Historically, Bachelor of Medicine was also the primary medical degree conferred by institutions in the United States and Canada, such as the University of Pennsylvania, Harvard University, the University of Toronto, the University of Maryland, and Columbia University. Several early North American medical schools were (for the most part) founded by physicians and surgeons who had trained in England and Scotland. University medical education in England culminated with the Bachelor of Medicine qualification and in Scotland the Doctor of Medicine. In the mid-19th century, the public bodies that regulated medical practice required practitioners in Scotland and England to hold the dual Bachelor of Medicine and Bachelor of Surgery degrees. Over the course of the 19th century, North American medical schools switched to the tradition of the ancient universities of Scotland and began conferring Doctor of Medicine rather than Bachelor of Medicine.
In the countries that award bachelor's degrees in medicine, however, Doctor of Medicine denotes a holder of a junior doctorate and is reserved for medical practitioners who undertake research and submit a thesis in the field of medicine. Nevertheless, those holding Bachelor of Medicine, Bachelor of Surgery are usually referred to by the courtesy title of "Doctor" and use the prefix "Dr.", whether or not they also hold a Ph.D. or DSc.
In many countries, the degrees are awarded after an undergraduate course lasting five or six years. For example, most Chinese universities offering medical degrees provide undergraduate courses lasting six years. In some cases, a graduate in another discipline may subsequently enter a special graduate-entry medical course, reduced in duration to account for relevant material covered or learning skills acquired during the first degree. In some cases the old first-year courses (for six-year degrees) in the basic sciences of physics, chemistry, and biology have been abolished: that standard has to be reached by school examinations before entry. However, in most countries, a newly graduated Bachelor of Medicine and Surgery must spend a specified period in internship before he or she can obtain full registration as a licensed medical practitioner.
== Naming ==
The names and abbreviations given to these degrees depend on the institution, awarding body or country, and vary widely. This is mostly for reasons of tradition rather than to indicate any difference between the relative levels of the degrees. They are considered equivalent.
If the awarding body titles the degrees in Latin, the degrees are commonly named Medicinae Baccalaureus, Chirurgiae Baccalaureus; Medicinae Baccalaureus et Chirurgiae Baccalaureus; or Baccalaureus in Medicina et in Chirurgia; abbreviated as MB ChB, MB BCh or otherwise. If titled in English, they are named Bachelor of Medicine, Bachelor of Surgery; Bachelor of Medicine and Bachelor of Surgery; or Bachelor of Medicine and Surgery; usually abbreviated as MB BS, and sometimes as BM BS, even though most MB BS-awarding institutions do not use Latin to name their degrees.
Below are described the specific names used, arranged by country.
=== Australia ===
Historically, Australian medical schools have followed the British tradition by conferring the degrees of Bachelor of Medicine and Bachelor of Surgery (MBBS) to its graduates whilst reserving the title of Doctor of Medicine (MD) for their research training degree, analogous to the PhD, or for their honorary doctorates. Although the majority of Australian MBBS degrees have been graduate programs since the 1990s, under the previous Australian Qualifications Framework (AQF) they remained categorised as Level 7 Bachelor's degrees together with other undergraduate programs.
The latest version of the AQF includes the new category of Level 9 Master's (Extended) degrees which permits the use of the term 'Doctor' in the styling of the degree title of relevant professional programs. As a result, most undergraduate Australian medical schools have replaced their MBBS degrees with a combined degree that ends with the MD (e.g. the Bachelor of Medical Studies / Doctor of Medicine at The University of New South Wales or the Bachelor of Medical Science and Doctor of Medicine at Monash University) or switched to graduate only MD pathways, to resolve the previous anomalous nomenclature. Even still, Curtin University and James Cook University both still offer the MBBS degree. With the introduction of the Master's level MD, universities have also renamed their previous medical research doctorates. The University of Melbourne was the first to introduce the MD in 2011 as a basic medical degree, and has renamed its research degree to Doctor of Medical Science (DMedSc).
=== Bahrain ===
The Medical University of Bahrain or RCSI-Bahrain is a constituent university of the Royal College of Surgeons in Ireland (RCSI) and awards its graduates the MB, BCh, BAO (Hons), the same degree awarded to graduates at RCSI.
=== Bangladesh ===
All medical schools in Bangladesh award MBBS.
=== Barbados ===
The Bridgetown International University, Victoria University of Barbados, American University of Barbados School of Medicine, and University of the West Indies Faculty of Medicine all award the MBBS.
=== China ===
In China, medical undergraduates are awarded a Bachelor of Medicine (MB, also BMed, and BM) in Clinical Medicine for a course of study lasting five years for native Chinese students and six years for international/foreign students, including internship. International students may take the program in English or Chinese. Some medical schools also award MBBS degrees, but only for the international students. In total, 247 universities are authorized to award medical degrees. All 247 universities are recognized by most of the medical councils around the world and by ECFMG. By August 2022, 136 universities have passed the process of Accreditation of Medical Education from the Ministry of Education of China. The universities awarding MB and MBBS degrees are at the list of medical schools in China.
=== Egypt ===
All Egyptian medical schools, public and private, award an MB BCh as the basic medical degree after completion of five academic and clinical study years followed by two years of obligatory clinical rotations (the MB BCh is issued only after the completion of the clinical rotations) with total of seven years both academic, clinical study and clinical rotations.
=== France ===
French students get permitted access to medical studies when succeeding the competitive examination occurring at the end of their first year of studies. They spend their second and third year at their medical school where they learn physiology, semiology and the basics of medical examination. From their fourth year, they begin their rotations in teaching hospitals where they assist junior and senior physicians and learn their art. At the end of their sixth year, they undertake a competitive examination to match with their medical specialty and city of practice. Students are then full-time physicians practising under supervision and will be called "doctors" only when graduating at the end of their residency.
After 9 years (or 3 cycles including successfully defending a Practical (or Exercise) thesis (Le Doctorat en Medecine) on an area of interest), they are awarded : Diplôme d'État de docteur en médecine (State diploma of Doctor of Medicine) and Diplôme d'études spécialisées (DES) which are both needed for full registration on the National Council of the Order of Physicians (l'Ordre des médecins) and can practise medicine
=== Ghana ===
All Ghanaian medical schools award an MBChB as the basic medical degree after 6 academic years. These seven medical schools are Kwame Nkrumah University of Science and Technology, University of Ghana, University for Development Studies, University of Cape Coast, University of Health and Allied Sciences and the private Accra College of Medicine, and Family Health Medical School, another private medical school.
=== Guyana ===
The University of Guyana awards MB BS. Other "offshore" United-States-linked schools in the country award the North American MD, such as Texila American University, Lincoln American University.
=== Hong Kong ===
The awarding of qualifications in Hong Kong follows the British tradition.
The dual degree is awarded as:
MBBS at the University of Hong Kong
MBChB at the Chinese University of Hong Kong
=== India ===
In India the MBBS is generally a 5+1⁄2-year course including one year of mandatory internship and an additional year of mandatory rural posting. Some institutes like the All India Institutes of Medical Sciences and other Deemed Medical Colleges do not have the 1 year of mandatory rural posting. During internship, medical students are paid a stipend. Registration as MBBS doctor is granted after completion of these postings. MBBS in India comes under purview of the National Medical Commission which has the power to recognize or de-recognize medical colleges which provide MBBS education.
Over the last decade, a number of medical colleges have been opened in India, to cater to the huge Indian population. The National Medical Commission mentions 704 medical colleges, which teach MBBS in the country, as in July 2023. There are both government run as well as private medical colleges in India. Admission to MBBS program in government colleges can be highly competitive because of subsidized education and extensive hands-on experience. Every year, millions of students appear for the national competitive examination National Eligibility cum Entrance Test (Undergraduate) for a total of 107,798 MBBS seats in the country, as of July 2023.
The MBBS course starts with the basic pre and para-clinical subjects such as biochemistry, physiology, anatomy, microbiology, pathology, forensic medicine including toxicology and pharmacology. The students simultaneously obtain hands-on training in the wards and out-patient departments, where they interact with real patients for five years. The curriculum aims to inculcate standard protocols of history taking, examination, differential diagnosis and complete patient Management. The student is taught to determine what investigations will be useful for a patient and what are the best treatment options. The curriculum also contains a thorough practical knowledge and practice of performing standard clinical procedures. The course also contains a 12-month-long internship, in which an intern is rotated across various specialties. Besides standard clinical care, one also gets a thorough experience of ward management, staff management, and thorough counselling skills. After 1 year of rotatory internship, additional years of rural internship is mandatory in many states, which can be skipped by paying a huge fine to the government, for obtaining permanent registration as a medical practitioner.
MBBS curriculum in India is going through changes with incorporation of modern teaching methods and introduction of National Exit Test (NExT) as the exit test for obtaining MBBS degree, notified on 30 June 2023.
=== Indonesia ===
In Indonesia, graduating students are awarded the academic degree of Sarjana Kedokteran / Bachelor of Medicine (written as suffix "S.Ked") after completing their pre-clinical studies. At this point, the graduate is not yet a practising doctor, but may choose to work directly as a medical scientist or other non-clinician professions (usually health-related). However, most graduates will pursue the conventional path, which is to enroll in the clinical clerkship program (Program Pendidikan Profesi Dokter) for another 1.5 to 2 years. During this program, students are required to rotate through different medical/surgical specialties in a teaching hospital, actively involved in diagnoses and treatment of patients under the direct supervision of residents and consultants/attending physicians. After completing a clinical clerkship, students take the national medical licensing examination (Ujian Kompetensi Mahasiswa Program Profesi Dokter/UKMPPD) and will be awarded the title Dokter (written as prefix "dr.") as their first professional title if they pass the examination.
=== Iraq ===
All medical schools in Iraq award MB ChB, with the exception of the University of Kurdistan-Hewlêr which awards the MBBS degree.
=== Ireland ===
The medical schools in both the Republic of Ireland and Northern Ireland – Queen's University Belfast, Trinity College Dublin, some constituent institutions of the National University of Ireland (University College Dublin, University College Cork and University of Galway), and the Royal College of Surgeons in Ireland — award the degrees of MB BCh BAO. The letters BAO stand for Baccalaureus in Arte Obstetricia (Bachelor of Obstetrics), a degree unique to Ireland which the Irish universities added in the 19th century as the legislation at the time insisted on a final examination in obstetrics. This third degree is not registerable with the Irish Medical Council nor the British General Medical Council (GMC). The only exception is the newly established University of Limerick graduate entry school of medicine which awards BM BS for Bachelor of Medicine and Bachelor of Surgery.
At Trinity College Dublin, the preclinical course leads to an additional Bachelor of Arts (BA) degree (upgradable after three or four years to Master of Arts); as originally after this most students used to go elsewhere to complete clinical training.
LRCPI LRCSI, or simply LRCP&SI, denotes a holder of the historical non-university qualifying licentiates awarded jointly by the Royal College of Physicians of Ireland and the Royal College of Surgeons in Ireland to students of the RCSI's medical school under the Irish Conjoint Scheme. Unlike the corresponding licentiates awarded by the Royal Colleges in Scotland and England (which were external qualifications), these qualifications are still registerable with the Irish Medical Council, but not with the British GMC. Students at RCSI still receive these licences but now also receive the degrees MB BCh BAO, due to RCSI's status as a recognised college of the National University of Ireland. The RCSI students received a Licence in Midwifery (LM) from each college, in the same way that the Irish universities granted BAO degrees, so their qualifications were sometimes expressed as L & LM, RCPI, L & LM, RCSI or more misleadingly as LLM, LRCPI LRCSI, or simply LRCP&SI.
LAH formerly denoted a licentiate of the Apothecaries' Hall of Ireland, and is no longer awarded.
=== Japan ===
In Japan, medical undergraduates are awarded a Bachelor of Medicine, a course of study lasting six years. It is awarded by 42 national, 8 public and 31 private universities.
=== Jordan ===
The Bachelor of Medicine and Surgery (MBBS) degree is awarded in Jordan.
=== Kenya ===
The national universities with medical faculties in Kenya, namely Jomo Kenyatta University of Agriculture and Technology, University of Nairobi, Aga Khan University, Moi University, Kenyatta University, Egerton University, Maseno University and Kenya Methodist University award MB ChB.
Mount Kenya University and Egerton University also award the four-year BSc. Clinical Medicine degree in addition to the six-year MBChB.
=== Liberia ===
The AM. Dogliotti College of Medicine (University of Libeira) awards the MD degree.
=== Libya ===
There are three major public medical universities in Libya, University of Tripoli (Tripoli), University of Benghazi (formerly Garyounis) (Benghazi), and University of Alzaweyah. The schools award the MBBCh.
The Libyan International Medical University is an accredited private medical university that awards an MBChB to its graduates.
=== Malaysia ===
The MBBS is awarded by five public and 17 private universities.
=== Mexico ===
In Mexico, the National Autonomous University of Mexico, the Monterrey Institute of Technology and Higher Education, the National Polytechnic Institute, the Metropolitan Autonomous University, among others, grant the title of "Médico cirujano" (Physician-surgeon) after five or six years of post-high school education, plus one year of internship and one year of social service depending on each institution.
=== Myanmar ===
All five medical schools (UM1, UM 2, DSMA, UMM, UMMG) in Myanmar award the MB BS.
=== Namibia ===
The University of Namibia UNAM School of Medicine, the only medical school in the country, awards the MBChB degree.
=== Nepal ===
There are 18 medical schools in Nepal that award the MBBS degree. Medical education commission, Nepal (MEC) organizes the work related to establishment and operation of medical institutions all over Nepal and bears the sole responsibility to maintain quality, professionalism, institutional accountability and social justice in medical education. There is another entity called Nepal Medical Council (NMC) which major functions are quality control of medical education of the country, establish ethical health care practice, establish standardization of medical practice as well as responsible for giving license to practise medicine within the country's border.
=== Netherlands ===
In the Netherlands, students follow a period of 6 academic years. After three years, students obtain the title Bachelor Geneeskunde (translates to Bachelor of Medicine). After a further three years of study and internships, students obtain the Master Geneeskunde (translates to Master of Medicine) title. After the completion of the master's degree, the students are recognized as medical doctors.
=== New Zealand ===
The two New Zealand medical schools, Auckland and Otago, style their degrees as "MBChB" and "MB ChB" respectively.
=== Nigeria ===
The MBBS/MB ChB is awarded by many public and private universities in Nigeria, after a period of 6 academic years.
=== Pakistan ===
In Pakistan, a medical school is more often referred to as a medical college. The full-form of MBBS is Bachelor of Medicine, Bachelor of Surgery. It is a 5-year course plus one-year internship in affiliated hospital that can be completed from a college recognized by the Pakistan Medical and Dental Council, to receive a degree titled MBBS (Medical colleges in Pakistan). Medical colleges may also teach Post Graduate courses such as FCPS and diplomas. A medical college is affiliated with a university as a department which usually has a separate campus. Currently, a total of 127 medical colleges are listed in World Directory of Medical Schools in Pakistan.
All medical colleges and universities are regulated by the respective provincial department of health. They, however, have to be recognised after meeting criteria set by a central regulatory authority called Pakistan Medical and Dental Council (PMDC). Entrance into the medical colleges is based on merit under the guidelines of PMDC. Both the academic performance at the HSSC (grades 11–12) and a centralized entrance test like NMDCAT, are taken into consideration for the eligibility to enter most of the medical colleges.
To get admission into any government medical college, the weightage is determined by the provincial or federal government. In order to get admission into any private medical college, the following weightage is used:
50% to Marks of entrance test like Medical and Dental College Admission Test (MDCAT).
40% to Marks of Higher Secondary School Certificate (HSSC) Pre-Medical.
10% to Marks of Secondary School Certificate (SSC) Pre-Medical.
=== Rwanda ===
All Rwandan medical schools, public and private, award an MBBS as the basic medical degree after completion of five or six academic years.
=== Saudi Arabia ===
Medical schools in Saudi Arabia award the MBBS.
=== Singapore ===
The Yong Loo Lin School of Medicine at the National University of Singapore and the Lee Kong Chian School of Medicine at Nanyang Technological University confer MB BS. The American Duke University has a medical programme based in Singapore (Duke-NUS Graduate Medical School), but it follows the North American model of styling its degree Doctor of Medicine (MD) at master's degree level.
=== Somalia ===
Somali National University, Amoud University, Benadir University Salaam University and Hargeisa University award the MB ChB, East Africa University awards MMBS.
=== South Africa ===
The University of Pretoria, University of Cape Town, University of the Free State, University of Stellenbosch, University of KwaZulu-Natal, Walter Sisulu University and MEDUNSA all award MBChB, whereas the University of the Witwatersrand styles its degree as MBBCh.
=== South Sudan ===
The University of Juba, University of Bahr El-Ghazal and Upper Nile University in South Sudan awards the MBBS degree after the successful completion of six academic years.
=== Sri Lanka ===
In 1942, the University of Ceylon was established through legislation and the MBBS degree was recognised for registration of doctors in place of the Licentiate in Medicine and Surgery (LMS).
=== Sudan ===
The medical degree in Sudan is a six-year program that includes both classroom and clinical training. Students who successfully complete the program are awarded the Bachelor of Medicine, Bachelor of Surgery (MBBS) degree, which is recognized internationally.
=== Syria ===
The higher education in Syria provides training to a Diploma, Bachelor, Master, and Doctorate levels (see European Education, Audiovisual and Culture Executive Agency on Higher Education: Syria).
=== Tunisia ===
Medical education in Tunisia is solely administered by the government Ministry of Higher Education and Ministry of Public Health. Students get permitted access to medical studies when succeeding their national baccalauréat exam and obtaining a competitive score that allows them admission to medical schools (usually in the 95% percentile).
The curriculum spans six years, two years of fundamental medicine, followed by three years of clinical medicine, culminating in a final year of internship. Upon the completion of this comprehensive training, students are awarded a certificate equivalent to a bachelor's degree, known as the "Diplome de Fin des Etudes Cliniques en Médecine." Subsequently, a national exam is undertaken, and students are ranked based on their performance. Specialization in medicine then follows, ranging from an additional three years for family medicine to five years for most medical and surgical specialties.
During the initial two years at medical school, students focus on foundational subjects such as physiology, semiology, and the fundamentals of medical examination. From the fourth year onwards, they engage in rotations at teaching hospitals, where they actively participate under the guidance of junior and senior physicians, honing their practical skills. At the conclusion of the fifth year, students undergo a competitive examination to determine their medical specialty and city of practice. Following this, they transition to full-time physicians, practising under supervision, and earn the title of "doctors" upon successful completion of their residency.
=== Uganda ===
The nine universities in Uganda that have medical schools that teach undergraduate courses, namely; Makerere University, Mbarara University, Gulu University, Kampala International University, Busitema University, Kabale University, Habib Medical School, St. Augustine International University, and Uganda Christian University all award the MBChB degree, after five years of study.
=== Ukraine ===
In Ukraine, the full-form of MBBS is Bachelor of Medicine and Bachelor of Surgery. It is generally a 5.8 year course including one year compulsory internship, that can be completed from a college accredited by the National Medical Commission. At present, Ukraine is ranked at the fourth position in Europe for having the largest number of post graduates in fields of medicine. Ukraine has a number of Top Government Medical Universities offering MBBS, MD and other degrees in medicine to the local students as well as international students.
The MBBS course starts with the basic pre and para-clinical subjects such as biochemistry, physiology, anatomy, microbiology, pathology, forensic medicine including toxicology and pharmacology. The students simultaneously obtain hands-on training in the wards and out-patient departments, where they interact with real patients for six years. The curriculum aims to inculcate standard protocols of history taking, examination, differential diagnosis and complete patient Management. The student is taught to determine what investigations will be useful for a patient and what are the best treatment options. The curriculum also contains a thorough practical knowledge and practice of performing standard clinical procedures. The course also contains a 12-month-long internship, in which an intern is rotated across various specialties. Besides standard clinical care, one also gets a thorough experience of ward management, staff management, and thorough counselling skills.
The degree awarded is "Bachelor of Medicine and Bachelor of Surgery". The minimum requirements for the MBBS course are 50% marks in physics, chemistry, biology and English in a student's secondary school examinations and student need to pass National Eligibility cum Entrance Test examination for the admission in Ukraine Universities.
=== United Kingdom ===
==== England, Wales, and Northern Ireland ====
While first degrees in medicine meet the expectations of the descriptor for higher education qualification at "level 7 (the UK master's degree)", these degrees usually retain, for historical reasons, "Bachelor of Medicine, Bachelor of Surgery" and are abbreviated to MBChB or MBBS.
Varied abbreviations are used for these degrees in these areas:
MB ChB is used at the universities of Aston, Anglia Ruskin, Birmingham, Bristol, Buckingham, Lancaster, Leeds, Leicester, Liverpool, Keele, Manchester, Sheffield, Sunderland (in partnership with Keele) and Warwick.
MB BCh is used by the Welsh universities, Cardiff University and Swansea University.
MB, BCh, BAO is used at the Queen's University, Belfast
MB BS is used at all medical schools currently or previously part of the University of London (aka The United Hospitals) (Imperial College School of Medicine, UCL Medical School, King's College London School of Medicine, Barts and The London School of Medicine and St George's, University of London). Other medical schools that also award an "MB BS" are Norwich Medical School, Hull York Medical School, Newcastle University, University of Central Lancashire and Ulster University (which is currently partnered with St George's)
BM BCh is awarded by the University of Oxford.
BM BS is used at the University of Nottingham, University of Exeter, University of Plymouth, University of Southampton, University of Surrey, Kent and Medway Medical School and Brighton and Sussex Medical School (formerly at Peninsula College of Medicine and Dentistry)
BM was previously awarded at the University of Southampton. However, beginning in 2013 students have been awarded BMBS. Although no degree in surgery was formally awarded by Southampton, this degree was equivalent to the MB ChB; students may go on to a career in surgery the same as any other graduates in medicine and surgery.
MB BChir is awarded by the University of Cambridge.
At the universities of Oxford and Cambridge, the preclinical course leads to an additional Bachelor of Arts (BA), degree (upgradable after three or four years to Master of Arts), after which most students used to go elsewhere (but usually to one of the London teaching hospitals) to complete clinical training. They could then take the degrees of their new university: They used to have the options of returning to their old university to take the clinical examinations or taking one of the old non-university qualifying examinations. All students at Oxford and Cambridge now remain in place to take their clinical training.
==== Scotland ====
All medical schools in Scotland (Aberdeen, Dundee, Edinburgh and Glasgow) award MB ChB.
The University of St Andrews School of Medicine awarded MB ChB until the early 1970s, but since the incorporation of its clinical medical school into the University of Dundee, St Andrews now only awards a pre-clinical BSc or BSc (Hons), and students go to a Partner Medical School (Aberdeen, Dundee, Edinburgh, Glasgow, or Manchester), where they are awarded an MB ChB after a further three years' study. There is also a programme for Canadian Citizens and residents whereby they complete 3 years at St. Andrews, then 3 years at Edinburgh and are assisted with applying for residency back in Canada.
Since 2018, a joint initiative coordinated by both the Universities of St Andrews and Dundee, the Scottish Graduate Entry Medicine (ScotGEM) programme, has based its first and second year students at St Andrews, and its third and fourth year students at Dundee. This is Scotland's first graduate entry medical degree programme. The intention is that the students of the inaugural cohort, due to graduate in July 2022, will be conferred a joint MB ChB by both universities – the first to graduate with this professional degree directly from St Andrews in over fifty years.
The Scottish Triple Qualification of LRCPE, LRCSE, LRCPSG (earlier LRCPE, LRCSE, LRFPSG) is an old non-university qualifying examination in medicine and surgery awarded jointly by the Royal College of Physicians of Edinburgh, Royal College of Surgeons of Edinburgh and Royal College of Physicians and Surgeons of Glasgow, previously through a Conjoint Board and from 1994 through the United Examining Board. The UEB was dissolved in 2007. These qualifications are still registrable with the GMC, but permission to award them was withdrawn by the Privy Council of the UK in 1999.
==== Historical Primary Medical Qualifications ====
The Conjoint diplomas LRCP MRCS LMSSA were non-university qualifying examinations in medicine and surgery awarded jointly by the Royal College of Physicians of London, Royal College of Surgeons of England and Society of Apothecaries through the United Examining Board from 1994 until 1999, when the General Medical Council withdrew permission. Before 1994, the English Conjoint diploma of LRCP, MRCS was awarded for 110 years, and the LMSSA was a distinct and sometimes less-esteemed qualification. These diplomas slowly became less popular among British medical students, but as recently as 1938 only a half of them qualified with university degrees. The diplomas came to be taken mostly by those who had already qualified in medicine overseas or who failed their medical school finals.
=== United States ===
International medical graduates with an MBBS from foreign countries are generally exempt from having to attend medical school in the United States, but must still undergo US residency and pass the United States Medical Licensing Examination (USMLE), which is given in three exams. The MBBS is not offered at medical schools in the United States as the majority of medical school programs are graduate entry and by tradition offer the MD degree as a primary medical qualification.
There are a number of institutions in the United States that offer a combined 6-year BS-MD joint degree, notably Northeast Ohio Medical University whereby graduating high school seniors complete an accelerated bachelor's degree in two years followed by an MD at the traditional four-year pace. Although the BS-MD pathway is a hybrid undergraduate/graduate program, the result is a primary medical qualification equivalent to an MBBS degree and graduates of these schools go on to enter their intern year at roughly the same age as their UK counterparts. Most American schools offering a BS-MD program do so in 7 years, such as the Indiana University School of Medicine, or in 8 years, such as the Baylor College of Medicine. The Association of American Medical Colleges maintains a list of such schools.
Primarily US-educated MDs and Doctors of Osteopathic Medicine (DOs) go through four years of undergraduate education and apply to professional medical graduate schools with a competitive Medical College Admission Test score and GPA. They then go through two more years of didactic medical science study, and take the pass-fail USMLE Step 1 exam. DO students take a similar exam known as COMLEX Level 1. Following a pass, they then undergo experiential learning of medicine by taking part in patient care in clinics and hospitals under the close supervision of board-certified physicians. After this year, they take the Step 2 Clinical Knowledge exam and formerly took the Step 2 Clinical Skills exam as well. DO students take the COMLEX Level 2-Cognitive Evaulation exam and previously took the COMLEX Level 2-Performance Evaluation exam. COMLEX 2-PE and Step 2 CS were discontinued in 2021 during the COVID-19 pandemic. They then go through one more year of experiential learning, often with elective rotations tailored to particular interests of study or future specialization. They also apply for the National Resident Matching Program in this year. Following their fourth and final year, they graduate from medical school and are awarded their MD or DO degree. If selected for a residency, they continue for a minimum of three to eight years in their specialty where they are officially licensed to practise after completion. New resident physicians, or interns, in the first year of residency, known as intern year or internship, often take the USMLE Step 3 exam or COMLEX Level 3 exam during that year.
Undergraduate students applying to medical school also have the option to apply to an MD/PhD Medical Scientist Training Program at various academic institutions, which entails 7–8 years of primary medical education that is combined with a doctoral thesis. MD/PhD students are required to take all USMLE exams and postgraduate residency training if they wish to practise medicine. A few schools, such as Ohio University's Heritage College of Osteopathic Medicine or the Michigan State University College of Osteopathic Medicine, offer DO/PhD programs.
Most MBBS physicians visiting or practising in the United States use the designation of MD for various personal and professional reasons, but laws may change to require full disclosure when presenting as a clinical practitioner for litigious reasons. The MD title is distinctly used in the US for physicians who earned their medical degree in the US who practise evidence-based medicine. They separate themselves from DOs who go through a different type of education and training that focuses on the patient as a whole and an array of treatments inclusive of medicine and surgery as well.
=== Vietnam ===
There are many medical schools in Vietnam, such as Hanoi Medical University, Vietnam University of Traditional Medicine, and Hue University of Medicine and Pharmacy. Most of them require six years to receive a Doctor of Medicine degree.
=== West Indies ===
All constituent countries of the University of the West Indies (UWI) confer MB BS, due to the historical affiliation of UWI to the University of London. The degree is a 5-year programme. The three physical campuses are Mona in Jamaica, Saint Augustine in Trinidad and Tobago, and Cave Hill in Barbados, with each campus having a Medical Faculty.
The University of Guyana (UG) also confers "MB BS" to their medical school graduates. There are other medical schools in the West Indies, but these follow the North-American system leading to MD.
=== Zambia ===
All schools in Zambia award the MBChB degree.
=== Zimbabwe ===
The University of Zimbabwe College of Health Sciences (UZ-CHS) awards the MBChB degree. Midlands State University (MSU) also offers the MBChB degree. The National University of Science and Technology (NUST) awards the MBBS.
== Classification ==
Medical degrees differ from other undergraduate degrees in that they are professional qualifications that lead holders to enter a particular career upon receipt. This is not the case with most other undergraduate degrees, so whilst the Bachelor of Medicine and Bachelor of Surgery are undergraduate or graduate degrees (depending on the institution), they are perhaps more accurately conceptualised as a so-called first professional degree. Other professions whose qualifications follow a similar pattern include:
Dentistry
Education
Engineering
Environmental Health
Medical Laboratory Science
Occupational Therapy
Optometry
Pharmacy
Physical Therapy
Clinical Psychology
Law
Veterinary Medicine
Osteopathy
Physician Assistant
Nursing
OT Technician
Bachelor of Medicine, Bachelor of Surgery are usually awarded as professional degrees, not as honours degrees, and as such the graduate is not classified as for honours degrees in other subjects. However, at many institutions (for example the University of Aberdeen, University of Birmingham, University of Sheffield, University of Liverpool, University of Leicester, Hull York Medical School, and University of Manchester in England, Queen's University Belfast in Northern Ireland, Cardiff University in Wales and the University of Dundee in Scotland), it is possible for the degrees to be awarded with Honours (i.e. MB ChB (Hons.)) or with Commendation, if the board of examiners recognises exceptional performance throughout the degree course. Very few of these are awarded.
More often, it is possible to study one subject for an extra year for an intercalated honours degree. This is usually a Bachelor of Science (BSc), Bachelor of Medical Science (BMedSci), Bachelor of Medical Biology (BMedBiol) or similar: at Oxford and Cambridge in England and Dublin in Ireland Bachelor of Arts degrees are awarded. At a few universities most medical students obtain an ordinary degree in science as well: when the University of Edinburgh had a six-year course, the third year was followed by the award of an ordinary BSc(MedSci). In Australia, The University of Melbourne in Australia offers an Arts Degree (BA) to a medical student on the completion of two extra years of undergraduate study, and Monash University offers a law degree (LLB); if the optional law degree is undertaken, on completion of their degree the student may choose to do a one-year internship at a hospital and become a doctor, or spend one year doing articles to practise thereafter as a lawyer. At the University of Nottingham and the University of Southampton, both in England, all medical students on the five-year course obtain a Bachelor of Medical Sciences (BMedSci) degree without an extra intercalated year. At the University of Cambridge, Imperial College London and University College London, certain medical students are able to extend their intercalated year to an extra three years, thus temporarily exiting the MBBS course to complete a PhD. Upon completion of the PhD, the student is required to sit the remaining 2 years of the medicine course to receive his/her MBBS degree. The University of the West Indies, Mona in Kingston, Jamaica automatically awards a Bachelor of Medical Sciences (BMedSci) degree to all students who have successfully completed three years of their MBBS programme.
== Progression ==
Medical graduates are eligible to sit postgraduate examinations, including examinations for membership and fellowship of professional institutions. Among the latter are the Membership of the Royal College of Surgeons, postgraduate master's degrees (such as a Master of Surgery or Master of Medicine), and a postgraduate doctorate in medicine (such as Doctor of Medicine or Doctor of Science, if earned in Ireland, the UK or Commonwealth nations, and board certification examinations).
== See also ==
Bachelor of Ayurveda, Medicine and Surgery
Bachelor of Unani Medicine and Surgery
Bachelor's degree
Doctor of Medicine
Doctor of Osteopathic Medicine
Homologation
List of medical schools
Master of Medicine
Master of Surgery
Medical education
Medical school
Pre-medical
== References == | Wikipedia/Bachelor_of_Medicine_and_Bachelor_of_Surgery |
A doctorate (from Latin doctor, meaning "teacher") or doctoral degree is a postgraduate academic degree awarded by universities and some other educational institutions, derived from the ancient formalism licentia docendi ("licence to teach").
In most countries, a research degree qualifies the holder to teach at university level in the degree's field or work in a specific profession. There are a number of doctoral degrees; the most common is the Doctor of Philosophy (PhD), awarded in many different fields, ranging from the humanities to scientific disciplines.
Many universities also award honorary doctorates to individuals deemed worthy of special recognition, either for scholarly work or other contributions to the university or society.
== History ==
=== Middle Ages ===
The term doctor derives from Latin, meaning "teacher" or "instructor". The doctorate (Latin: doctoratus) appeared in medieval Europe as a license to teach Latin (licentia docendi) at a university. Its roots can be traced to the early church in which the term doctor referred to the Apostles, Church Fathers, and other Christian authorities who taught and interpreted the Bible.
The right to grant a licentia docendi (i.e. the doctorate) was originally reserved to the Catholic Church, which required the applicant to pass a test, take an oath of allegiance, and pay a fee. The Third Council of the Lateran of 1179 guaranteed access—at that time essentially free of charge—to all able applicants. Applicants were tested for aptitude. This right remained a bone of contention between the church authorities and the universities, slowly distancing themselves from the Church. In 1213 the right was granted by the pope to the University of Paris, where it became a universal license to teach (licentia ubique docendi). However, while the licentia continued to hold a higher prestige than the bachelor's degree (baccalaureus), the latter was ultimately reduced to an intermediate step to the master's degree (magister) and doctorate, both of which now became the accepted teaching qualifications. According to Keith Allan Noble (1994), the first doctoral degree was awarded in medieval Paris around 1150 by the University of Paris.
George Makdisi theorizes that the ijazah issued in early Islamic madrasahs was the origin of the doctorate later issued in medieval European universities. Alfred Guillaume and Syed Farid al-Attas agree that there is a resemblance between the ijazah and the licentia docendi. However, Toby Huff and others reject Makdisi's theory. Devin J. Stewart notes a difference in the granting authority (individual professor for the ijzazah and a corporate entity in the case of the university doctorate).
=== 17th and 18th centuries ===
The doctorate of philosophy developed in Germany in the 17th century (likely c. 1652). The term "philosophy" does not refer here to the field or academic discipline of philosophy; it is used in a broader sense under its original Greek meaning of "love of wisdom". In most of Europe, all fields (history, philosophy, social sciences, mathematics, and natural philosophy/natural sciences) were traditionally known as philosophy, and in Germany and elsewhere in Europe the basic faculty of liberal arts was known as the "faculty of philosophy". The Doctorate of Philosophy adheres to this historic convention, even though most degrees are not for the study of philosophy. Chris Park explains that it was not until formal education and degree programs were standardized in the early 19th century that the Doctorate of Philosophy was reintroduced in Germany as a research degree, abbreviated as Dr. phil. (similar to Ph.D. in Anglo-American countries). Germany, however, differentiated then in more detail between doctorates in philosophy and doctorates in the natural sciences, abbreviated as Dr. rer. nat. and also doctorates in the social/political sciences, abbreviated as Dr. rer. pol., similar to the other traditional doctorates in medicine (Dr. med.) and law (Dr. jur.).
University doctoral training was a form of apprenticeship to a guild. The traditional term of study before new teachers were admitted to the guild of "Masters of Arts" was seven years, matching the apprenticeship term for other occupations. Originally the terms "master" and "doctor" were synonymous, but over time the doctorate came to be regarded as a higher qualification than the master's degree.
University degrees, including doctorates, were originally restricted to men. The first women to be granted doctorates were Juliana Morell in 1608 at Lyons or maybe Avignon (she "defended theses" in 1606 or 1607, although claims that she received a doctorate in canon law in 1608 have been discredited), Elena Cornaro Piscopia in 1678 at the University of Padua, Laura Bassi in 1732 at Bologna University, Dorothea Erxleben in 1754 at Halle University and María Isidra de Guzmán y de la Cerda in 1785 at Complutense University, Madrid.
=== Modern times ===
The use and meaning of the doctorate have changed over time and are subject to regional variations. For instance, until the early 20th century, few academic staff or professors in English-speaking universities held doctorates, except for very senior scholars and those in holy orders. After that time, the German practice of requiring lecturers to have completed a research doctorate spread. Universities' shift to research-oriented education (based upon the scientific method, inquiry, and observation) increased the doctorate's importance. Today, a research doctorate (PhD) or its equivalent (as defined in the US by the NSF) is generally a prerequisite for an academic career. However, many recipients do not work in academia.
Professional doctorates developed in the United States from the 19th century onward. The first professional doctorate offered in the United States was the MD at Kings College (now Columbia University) after the medical school's founding in 1767. However, this was not a professional doctorate in the modern American sense. It was awarded for further study after the qualifying Bachelor of Medicine (MB) rather than a qualifying degree. The MD became the standard first degree in medicine in the US during the 19th century, but as a three-year undergraduate degree. It did not become established as a graduate degree until 1930. As the standard qualifying degree in medicine, the MD gave that profession the ability (through the American Medical Association, established in 1847 for this purpose) to set and raise standards for entry into professional practice.In the shape of the German-style PhD, the modern research degree was first awarded in the US in 1861, at Yale University. This differed from the MD in that the latter was a vocational "professional degree" that trained students to apply or practice knowledge rather than generate it, similar to other students in vocational schools or institutes. In the UK, research doctorates initially took higher doctorates in Science and Letters, first introduced at Durham University in 1882. The PhD spread to the UK from the US via Canada and was instituted at all British universities from 1917. The first (titled a DPhil) was awarded at the University of Oxford.
Following the MD, the next professional doctorate in the US, the Juris Doctor (JD), was established by the University of Chicago in 1902. However, it took a long time to be accepted, not replacing the Bachelor of Laws (LLB) until the 1960s, by which time the LLB was generally taken as a graduate degree. Notably, the JD and LLB curriculum were identical, with the degree being renamed as a doctorate, and it (like the MD) was not equivalent to the PhD, raising criticism that it was "not a 'true Doctorate'". When professional doctorates were established in the UK in the late 1980s and early 1990s, they did not follow the US model. Still, they were set up as research degrees at the same level as PhDs but with some taught components and a professional focus for research work.
Now usually called higher doctorates in the United Kingdom, the older-style doctorates take much longer to complete since candidates must show themselves to be leading experts in their subjects. These doctorates are less common than the PhD in some countries and are often awarded honoris causa. The habilitation is still used for academic recruitment purposes in many countries within the EU. It involves either a long new thesis (a second book) or a portfolio of research publications. The habilitation (highest available degree) demonstrates independent and thorough research, experience in teaching and lecturing, and, more recently, the ability to generate supportive funding. The habilitation follows the research doctorate, and in Germany, it can be a requirement for appointment as a Privatdozent or professor.
== Types ==
Since the Middle Ages, the number and types of doctorates awarded by universities have proliferated throughout the world. Practice varies from one country to another. While a doctorate usually entitles a person to be addressed as "doctor", the use of the title varies widely depending on the type and the associated occupation.
=== Research doctorate ===
Research doctorates are awarded in recognition of publishable academic research, at least in principle, in a peer-reviewed academic journal. The best-known research degree in the English-speaking world is the Doctor of Philosophy (abbreviated PhD or, at a small number of British universities, DPhil) awarded in many countries throughout the world. In the US, for instance, although the most typical research doctorate is the PhD, accounting for about 98% of the research doctorates awarded, there are more than 15 other names for research doctorates. Other research-oriented doctorates (some having a professional practice focus) include the Doctor of Education (EdD), the Doctor of Science (DSc or ScD),Doctor of Arts (DA), Doctor of Juridical Science (JSD or SJD), Doctor of Musical Arts (DMA), Doctor of Professional Studies/Professional Doctorate (ProfDoc or DProf), Doctor of Public Health (DrPH), Doctor of Social Science (DSSc or DSocSci), Doctor of Management (DM, DMan or DMgt), Doctor of Business Administration (DBA), Doctor of Engineering (DEng, DESc, DES or EngD) the German engineering doctorate Doktoringenieur (Dr.-Ing.), natural science doctorate Doctor rerum naturalium (Dr. rer. nat.), and economics and social science doctorate Doctor rerum politicarum (Dr. rer. pol.). The UK Doctor of Medicine (MD or MD (Res)) and Doctor of Dental Surgery (DDS) are research doctorates. The Doctor of Theology (ThD or DTh), Doctor of Practical Theology (DPT) and the Doctor of Sacred Theology (STD, or DSTh) are research doctorates in theology.
Criteria for research doctorates vary but typically require completion of a substantial body of original research, which may be presented as a single thesis or dissertation, or as a portfolio of shorter project reports (thesis by publication). The submitted dissertation is assessed by a committee of, typically, internal, and external examiners. It is then typically defended by the candidate during an oral examination (called viva (voce) in the UK and India) by the committee, which then awards the degree unconditionally, awards the degree conditionally (ranging from corrections in grammar to additional research), or denies the degree. Candidates may also be required to complete graduate-level courses in their field and study research methodology.
Criteria for admission to doctoral programs vary. Students may be admitted with a bachelor's degree in the US and the UK However, elsewhere, e.g. in Finland and many other European countries, a master's degree is required. The time required to complete a research doctorate varies from three years, excluding undergraduate study, to six years or more.
=== Licentiate ===
Licentiate degrees vary widely in their meaning, and in a few countries are doctoral-level qualifications. Sweden awards the licentiate degree as a two-year qualification at the doctoral level and the doctoral degree (PhD) as a four-year qualification. Sweden originally abolished the Licentiate in 1969 but reintroduced it in response to demands from business. Finland also has a two-year doctoral level licentiate degree, similar to Sweden's. Outside of Scandinavia, the licentiate is usually a lower-level qualification. In Belgium, the licentiate was the basic university degree prior to the Bologna Process and was equivalent to a bachelor's degree. In France and other countries, it is the bachelor's-level qualification in the Bologna process. In the Pontifical system, the Licentiate in Sacred Theology (STL) is equivalent to an advanced master's degree, or the post-master's coursework required in preparation for a doctorate (i.e. similar in level to the Swedish/Finnish licentiate degree). While other licences (such as the Licence in Canon Law) are at the level of master's degrees.
=== Higher doctorate and post-doctoral degrees ===
A higher tier of research doctorates may be awarded based on a formally submitted portfolio of published research of an exceptionally high standard. Examples include the Doctor of Science (DSc or ScD), Doctor of Divinity (DD), Doctor of Letters (DLitt or LittD), Doctor of Law or Laws (LLD), and Doctor of Civil Law (DCL) degrees found in the UK, Ireland and some Commonwealth countries, and the traditional doctorates in Scandinavia like the Doctor Medicinae (Dr. Med.).
The habilitation teaching qualification (facultas docendi or "faculty to teach") under a university procedure with a thesis and an exam is commonly regarded as belonging to this category in Germany, Austria, France, Liechtenstein, Switzerland, Poland, etc. The degree developed in Germany in the 19th century "when holding a doctorate seemed no longer sufficient to guarantee a proficient transfer of knowledge to the next generation". In many federal states of Germany, the habilitation results in an award of a formal "Dr. habil." degree or the holder of the degree may add "habil." to their research doctorate such as "Dr. phil. habil." or "Dr. rer. nat. habil." In some European universities, especially in German-speaking countries, the degree is insufficient to have teaching duties without professor supervision (or teaching and supervising PhD students independently) without an additional teaching title such as Privatdozent. In Austria, the habilitation bestows the graduate with the facultas docendi, venia legendi. Since 2004, the honorary title of "Privatdozent" (before this, completing the habilitation resulted in appointment as a civil servant). In many Central and Eastern Europe countries, the degree gives venia legendi, Latin for "the permission to lecture", or ius docendi, "the right to teach", a specific academic subject at universities for a lifetime. The French academic system used to have a higher doctorate, called the "state doctorate" (doctorat d'État), but, in 1984, it was superseded by the habilitation (Habilitation à diriger des recherches, "habilitation to supervise (doctoral and post-doctoral) research", abbreviated HDR) which is the prerequisite to supervise PhDs and to apply to Full Professorships. In many countries of the previous Soviet Union (USSR), for example the Russian Federation or Ukraine there is the higher doctorate (above the title of "Candidate of Sciences"/PhD) under the title "Doctor of Sciences".
While this section has focused on earned qualifications conferred in virtue of published work or the equivalent, a higher doctorate may also be presented on an honorary basis by a university — at its own initiative or after a nomination — in recognition of public prestige, institutional service, philanthropy, or professional achievement. In a formal listing of qualifications, and often in other contexts, an honorary higher doctorate will be identified using language like "DCL, honoris causa", "Hon LLD", or "LittD h.c.".
=== Professional doctorate ===
Depending on the country, professional doctorates may also be research degrees at the same level as PhDs. The relationship between research and practice is considered important and professional degrees with little or no research content are typically aimed at professional performance. Many professional doctorates are named "Doctor of [subject name] and abbreviated using the form "D[subject abbreviation]" or "[subject abbreviation]D", or may use the more generic titles "Professional Doctorate", abbreviated "ProfDoc" or "DProf", "Doctor of Professional Studies" (DPS) or "Doctor of Professional Practice" (DPP).
In the US, professional doctorates (formally "doctor's degree – professional practice" in government classifications) are defined by the US Department of Education's National Center for Educational Statistics as degrees that require a minimum of six years of university-level study (including any pre-professional bachelor's or associate degree) and meet the academic requirements for professional licensure in the discipline. The definition for a professional doctorate does not include a requirement for either a dissertation or study beyond master's level, in contrast to the definition for research doctorates ("doctor's degree – research/scholarship"). However, individual programs may have different requirements. There is also a category of "doctor's degree – other" for doctorates that do not fall into either the "professional practice" or "research/scholarship" categories. All of these are considered doctoral degrees.
In contrast to the US, many countries reserve the term "doctorate" for research degrees. If, as in Canada and Australia, professional degrees bear the name "Doctor of ...", etc., it is made clear that these are not doctorates. Examples of this include Doctor of Pharmacy (PharmD), Doctor of Medicine (MD), Doctor of Dental Surgery (DDS), Doctor of Nursing Practice (DNP), and Juris Doctor (JD). Contrariwise, for example, research doctorates like Doctor of Business Administration (DBA), Doctor of Education (EdD) and Doctor of Social Science (DSS) qualify as full academic doctorates in Canada though they normally incorporate aspects of professional practice in addition to a full dissertation. In the Philippines, the University of the Philippines Open University offers a Doctor of Communication (DComm) professional doctorate.
All doctorates in the UK and Ireland are third cycle qualifications in the Bologna Process, comparable to US research doctorates. Although all doctorates are research degrees, professional doctorates normally include taught components, while the name PhD/DPhil is normally used for doctorates purely by thesis. Professional, practitioner, or practice-based doctorates such as the DClinPsy, MD, DHSc, EdD, DBA, EngD and DAg are full academic doctorates. They are at the same level as the PhD in the national qualifications frameworks; they are not first professional degrees but are "often post-experience qualifications" in which practice is considered important in the research context. In 2009 there were 308 professional doctorate programs in the UK, up from 109 in 1998, with the most popular being the EdD (38 institutions), DBA (33), EngD/DEng (22), MD/DM (21), and DClinPsy/DClinPsych/ClinPsyD (17). Similarly, in Australia, the term "professional doctorate" is sometimes applied to the Scientiae Juridicae Doctor (SJD), which, like the UK professional doctorates, is a research degree.
=== Honorary doctorate ===
When a university wishes to formally recognize an individual's contributions to a particular field or philanthropic efforts, it may choose to grant a doctoral degree honoris causa ('for the sake of the honor'), waiving the usual requirements for granting the degree. Some universities do not award honorary degrees, for example, Cornell University, the University of Virginia, and Massachusetts Institute of Technology.
== National variations ==
=== Argentina ===
In Argentina the doctorate (doctorado) is the highest academic degree. The intention is that candidates produce original contributions in their field knowledge within a frame of academic excellence. A dissertation or thesis is prepared under the supervision of a tutor or director. It is reviewed by a Doctoral Committee composed of examiners external to the program and at least one examiner external to the institution. The degree is conferred after a successful dissertation defence. In 2006, there were approximately 2,151 postgraduate careers in the country, of which 14% were doctoral degrees. Doctoral programs in Argentina are overseen by the National Commission for University Evaluation and Accreditation, an agency in Argentina's Ministry of Education, Science and Technology.
=== Australia ===
The Australian Qualifications Framework (AQF) categorizes tertiary qualifications into ten levels that are numbered from one to ten in ascending order of complexity and depth. Of these qualification levels, six are for higher education qualifications and are numbered from five to ten. Doctoral degrees occupy the highest of these levels: level ten.: 63 All doctoral degrees involve research and this is a defining characteristic of them.: 63 There are three categories of doctoral degrees recognized by the AQF: research doctorates, professional doctorates and higher doctorates.: 63–64
Research doctorates and professional doctorates are both completed as part of a programme of study and supervised research.: 63 Both have entry requirements of the student having a supervisor that has agreed to supervise their research, along with the student possessing an honours degree with upper second-class honours or better or a master's degree with a substantial research component. Research doctorates are typically titled Doctor of Philosophy and they are awarded on the basis of an original and significant contribution to knowledge.: 63 Professional doctorates are typically titled Doctor of (field of study) and they are awarded on the basis of an original and significant contribution to professional practice.: 63
Higher doctorates are typically titled similarly to professional doctorates and are awarded based on a submitted portfolio of research that follows a consistent theme and is internationally recognized as an original and substantive contribution to knowledge beyond that required for the awarding of a research doctorate.: 64 Typically, to be eligible to be awarded a higher doctorate a student must have completed a research doctorate at least seven to ten years prior to submitting the research portfolio used to award them a higher doctorate.
=== Brazil ===
Doctoral candidates are normally required to have a master's degree in a related field. Exceptions are based on their individual academic merit. A second and a third foreign language are other common requirements, although the requirements regarding proficiency commonly are not strict. The admissions process varies by institution. Some require candidates to take tests while others base admissions on a research proposal application and interview only. In both instances however, a faculty member must agree prior to admission to supervise the applicant.
Requirements usually include satisfactory performance in advanced graduate courses, passing an oral qualifying exam and submitting a thesis that must represent an original and relevant contribution to existing knowledge. The thesis is examined in a final public oral exam administered by at least five faculty members, two of whom must be external. After completion, which normally consumes 4 years, the candidate is commonly awarded the degree of Doutor (Doctor) followed by the main area of specialization, e.g. Doutor em Direito (Doctor of Laws), Doutor em Ciências da Computação (Doctor of Computer Sciences), Doutor em Filosofia (Doctor of Philosophy), Doutor em Economia (Doctor of Economics), Doutor em Engenharia (Doctor of Engineering) or Doutor em Medicina (Doctor of Medicine). The generic title of Doutor em Ciências (Doctor of Sciences) is normally used to refer collectively to doctorates in the natural sciences (i.e. Physics, Chemistry, Biological and Life Sciences, etc.)
All graduate programs in Brazilian public universities are tuition-free (mandated by the Brazilian constitution). Some graduate students are additionally supported by institutional scholarships granted by federal government agencies like CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and CAPES (Coordenação de Aperfeiçoamento do Pessoal de Ensino Superior). Personal scholarships are provided by the various FAP's (Fundações de Amparo à Pesquisa) at the state level, especially FAPESP in the state of São Paulo, FAPERJ in the state of Rio de Janeiro and FAPEMIG in the state of Minas Gerais. Competition for graduate financial aid is intense and most scholarships support at most 2 years of Master's studies and 4 years of doctoral studies. The normal monthly stipend for doctoral students in Brazil is between US$500 and $1000.
A degree of Doutor usually enables an individual to apply for a junior faculty position equivalent to a US assistant professor. Progression to full professorship, known as Professor Titular requires that the candidate be successful in a competitive public exam and normally takes additional years. In the federal university system, doctors who are admitted as junior faculty members may progress (usually by seniority) to the rank of associate professor, then become eligible to take the competitive exam for vacant full professorships. In São Paulo state universities, associate professorships and subsequent eligibility to apply for a full professorship are conditioned on the qualification of Livre-docente and requires, in addition to a doctorate, a second thesis or cumulative portfolio of peer-reviewed publications, a public lecture before a panel of experts (including external members from other universities), and a written exam.
In recent years some initiatives as jointly supervised doctorates (e.g. "cotutelles") have become increasingly common in the country, as part of the country's efforts to open its universities to international students.
=== Denmark ===
Denmark offers two types of "doctorate"-like degrees:
A three-year ph.d. degree program, which replaced the equivalent licentiat in 1992, and does not grant the holder the right to the title dr. or doktor. At the same time, a minor, two-year research training program, leading to a title of "magister", was phased out to meet the international standards of the Bologna Process.
A 'full' doctor's degree (e.g. dr.phil., Doctor Philosophiae, for humanistic and STEM subjects) – the higher doctorate – introduced in 1479. The second part of the title communicates the field of study – e.g. dr.scient (in the sciences), dr.jur (in law), dr.theol (in theology).
For the ph.d. degree, the candidates (ph.d. students or fellows) – who are required to have a master's degree – enroll at a ph.d. school at a university and participate in a research training program, at the end of which they each submit a thesis and defend it orally at a formal disputation. In the disputation, the candidates defend their theses against three official opponents, and may take opponents or questions from those present in the auditorium (ex auditorio).
For the higher doctorate, the candidate (referred to as præses) is required to submit a thesis of major scientific significance, and to proceed to defend it orally against two official opponents, as well as against any and all opponents from the auditorium (ex auditorio) – no matter how long the proceedings take. The official opponents are required to be full professors. The candidate is required to have a master's degree, but not necessarily a ph.d.
The ph.d. was introduced as a separate title from the higher doctorate in 1992 as part of the transition to a new degree structure, since the changes in the degree system would otherwise leave a significant amount of academics without immediately recognizable qualifications in international settings. The original vision was purported to be to phase out the higher doctorate in favor of the ph.d. (or merge the two), but so far, there are no signs of this happening. Many Danish academics with permanent positions wrote ph.d. dissertations in the 90s when the system was new, since at that time, a ph.d. degree or equivalent qualifications began to be required for certain academic positions in Denmark. Until the late 20th century, the higher doctorate was a condition for attaining full professorship; it is no longer required per se for any positions, but is considered amply equivalent to the ph.d. when applying for academic positions.
=== Egypt ===
In Egypt, the highest degree doctorate is awarded by Al-Azhar University est. 970, which grants ( العالمية Ālimiyya\ Habilitation).
The Medical doctorate (abbreviated as M.D.) is equivalent to the Ph.D. degree. To earn an M.D. in a science specialty, one must have a master's degree (M.Sc.) (or two diplomas before the introduction of M.Sc. degree in Egypt) before applying. The M.D. degree involves courses in the field and defending a dissertation. It takes on average three to five years.
Many postgraduate medical and surgical specialties students earn a doctorate. After finishing a 6-year medical school and one-year internship (house officer), physicians and surgeons earn the M.B. B.Ch. degree, which is equivalent to a US MD degree. They can then apply to earn a master's degree or a speciality diploma, then an MD degree in a specialty.
The Egyptian M.D. degree is written using the name of one's specialty. For example, M.D. (Geriatrics) means a doctorate in Geriatrics, which is equivalent to a Ph.D. in Geriatrics.
=== Finland ===
The Finnish requirement for the entrance into doctoral studies is a master's degree or equivalent. All universities have the right to award doctorates. The ammattikorkeakoulu institutes (institutes of higher vocational education that are not universities but often called "Universities of Applied Sciences" in English) do not award doctoral or other academic degrees. The student must:
Demonstrate understanding of their field and its meaning, while preparing to use scientific or scholarly study in their field, creating new knowledge.
Obtain a good understanding of development, basic problems and research methods
Obtain such understanding of the general theory of science and letters and such knowledge of neighbouring research fields that they are able to follow the development of these fields.
The way to show that these general requirements have been met is:
Complete graduate coursework.
Demonstrate critical and independent thought
Prepare and publicly defend a dissertation (a monograph or a compilation thesis of peer-reviewed articles). In fine arts, the dissertation may be substituted by works and/or performances as accepted by the faculty.
Entrance to a doctoral program is available only for holders of a master's degree; there is no honors procedure for recruiting Bachelors. Entrance is not as controlled as in undergraduate studies, where a strict numerus clausus is applied. Usually, a prospective student discusses their plans with a professor. If the professor agrees to accept the student, the student applies for admission. The professor may recruit students to their group. Formal acceptance does not imply funding. The student must obtain funding either by working in a research unit or through private scholarships. Funding is more available for natural and engineering sciences than in letters. Sometimes, normal work and research activity are combined.
Prior to introduction of the Bologna process, Finland required at least 42 credit weeks (1,800 hours) of formal coursework. The requirement was removed in 2005, leaving the decision to individual universities, which may delegate the authority to faculties or individual professors. In Engineering and Science, required coursework varies between 40 and 70 ECTS.
The duration of graduate studies varies. It is possible to graduate three years after the master's degree, while much longer periods are not uncommon. The study ends with a dissertation, which must present substantial new scientific/scholarly knowledge. The dissertation can either be a monograph or it an edited collection of 3 to 7 journal articles. Students unable or unwilling to write a dissertation may qualify for a licentiate degree by completing the coursework requirement and writing a shorter thesis, usually summarizing one year of research.
When the dissertation is ready, the faculty names two expert pre-examiners with doctoral degrees from the outside the university. During the pre-examination process, the student may receive comments on the work and respond with modifications. After the pre-examiners approve, the doctoral candidate applies the faculty for permission to print the thesis. When granting this permission, the faculty names the opponent for the thesis defence, who must also be an outside expert, with at least a doctorate. In all Finnish universities, long tradition requires that the printed dissertation hang on a cord by a public university noticeboard for at least ten days prior to for the dissertation defence.
The doctoral dissertation takes place in public. The opponent and the candidate conduct a formal debate, usually wearing white tie, under the supervision of the thesis supervisor. Family, friends, colleagues and the members of the research community customarily attend the defence. After a formal entrance, the candidate begins with an approximately 20-minute popular lecture (lectio praecursoria), that is meant to introduce laymen to the thesis topic. The opponent follows with a short talk on the topic, after which the pair critically discuss the dissertation. The proceedings take two to three hours. At the end the opponent presents their final statement and reveals whether he/she will recommend that the faculty accept it. Any member of the public then has an opportunity to raise questions, although this is rare. Immediately after the defence, the supervisor, the opponent and the candidate drink coffee with the public. Usually, the attendees of the defence are given the printed dissertation. In the evening, the passed candidate hosts a dinner (Finnish: karonkka) in honour of the opponent. Usually, the candidate invites their family, colleagues and collaborators.
Doctoral graduates are often Doctors of Philosophy (filosofian tohtori), but many fields retain their traditional titles: Doctor of Medicine (lääketieteen tohtori), Doctor of Science in technology (tekniikan tohtori), Doctor of Science in arts (Art and Design), etc.
The doctorate is a formal requirement for a docenture or professor's position, although these in practice require postdoctoral research and further experience. Exceptions may be granted by the university governing board, but this is uncommon, and usually due to other work and expertise considered equivalent.
=== France ===
History
Before 1984 three research doctorates existed in France: the State doctorate (doctorat d'État, "DrE", the old doctorate introduced in 1808), the third cycle doctorate (doctorat de troisième cycle, also called doctorate of specialty, doctorat de spécialité, created in 1954 and shorter than the State doctorate) and the diploma of doctor-engineer (diplôme de docteur-ingénieur created in 1923), for technical research.
During the first half of the 20th century, following the submission of two theses (primary thesis, thèse principale, and secondary thesis, thèse complémentaire) to the Faculty of Letters (in France, "letters" is equivalent to "humanities") at the University of Paris, the doctoral candidate was awarded the Doctorat ès lettres. There was also the less prestigious "university doctorate", doctorat d'université, which could be received for the submission of a single thesis.
In the 1950s, the Doctorat ès lettres was renamed to Doctorat d'État. In 1954 (for the sciences) and 1958 (for letters and human sciences), the less demanding doctorat de troisième cycle degree was created on the model of the American Ph.D. with the purpose to lessen what had become an increasingly long period of time between the typical students' completion of their Diplôme d'études supérieures, roughly equivalent to a Master of Arts, and their Doctorat d'État.
After 1984, only one type of doctoral degree remained: the "doctorate" (Doctorat). A special diploma was created called the "Habilitation to Supervise Research" (also translated as "accreditation to supervise research"; Habilitation à diriger des recherches), a professional qualification to supervise doctoral work. (This diploma is similar in spirit to the older State doctorate, and the requirements for obtaining it are similar to those necessary to obtain tenure in other systems.) Before only professors or senior full researchers of similar rank were normally authorized to supervise a doctoral candidate's work. Now habilitation is a prerequisite to the title of professor in university (Professeur des universités) and to the title of Research Director (Directeur de recherche) in national public research agency such as CNRS, INRIA, or INRAE.
Admission
Today, the doctorate (doctorat) is a research-only degree. It is a national degree and its requirements are fixed by the minister of higher education and research. Only public institutions award the doctorate. It can be awarded in any field of study. The master's degree is a prerequisite. The normal duration is three years. The writing of a comprehensive thesis constitutes the bulk of the doctoral work. While the length of the thesis varies according to the discipline, it is rarely less than 150 pages, and often substantially more. Some 15,000 new doctoral matriculations occur every year and ≈10,000 doctorates are awarded.
Doctoral candidates can apply for a three-year fellowship. The most well known is the Contrat Doctoral (4,000 granted every year with a gross salary of 1758 euros per month as of September 2016).
Since 2002, candidates follow in-service training, but there is no written examination for the doctorate. The candidate has to write a thesis that is read by two external reviewers. The head of the institution decides whether the candidate can defend the thesis, after considering the external reviews. The jury members are designated by the head of the institution. The candidate's supervisor and the external reviewers are generally jury members. The maximum number of jury members is 8. The defense generally lasts 45 minutes in scientific fields, followed by 1 – 2+1⁄2 hours of questions from the jury or other doctors present. The defense and questions are public. The jury then deliberates in private and then declares the candidate admitted or "postponed". The latter is rare. New regulations were set in 2016 and do not award distinctions.
The title of doctor (docteur) can also be used by medical and pharmaceutical practitioners who hold a doctor's State diploma (diplôme d'État de docteur, distinct from the doctorat d'État mentioned above). The diploma is a first-degree.
A guideline with good practices and legal analysis has been published in 2018 by the Association nationale des docteurs (ANDès) and the Confédération des Jeunes Chercheurs (CJC) with funding from the French Ministry of research.
=== Germany ===
Doctoral degrees in Germany are research doctorates and are awarded by a process called Promotion. Most doctorates are awarded with specific Latin designations for the field of research (except for engineering, where the designation is German), instead of a general name for all fields (such as the Ph.D.). The most important degrees are:
Dr. theol. (theologiae; theology);
Dr. phil. (philosophiae; humanities such as philosophy, philology, history, and social sciences such as sociology, political science, or psychology as well);
Dr. rer. nat. (rerum naturalium; natural and formal sciences, i.e. physics, chemistry, biology, mathematics, computer science and information technology, or psychology);
Dr. iur. (iuris; law);
Dr. med. (medicinae; medicine);
Dr. med. dent. (medicinae dentariae; dentistry);
Dr. med. vet. (medicinae veterinariae; veterinary medicine);
Dr.-Ing. (engineering);
Dr. oec. (oeconomiae; economics);
Dr. rer. pol. (rerum politicarum; economics, business administration, political science).
The concept of a US-style professional doctorate as an entry-level professional qualification does not exist. Professional doctorates obtained in other countries, not requiring a thesis or not being third cycle qualifications under the Bologna process, can only be used postnominally, e.g., "Max Mustermann, MD", and do not allow the use of the title Dr.
In medicine, "doctoral" dissertations are often written alongside undergraduate study therefore, European Research Council decided in 2010 that such Dr. med. degrees do not meet the international standards of a Ph.D. research degree. The duration of the doctorate depends on the field: a doctorate in medicine may take less than a full-time year to complete; those in other fields, two to six years.
Over fifty doctoral designations exist, many of them rare or no longer in use. As a title, the degree is commonly written in front of the name in abbreviated form, e.g., Dr. rer. nat. Max Mustermann or Dr. Max Mustermann, dropping the designation entirely. However, leaving out the designation is only allowed when the doctorate degree is not an honorary doctorate, which must be indicated by Dr. h.c. (from Latin honoris causa). Although the honorific does not become part of the name, holders can demand that the title appear in official documents. The title is not mandatory. The honorific is commonly used in formal letters. For holders of other titles, only the highest title is mentioned. In contrast to English, in which a person's name is preceded by at most one title (except in very ceremonious usage), the formal German mode of address permits several titles in addition to "Herr" or "Frau" (which, unlike "Mr" or "Ms", is not considered a title at all, but an Anrede or "address"), including repetitions in the case of multiple degrees, as in "Frau Prof. Dr. Dr. Schmidt", for a person who would be addressed as "Prof. Schmidt" in English.
In the German university system it is common to write two doctoral theses, the inaugural thesis (Inauguraldissertation), completing a course of study, and the habilitation thesis (Habilitationsschrift), which opens the road to a professorship. Upon completion of the habilitation thesis, a Habilitation is awarded, which is indicated by appending habil. (habilitata/habilitatus) to the doctorate, e.g., Dr. rer. nat. habil. Max Mustermann. It is considered as an additional academic qualification rather than an academic degree formally. It qualifies the owner to teach at German universities (facultas docendi). The holder of a Habilitation receives the authorization to teach a certain subject (venia legendi). This has been the traditional prerequisite for attaining Privatdozent (PD) and employment as a full university professor. With the introduction of Juniorprofessuren—around 2005—as an alternative track towards becoming a professor at universities (with tenure), Habilitation is no longer the only university career track.
=== India ===
In India, doctorates are offered by universities. Entry requirements include master's degree. Some universities consider undergraduate degrees in professional areas such as engineering, medicine or law as qualifications for pursuing doctorate level degrees. Entrance examinations are held for almost all programs. In most universities, coursework duration and thesis is 3–7 years. The most common doctoral degree is Ph.D.
=== Italy ===
Until the introduction of the dottorato di ricerca in the mid-1980s, the laurea generally constituted the highest academic degree obtainable in Italy. The first institution in Italy to create a doctoral program was Scuola Normale Superiore di Pisa in 1927 under the historic name "Diploma di Perfezionamento". Further, the dottorato di ricerca was introduced by law and presidential decree in 1980, in a reform of academic teaching, training and experimentation in organisation and teaching methods.
Italy uses a three-level degree system following the Bologna Process. The first-level degree, called a laurea (Bachelor's degree), requires three years and a short thesis. The second-level degree, called a laurea magistrale (Master's degree), is obtained after two additional years, specializing in a branch of the field. This degree requires more advanced thesis work, usually involving academic research or an internship. The final degree is called a dottorato di ricerca (Ph.D.) and is obtained after three years of academic research on the subject and a thesis.
Alternatively, after obtaining the laurea or the laurea magistrale, one can complete a "Master's" (first-level Master's after the laurea; second-level Master's after the laurea magistrale) of one or two years, usually including an internship. An Italian "Master's" is not the same as a master's degree; it is intended to be more focused on professional training and practical experience.
Regardless of the field of study, the title for Bachelors Graduate students is Dottore/Dottoressa (abbrev. Dott./Dott.ssa, or as Dr.), not to be confused with the title for the Ph.D., which is instead Dottore/Dottoressa di Ricerca. A laurea magistrale grants instead the title of Dottore/Dottoressa magistrale. Graduates in the fields of Education, Art and Music are also called Dr. Prof. (or simply Professore) or Maestro. Many professional titles, such as ingegnere (engineer) are awarded only upon passing a post-graduation examination (esame di stato), and registration in the relevant professional association.
The Superior Graduate Schools in Italy (Italian: Scuola Superiore Universitaria), also called Schools of Excellence (Italian: Scuole di Eccellenza) such as Scuola Normale Superiore di Pisa and Sant'Anna School of Advanced Studies keep their historical "Diploma di Perfezionamento" title by law and MIUR Decree.
=== Japan ===
==== Dissertation-only ====
Until the 1990s, most natural science and engineering doctorates in Japan were earned by industrial researchers in Japanese companies. These degrees were awarded by the employees' former university, usually after years of research in industrial laboratories. The only requirement is submission of a dissertation, along with articles published in well-known journals. This program is called ronbun hakase (論文博士). It produced the majority of engineering doctoral degrees from national universities. University-based doctoral programs called katei hakase (課程博士), are gradually replacing these degrees. By 1994, more doctoral engineering degrees were earned for research within university laboratories (53%) than industrial research laboratories (47%). Since 1978, Japan Society for the Promotion of Science (JSPS) has provided tutorial and financial support for promising researchers in Asia and Africa. The program is called JSPS RONPAKU.
==== Professional degree ====
The only professional doctorate in Japan is the Juris Doctor, known as Hōmu Hakushi (法務博士) The program generally lasts two or three years. This curriculum is professionally oriented, but unlike in the US the program does not provide education sufficient for a law license. All candidates for a bar license must pass the bar exam (Shihou shiken), attend the Legal Training and Research Institute and pass the practical exam (Nikai Shiken or Shihou Shushusei koushi).
=== Netherlands and Flanders ===
The traditional academic system of the Netherlands provided basic academic diploma: propaedeuse and three academic degrees: kandidaat (the lowest degree), depending on gender doctorandus or doctoranda (drs.) (with equivalent degrees in engineering – ir. and law – mr.) and doctor (dr.). After successful completion of the first year of university, the student was awarded the propaedeutic diploma (not a degree). In some fields, this diploma was abolished in the 1980s. In physics and mathematics, the student could directly obtain a kandidaats (candidate) diploma in two years. The candidate diploma was all but abolished by 1989. It used to be attained after completion of the majority of courses of the academic study (usually after completion of course requirements of the third year in the program), after which the student was allowed to begin work on their doctorandus thesis. The successful completion of this thesis conveyed the doctoranda/us title, implying that the student's initial studies were finished. In addition to these 'general' degrees, specific titles equivalent to the doctorandus degree were awarded for law: meester (master) (mr.), and for engineering: ingenieur (engineer)(ir.). Following the Bologna protocol the Dutch adopted the Anglo-Saxon system of academic degrees. The old candidate's degree was revived to become the bachelor's degree and the doctorandus' (mr and ir degree) were replaced by master's degrees.
Students can only enroll in a doctorate system after completing a research university level master's degree; although dispensation can be granted on a case-by-case basis after scrutiny of the individual's portfolio. The most common way to conduct doctoral studies is to work as promovendus/assistent in opleiding (aio)/onderzoeker in opleiding (oio) (research assistant with additional courses and supervision), perform extensive research and write a dissertation consisting of published articles (over a period of four or more years). Research can also be conducted without official research assistant status, for example through a business-sponsored research laboratory.
The doctor's title is the highest academic title in the Netherlands and Flanders. In research doctorates the degree is always Ph.D. or dr. with no distinction between disciplines, and can only be granted by research universities.
==== Netherlands ====
Every Ph.D. thesis has to be promoted by research university staff member holding ius promovendi (the right to promote). In the Netherlands all full professors have ius promovendi, as well as other academic staff granted this right on individual basis by the board of their university (almost always senior associate professors). The promotor has the role of principal advisor and determines whether the thesis quality suffices and can be submitted to the examining committee. The examining committee is appointed by the academic board of the university based on recommendation of the promotor and consists of experts in the field. The examining committee reviews the thesis manuscript and has to approve or fail the thesis. Failures at this stage are rare because promotors generally not submit work they deem inadequate to the examining committee, supervisors and promotor lose prestige among their colleagues should they allow a substandard thesis to be submitted.
After examining committee approval, the candidate publishes the thesis (generally more than 100 copies) and sends it to the examining committee, colleagues, friends and family with an invitation to the public defence. Additional copies are kept in the university library and the Royal Library of the Netherlands.
The degree is awarded in a formal, public, defence session, in which the thesis is defended against critical questions of the "opposition" (the examining committee). Specific formalities differ between universities, for example whether a public presentation is given, either before or during the session, specific phrasing in the procedure, and dress code. In most protocols, candidates can be supported by paranymphs, a largely ceremonial role, but they are formally allowed to take over the defence on behalf of the candidate. Doctoral candidates The actual defence lasts exactly the assigned time slot (45 minutes to 1 hour exactly depending on the university) after which the defence is suspended by the bedel who stops the examination, frequently mid sentence. Failure during this session is possible, but extremely rare. After formal approval of the thesis and the defence by the examining committee in a closed discussion, the session is resumed and the promotor grants the degree and hands over the diploma to the candidate, and usually congratulates the candidate and gives a personal speech praising the work of the young doctor (laudatio), before the session is formally closed.
Dutch doctors may use PhD behind their name instead of the uncapitalized dr. before their name. Those who obtained a degree in a foreign country can only use one of the Dutch title dr. if their grade is approved as equivalent by the Dienst Uitvoering Onderwijs though according to the opportunity principle, little effort is spent in identifying such fraud.
Those who have multiple doctor (dr.) titles may use the title dr.mult. Those who have received honoris causa doctorates may use dr.h.c. before their own name.
The Dutch universities of technology (Eindhoven University of Technology, Delft University of Technology, University of Twente, and Wageningen University) also award a 2-year (industry oriented) Professional Doctorate in Engineering (PDEng), renamed EngD from September 2022 onwards, which does not grant the right to use the dr. title abbreviation. In 2023, a pilot started at universities of applied sciences with a professional doctoral programme, in which the focus is on applying knowledge to improve or solve professional processes or products.
==== Flanders ====
In Belgium's Flemish Community the doctorandus title was only used by those who actually started their doctoral work. Doctorandus is still used as a synonym for a Ph.D. student. The licentiaat (licensee) title was in use for a regular graduate until the Bologna reform changed the licentiaat degree to the master's degree (the Bologna reform abolished the two-year kandidaat degree and introduced a three-year academic bachelor's degree instead).
=== Poland ===
In Poland, an academic degree of doktor 'doctor' is awarded in sciences and arts upon an examination and defence of a doctoral dissertation. As Poland is a signatory to the Bologna Process, doctoral studies are a third cycle of studies following the bachelor's (licencjat) and master's (magister) degrees or their equivalents. Doctoral student is known as doktorant (masculine form) or doktorantka (feminine form). Doctorate is awarded within specified brach and discipline of science or art by university or research institute accredited by the minister responsible for higher education. The title is abbreviated to dr in nominative case.
Doctors may further go a habilitation process.
=== Russia ===
Introduced in 1819 in the Russian Empire, the academic title Doctor of the Sciences (Russian: Доктор наук) marks the highest academic level achievable by a formal process.
The title was abolished with the end of the Empire in 1917 and revived by the USSR in 1934 along with a new (lower) complementary degree of a Candidate [Doctor] of the Sciences' (Russian: Кандидат наук). This system is used since with minor adjustments.
The Candidate of the Sciences title is usually seen as roughly equivalent to the research doctorates in Western countries while the Doctor of the Sciences title is relatively rare and retains its exclusivity. Most "Candidates" never reach the "Doctor of the Sciences" title.
Similar title systems were adopted by many of the Soviet bloc countries.
=== Spain ===
Doctoral degrees are regulated by Royal Decree (R.D. 778/1998), Real Decreto (in Spanish). They are granted by the university on behalf of the king. Its diploma has the force of a public document. The Ministry of Science keeps a national registry of theses called TESEO. According to the National Institute of Statistics (INE), fewer than 5% of M.Sc. degree holders are admitted to Ph.D. programmes.
All doctoral programs are research-oriented. A minimum of 4 years of study is required, divided into 2 stages:
A 2-year (or longer) period of studies concludes with a public dissertation presented to a panel of 3 Professors. Upon approval from the university, the candidate receives a Diploma de Estudios Avanzados (part qualified doctor, equivalent to M.Sc.). From 2008 it is possible to substitute the former diploma by a recognized master program.
A 2-year (or longer) research period includes extensions for up to 10 years. The student must present a thesis describing a discovery or original contribution. If approved by their thesis director, the study is presented to a panel of 5 distinguished scholars. Any Doctor attending the public defense is allowed to challenge the candidate with questions. If approved, the candidate receives the doctorate. Four marks used to be granted: Unsatisfactory (Suspenso), Pass (Aprobado), Remarkable (Notable), "Cum laude" (Sobresaliente), and "Summa cum laude" (Sobresaliente Cum Laude). Those Doctors granted their degree "Summa Cum Laude" were allowed to apply for an "Extraordinary Award".
Since September 2012 and regulated by Royal Decree (R.D. 99/2011) (in Spanish), three marks can be granted: Unsatisfactory (No apto), Pass (Apto) and "Cum laude" (Apto Cum Laude) as maximum mark. In the public defense the doctor is notified if the thesis has passed or not passed. The Apto Cum Laude mark is awarded after the public defense as the result of a private, anonymous vote. Votes are verified by the university. A unanimous vote of the reviewers nominates Doctors granted Apto Cum Laude for an "Extraordinary Award" (Premio Extraordinario de Doctorado).
In the same Royal Decree the initial 3-year study period was replaced by a Research master's degree (one or two years; Professional master's degrees do not grant direct access to Ph.D. Programs) that concludes with a public dissertation called Trabajo de Fin de Máster or Proyecto de Fin de Máster. An approved project earns a master's degree that grants access to a Ph.D. program and initiates the period of research.
A doctorate is required in order to teach at the university. Some universities offer an online Ph.D. model.
Only Ph.D. holders, Grandees and Dukes can sit and cover their heads in the presence of the King.
From 1857, Complutense University was the only one in Spain authorised to confer the doctorate. This law remained in effect until 1954, when the University of Salamanca joined in commemoration of its septcentenary. In 1970, the right was extended to all Spanish universities.
All doctorate holders are reciprocally recognised as equivalent in Germany and Spain (according to the "Bonn Agreement of November 14, 1994").
=== United Kingdom ===
==== History of the UK doctorate ====
The doctorate has long existed in the UK as, originally, the second degree in divinity, law, medicine and music. But it was not until the late 19th century that the research doctorate, now known as the higher doctorate, was introduced. The first higher doctorate was the Doctor of Science at Durham University, introduced in 1882. This was soon followed by other universities, including the University of Cambridge establishing its ScD in the same year, the University of London transforming its DSc from an advanced study course to a research degree in 1885, and the University of Oxford establishing its Doctor of Letters (DLitt) in 1900.
The PhD was adopted in the UK following a joint decision in 1917 by British universities, although it took much longer for it to become established. Oxford became the first university to institute the new degree, although naming it the DPhil. The PhD was often distinguished from the earlier higher doctorates by distinctive academic dress. At Cambridge, for example, PhDs wear a master's gown with scarlet facings rather than the full scarlet gown of the higher doctors, while the University of Wales gave PhDs crimson gowns rather than scarlet. Professional doctorates were introduced in Britain in the 1980s and 1990s. The earliest professional doctorates were in the social sciences, including the Doctor of Business Administration (DBA), Doctor of Education (EdD) and Doctor of Clinical Psychology (DClinPsy).
==== British doctorates today ====
Today, except for those awarded honoris causa (honorary degrees), all doctorates granted by British universities are research doctorates, in that their main (and in many cases only) component is the submission of an extensive and substantial thesis or portfolio of original research, examined by an expert panel appointed by the university. UK doctorates are categorised as:
Doctorates
Subject specialist research – normally PhD/DPhil; the most common form of doctorate
Integrated subject specialist doctorates – integrated PhDs including teaching at master's level
Doctorates by publication – PhD by Published Works; only awarded infrequently
Professional / practice-based / practitioner doctorates – e.g. EdD, ProfDoc/DProf, EngD, etc.; usually include taught elements and have an orientation that combines professional and academic aspects
Higher doctorates
e.g. DD, LLD, DSc, DLitt; higher level than doctorates, usually awarded either for a substantial body of work over an extended period or as honorary degrees.
The Quality Assurance Agency states in the Framework for Higher Education Qualifications of UK Degree-Awarding Bodies (which covers doctorates but not higher doctorates) that:
Doctoral degrees are awarded to students who have demonstrated:
the creation and interpretation of new knowledge, through original research or other advanced scholarship, of a quality to satisfy peer review, extend the forefront of the discipline, and merit publication
a systematic acquisition and understanding of a substantial body of knowledge which is at the forefront of an academic discipline or area of professional practice
the general ability to conceptualise, design and implement a project for the generation of new knowledge, applications or understanding at the forefront of the discipline, and to adjust the project design in the light of unforeseen problems
a detailed understanding of applicable techniques for research and advanced academic enquiry
In the UK, the doctorate is a qualification awarded at FHEQ level 8/level 12 of the FQHEIS on the national qualifications frameworks. The higher doctorates are stated to be "A higher level of award", which is not covered by the qualifications frameworks.
==== Subject specialist doctorates ====
These are the most common doctorates in the UK and are normally awarded as PhDs. While the master/apprentice model was traditionally used for British PhDs, since 2003 courses have become more structured, with students taking courses in research skills and receiving training for professional and personal development. However, the assessment of the PhD remains based on the production of a thesis or equivalent and its defence at a viva voce oral examination, normally held in front of at least two examiners, one internal and one external. Access to PhDs normally requires an upper second class or first class bachelor's degree, or a master's degree. Courses normally last three years, although it is common for students to be initially registered for MPhil degrees and then formally transferred onto the PhD after a year or two. Students who are not considered likely to complete a PhD may be offered the opportunity to complete an MPhil instead.
Integrated doctorates, originally known as 'New Route PhDs', were introduced from 2000 onwards. These integrate teaching at master's level during the first one or two years of the degree, either alongside research or as a preliminary to starting research. These courses usually offer a master's-level exit degree after the taught courses are completed. While passing the taught elements is often required, examination of the final doctorate is still by thesis (or equivalent) alone. The duration of integrated doctorates is a minimum of four years, with three years spent on the research component.
In 2013, Research Councils UK issued a 'Statement of Expectations for Postgraduate Training', which lays out the expectations for training in PhDs funded by the research councils. In the latest version (2016), issued together with Cancer Research UK, the Wellcome Trust and the British Heart Foundation, these include the provision of careers advice, in-depth advanced training in the subject area, provision of transferable skills, training in experimental design and statistics, training in good research conduct, and training for compliance with legal, ethical and professional frameworks. The statement also encourages peer-group development through cohort training and/or Graduate schools.
==== Higher doctorates ====
Higher doctorates are awarded in recognition of a substantial body of original research undertaken over the course of many years. Typically the candidate submits a collection of previously published, peer-refereed work, which is reviewed by a committee of internal and external academics who decide whether the candidate deserves the doctorate. The higher doctorate is similar in some respects to the habilitation in some European countries. However, the purpose of the award is significantly different. While the habilitation formally determines whether an academic is suitably qualified to be a university professor, the higher doctorate does not qualify the holder for a position but rather recognises their contribution to research.
Higher doctorates were defined by the UK Council for Graduate Education (UKCGE) in 2013 as:
an award that is at a level above the PhD (or equivalent professional doctorate in the discipline), and that is typically gained not through a defined programme of study but rather by submission of a substantial body of research-based work.
In terms of number of institutions offering the awards, the most common doctorates of this type in UKCGE surveys carried out in 2008 and 2013 were the Doctor of Science (DSc), Doctor of Letters (DLitt), Doctor of Law (LLD), Doctor of Music (DMus) and Doctor of Divinity (DD); in the 2008 survey the Doctor of Technology (DTech) tied with the DD. The DSc was offered by all 49 responding institutions in 2008 and 15 out of 16 in 2013 and the DLitt by only one less in each case, while the DD was offered in 10 responding institutions in 2008 and 3 in 2013. In terms of number of higher doctorates awarded (not including honorary doctorates) the DSc was most popular, but the number of awards was very low: the responding institutions had averaged an award of at most one earned higher doctorate per year over the period 2003–2013.
==== Honorary degrees ====
Most British universities award degrees honoris causa to recognise individuals who have made a substantial contribution to a particular field. Usually an appropriate higher doctorate is used in these circumstances, depending on the candidate's achievements. However, some universities differentiate between honorary and substantive doctorates, using the degree of Doctor of the University (D.Univ.) for these purposes, and reserve the higher doctorates for formal academic research.
=== United States ===
U.S. research doctorates are awarded for advanced study followed by successfully completing and defending independent research presented in the form of a dissertation. Professional degrees may use the term "doctor" in their titles, such as Juris Doctor and Doctor of Medicine, but these degrees rarely contain an independent research component and are not research doctorates. Law school graduates, although awarded the J.D. degree, are not normally addressed as "doctor". In legal studies, the Doctor of Juridical Science is considered the equivalent to a Ph.D.
Many American universities offer the PhD followed by a professional doctorate or joint PhD with a professional degree. Often, PhD work is sequential to the professional degree, e.g., PhD in law after a JD or equivalent in physical therapy after DPT, in pharmacy after Pharm.D. Such professional degrees are referred to as an entry-level doctorate program and Ph.D. as a post-professional doctorate.
==== Research degrees ====
The most common research doctorate in the United States is the Doctor of Philosophy (Ph.D.). This degree was first awarded in the U.S. at the 1861 Yale University commencement. The University of Pennsylvania followed in 1871, with Cornell University (1872), Harvard (1873), Michigan (1876) and Princeton (1879) following suit. Controversy and opposition followed the introduction of the Ph.D. into the U.S. educational system, lasting into the 1950s, as it was seen as an unnecessary artificial transplant from a foreign (Germany) educational system, which corrupted a system based on England's Oxbridge model.
Ph.D.s and other research doctorates in the U.S. typically entail successful completion of coursework, passing a comprehensive examination, and defending a dissertation.
The median number of years for completion of U.S. doctoral degrees is seven. Doctoral applicants were previously required to have a master's degree, but many programs accept students immediately following undergraduate studies. Many programs gauge the potential of applicants to their program and grant a master's degree upon completion of the necessary course work. When so admitted, the student is expected to have mastered the material covered in the master's degree despite not holding one, though this tradition is under heavy criticism. Successfully finishing Ph.D. qualifying exams confers Ph.D. candidate status, allowing dissertation work to begin.
The International Affairs Office of the U.S. Department of Education has listed 18 frequently awarded research doctorate titles identified by the National Science Foundation (NSF) as representing degrees equivalent in research content to the Ph.D.
==== Professional degrees ====
Many fields offer professional doctorates (or professional master's degrees) such as engineering, pharmacy, medicine, etc., that require such degrees for professional practice or licensure. Some of these degrees are also termed "first professional degrees", since they are the first field-specific master's or doctoral degrees.
A Doctor of Engineering (DEng) is a professional degree. In contrast to a PhD in Engineering where students usually conduct original theory-based research, DEng degrees are built around applied coursework and a practice-led project and thus designed for working engineers in the industry. DEng students defend their thesis at the end of their study before a thesis committee in order to be conferred a degree.
A Doctor of Pharmacy is awarded as the professional degree in pharmacy replacing a bachelor's degree. It is the only professional pharmacy degree awarded in the US. Pharmacy programs vary in length between four years for matriculants with a B.S./B.A. to six years for others.
In the twenty-first century professional doctorates appeared in other fields, such as the Doctor of Audiology in 2007. Advanced Practice Registered Nurses were expected to completely transition to the Doctor of Nursing Practice by 2015, and physical therapists to the Doctor of Physical Therapy by 2020. Professional associations play a central role in this transformation amid criticisms on the lack of proper criteria to assure appropriate rigor. In many cases master's-level programs were relabeled as doctoral programs.
== Revocation ==
A doctoral degree can be revoked or rescinded by the university that awarded it. Possible reasons include plagiarism, criminal or unethical activities of the holder, or malfunction or manipulation of academic evaluation processes.
== See also ==
Postdoctoral researcher
Compilation thesis
Habilitation thesis
Doctor (title)
Eurodoctorate
List of fields of doctoral studies
== Notes ==
== References == | Wikipedia/Higher_doctorate |
The Edmund A. Walsh School of Foreign Service (SFS) is the school of international relations at Georgetown University in Washington, D.C. It grants degrees at both undergraduate and graduate levels. Founded in 1919, SFS is the oldest continuously operating school for international affairs in the United States, predating the U.S. Foreign Service by six years.
SFS was established by Edmund A. Walsh with the goal of preparing Americans for various international professions in the wake of expanding U.S. involvement in world affairs after World War I. Today, the school hosts a student body of approximately 2,250 from over 100 nations each year. It offers an undergraduate program based in the liberal arts, which leads to the Bachelor of Science in Foreign Service (BSFS) degree, as well as eight interdisciplinary graduate programs.
Based in Washington, D.C., the school also maintains campuses in Doha, Qatar, and Jakarta, Indonesia. SFS is a founding member of the Association of Professional Schools of International Affairs (APSIA), a consortium of the world's leading public policy, public administration, and international affairs schools.
== History ==
=== 20th century ===
With the help of Georgetown University president Fr. John B. Creeden, S.J., Fr. Walsh spearheaded the founding of the School of Foreign Service and its establishment was announced on November 25, 1919. The school's use of the name “Foreign Service” preceded the formal establishment of the U.S. Foreign Service by six years. The school was envisioned by Fr. Walsh to prepare students for all major forms of foreign representation from commercial, financial, consular to diplomatic.
In 1921, it graduated its first class of Bachelor of Science in Foreign Service (BSFS) undergraduate students. The following year, the school began to offer the first international relations graduate program in the United States, the Master of Science in Foreign Service (MSFS).
In August 1932, the SFS was moved to the Healy Hall, a National Historic Landmark. In 1958, two years after the death of Fr. Walsh, the school was renamed after him and moved to the Walsh Building in a ceremony dedicated by President Eisenhower in honor of Fr. Walsh.
In 1936, the SFS Division of Business and Public Administration launched the Bachelor of Science in Business Administration (BSBA) degree. In 1957, under the leadership of Fr. Joseph Sebes, S.J, the division was spun off from the SFS, becoming the School of Business Administration — later renamed McDonough School of Business in honor of Robert Emmett McDonough (SFS'49).
In 1962, the Center for Strategic and International Studies (CSIS) was founded at Georgetown University as a think tank to conduct policy studies and strategic analyses of political, economic and security issues throughout the world. When Henry Kissinger retired from his position as U.S. Secretary of State in 1977, he declined offers of professorship from Harvard, Yale, Penn, Columbia, and Oxford, and decided to teach at Georgetown SFS instead, making CSIS the base for his Washington operations. In 1986, the university's board of directors voted to sever all ties with CSIS.
Since 1982, the school has been housed in the Edward B. Bunn, S.J. Intercultural Center (ICC) on Georgetown's main campus. In 1989, the Salaam Intercultural Resource Center, which is located on the top floor of the ICC, was opened in a ceremony presided by President Jimmy Carter. The center is a gift by Hany M. Sala'am and has housed the school's MSFS program since 1989.
In 1975, the Center for Contemporary Arab Studies (CCAS) was launched as the first academic institution in the United States to focusing exclusively on the Arab world. CCAS is a National Resource Center on the Middle East and North Africa (NRC-MENA) and funded by Title VI grants from the U.S. Department of Education, in addition to donation from Gulf Cooperation Council (GCC) governments. In 1999, King Abdullah II of Jordan (MSFS'87) dedicated a new facility for the center.
In 1978, the Institute for the Study of Diplomacy (ISD) was founded to bring together diplomats, practitioners and scholars to study diplomatic statecraft theory and practice. Past ISD fellows include Georgian deputy prime minister Giorgi Baramidze and Chinese foreign minister Wang Yi. From 1975 until 2016, the ISD also awarded the Edward Weintal Prize for Diplomatic Reporting to journalists in recognition of their distinguished reporting on foreign policy and diplomacy.
In 1992, following the collapse of the Soviet Union and the Eastern Bloc, the SFS launched the Pew Economic Freedom Fellows Program to train future leaders of transitional states from Eastern Europe and post-Soviet countries. Notable fellows include Latvian finance minister Uldis Osis, Kazhastan deputy prime minister Kairat Kelimbetov, and Lithuania president Dalia Grybauskaite, who was later awarded an honorary Doctor of Humane Letters degree by Georgetown University in 2013.
In 1995, the Security Studies Program (SSP), which was founded in 1977 as the National Security Studies Program (NSSP) and hosted at the U.S. Department of Defense headquarters in the Pentagon, was moved to Georgetown's main campus and incorporated into the SFS.
=== 21st century ===
In 2002, the school studied the feasibility of opening a campus in Qatar Foundation's Education City in Doha, Qatar. In 2005, the School of Foreign Service in Qatar (SFS-Q) was officially opened and welcomed its first class of undergraduate students. In 2015, the school was renamed to Georgetown University in Qatar (GU-Q) as it broadened its remit to include executive masters and professional programs.
In 2005, Saudi prince Al-Waleed bin Talal gave $20 million to the school's Center for Muslim-Christian Understanding to promote interfaith understanding and the study of the Muslim world. The gift was the second-largest ever given to Georgetown at that point, and the center was renamed in his honor.
In 2011, following the United Nations Security Council Resolution 1325, U.S. Secretary of State Hillary Clinton launched the Georgetown Institute for Women, Peace and Security (GIWPS) and served as its founding chair.
In June 2023, the administrators announced the plan to rename the school in honor of the late Madeleine Albright, who served as a professor at SFS both before and after her tenure as U.S. secretary of state. It attracted criticism due to Albright's controversial legacy and the lack of consultation with the school's community members. In October 2023, Georgetown announced that it was no longer considering renaming the school after Albright.
In November 2023, Indonesian president Joko Widodo announced Georgetown's partnership with the Indonesian government to open a satellite campus in the country. In January 2025, Georgetown SFS Asia-Pacific (GSAP) campus was launched in Jakarta, Indonesia, to offer graduate masters and visiting student programs.
== Academics ==
=== Undergraduate program ===
The Bachelor of Science in Foreign Service (BSFS) degree is offered by the School of Foreign Service. The degree is rooted in the liberal arts. Following completion of the core requirements, students declare one of the following interdisciplinary majors:
Culture and Politics (CULP)
Global Business (GBUS)
International Economics (IECO)
International History (IHIS)
International Political Economy (IPEC)
International Politics (IPOL)
Regional and Comparative Studies (RCST)
Science, Technology, & International Affairs (STIA)
There is also a joint degree — Bachelor of Science in Business and Global Affairs — offered in partnership with the McDonough School of Business (MSB).
=== Graduate program ===
Graduate students can pursue eight interdisciplinary graduate degrees in the school:
Master of Science in Foreign Service (MSFS) with concentrations in:
Global Business, Finance & Society (GBFS)
Global Politics & Security (GPS)
International Development (IDEV)
Science, Technology, and International Affairs (STIA)
Master of Arts in Security Studies (SSP)
Master of Global Human Development (GHD)
Master of Arts in Arab Studies (MAAS)
Master of Arts in Asian Studies (MASIA)
Master of Arts in German and European Studies (MAGES)
Master of Arts in Eurasian, Russian and East European Studies (MAERES)
Master of Arts in Latin American Studies (CLAS)
There are two joint executive degrees offered in partnership with Georgetown's McDonough School of Business: the Global Executive MBA offered in collaboration with the ESADE Business School in Spain and the INCAE Business School in Costa Rica, and the MA in International Business and Policy (MA-IBP). The school's Institute for the Study of Diplomacy also offers the Executive Master in Diplomacy and International Affairs (EMDIA) at the SFS campuses in Doha, Qatar, and Jakarta, Indonesia. SFS is a member of the Association of Professional Schools of International Affairs (APSIA), a global consortium of schools that trains leaders in international affairs.
Additionally, exceptional undergraduate SFS students can apply for the accelerated bachelor’s/master’s dual-degree program, which allows enrollment in one of the graduate programs (e.g. BSFS/MSFS, BSFS/MASIA, etc.) during the final undergraduate year and completion of both degrees in approximately five years.
=== Certificates ===
Georgetown offers a number of undergraduate and graduate certificate programs: African studies, Arab studies, Asian studies, Australian & New Zealand studies, German and European studies, international business diplomacy (honors program), international development, Muslim-Christian understanding, Jewish civilization, justice & peace studies, Latin American studies, medieval studies, Russian & East European studies, social & political thought, and women's and gender studies.
== Rankings ==
Georgetown's programs in international relations have consistently ranked among the best in the world in surveys of the field's academics that have been published biennially since 2005 by Foreign Policy. In 2014 and in 2018 Foreign Policy ranked Georgetown's master's programs first in the world and its bachelor's programs fourth. In 2024, Georgetown's master's programs were ranked first by all three groups of respondents: international relations faculty, policymakers, and think tank staffers. Its bachelor's programs were ranked first by policymakers and think tank staffers and third by international relations faculty.
In a Pipeline to the Beltway survey of makers of American foreign-policy from 2011, Georgetown ranked second overall in the quality of preparation for a career in the U.S. government, regardless of degree earned. In 2023, U.S. News & World Report ranked Georgetown fifth for graduate studies in global policy and administration. In 2024, Niche ranked Georgetown first in the United States for international relations.
== Student life ==
There are a vast array of clubs and student organizations at Georgetown that students from the SFS join. The elected representative organization of the SFS is the SFS Academic Council (SFSAC), which advocates for the SFS student body and works with the Dean's Office to address student concerns, spearhead new initiatives, and coordinate events. The School of Foreign Service also sponsors a flagship peer-reviewed academic publication, the Georgetown Journal of International Affairs (GJIA), which is published by Johns Hopkins University Press and run by undergraduate and graduate students.
== Campuses ==
The School of Foreign Service main campus, which is part of the main campus of Georgetown University, is located in the Georgetown neighborhood in Northwest Washington, D.C. In 2005, it opened another campus, the School of Foreign Service in Qatar (also known as SFS-Q or GU-Q), in Qatar Foundation's Education City in Doha, Qatar. In 2025, the school opened a facility in Jakarta, Indonesia, known as Georgetown SFS Asia-Pacific (GSAP), in partnership with the Indonesian government. Many SFS undergraduates spend a minimum of one semester or a summer abroad, choosing from direct matriculation programs around the globe as well as programs of other universities and those run by Georgetown, including SFS-Q, GSAP and Villa Le Balze.
== List of deans ==
== Notable people ==
=== Notable faculty ===
Jan Karski, Polish Catholic nobleman, diplomat and military officer
Henry Kissinger, Professor of Diplomacy, 1977
Madeleine Jana Korbel Albright, the Mortara Distinguished Professor of Diplomacy
George John Tenet, Distinguished Professor in the Practice of Diplomacy
Victor Cha, Distinguished University Professor, D.S. Song-KF Endowed Chair in Government and International Affairs
David M. Edelstein, Vice Provost for Education
Lev Dobriansky, Professor of Economics
Anwar Ibrahim, Distinguished Visiting Professor
=== Notable alumni ===
Abdullah II of Jordan (1987), King of Jordan
Sheikha Moza bint Nasser, mother of the Emir (King of Qatar), co-founder and chair of the Qatar Foundation
Adel al-Jubeir (1984) Minister of State for Foreign Affairs of Saudi Arabia
John R. Allen, former commander of International Coalition in Afghanistan, President of Brookings Institution
Steve Bannon (1983), White House chief strategist and Counselor to the President under President Trump
José Durão Barroso (1987), President of the European Commission and former prime minister of Portugal
Philip Bilden (1986), U.S. secretary of the Navy nominee in the first Trump administration
Jean-Charles Brisard (born 1968), French international consultant
Bill Bryant, Seattle port commissioner from 2008 to 2015
George Casey (1970), U.S. Army chief of staff
Laura Chinchilla Miranda (1959), 46th president of Costa Rica
Joseph Cirincione (1983), former president of the Ploughshares Fund
Paul Clement (1988), U.S. solicitor general and acting U.S. attorney general
Bill Clinton (1968), 42nd president of the United States
Anne Dias-Griffin (1993), hedge fund manager
Stéphane Dujarric (1988), Spokesman for UN Secretaries-General Kofi Annan, Ban Ki-moon and António Guterres
Richard Durbin (1966), U.S. senator from Illinois, Majority Whip of the United States Senate
Felipe VI (1991), King of Spain
Luis Fortuño (1982), Governor of Puerto Rico
Dexter Goei (1993), CEO of Altice
Christopher Grady, Vice Chairman of U.S. Joint Chiefs of Staff
Dalia Grybauskaitė, President of Lithuania
Alexander Haig (1961), U.S. secretary of state under Ronald Reagan, Supreme Allied Commander Europe of NATO (1974–79)
Daniel Henninger, columnist, Deputy Editorial Page Editor The Wall Street Journal
Mushahid Hussain, Opposition Leader in Pakistan, candidate for President of Pakistan in 2008
James Matthew Jones (1983), global health expert and philanthropist
James L. Jones (1966), U.S. national security advisor under President Obama
Eugen Jurzyca, Minister of Education of Slovakia
John F. Kelly (1984), Retired Marine general, the 5th U.S. secretary of homeland security and White House chief of staff in the first Trump Administration
Kathleen Kingsbury (2001) Opinion Editor, New York Times
Željko Komšić, President of Bosnia and Herzegovina from 2006 to 2014
Taro Kono (1986), Foreign Minister of Japan
Gloria Macapagal Arroyo (1968), president of the Philippines from 2001 to 2010
David Malpass (1982), President of the World Bank
Denis McDonough (1996), President Obama's chief of staff and former deputy national security advisor, Secretary of Veteran's Affairs in Biden administration
Kayleigh McEnany (2010), CNN Commentator; press secretary to President Trump
Maeve Kennedy McKean (2009), attorney and U.S. health official
Mick Mulvaney (1989), Director of U.S. Office of Management and Budget and White House Chief of Staff under President Trump
Kirstjen Nielsen (1994), U.S. secretary of homeland security under President Trump
Darcy Olsen, CEO of the Goldwater Institute
Jon Ossoff, (2009), U.S. senator from Georgia
Sandra Oudkirk, first female director of the American Institute in Taiwan (AIT)
Armand Peschard-Sverdrup, Mexican political scientist
Pat Quinn (1969), Governor of Illinois
Carl Reiner (1943), actor, film producer, film director, Emmy Award winner
Tony Ressler (1981), billionaire and owner of the Atlanta Hawks
Matthew A. Reynolds (1986), former assistant secretary of state for legislative affairs (2008–2009)
Chris Sacca (1997), Founder of Lowercase Capital
Therese Shaheen (1980), Chairman of the American Institute of Taiwan, 2002–2004; businesswoman
Arjun Singh Sethi (2003), civil rights writer and lawyer
Debora Spar (1984), Former president, Barnard College at Columbia University, member of the board of directors of Goldman Sachs, first female president of Lincoln Center
Courtney Stadd (1981), NASA chief of staff from 2001 to 2003
Daniel Sullivan (1993), U.S. senator from Alaska
George Tenet (1976), Director of the CIA from 1997 to 2004
Matthew VanDyke, freedom fighter and Prisoner of War (POW) in the 2011 Libyan Civil War
Marcus Wallenberg, a banker and industrialist
Margaret Weichert (1989), deputy director for management in the Office of Management and Budget, Director of the U.S. Office of Personnel Management
Nawaf Obaid (1996), political scientist and former Saudi foreign policy advisor
Igor Danchenko (2009), geopolitical analyst known for sourcing the Steele dossier
Anthony Clark Arend (1980), professor of government and foreign service at Georgetown University
== References ==
=== Citations ===
=== Sources ===
Curran, Robert Emmett (2010a). A History of Georgetown University: The Quest for Excellence, 1889–1964. Vol. 2. Washington, D.C.: Georgetown University Press. ISBN 978-1-58901-689-7.
Curran, Robert Emmett (2010b). A History of Georgetown University: The Rise to Prominence, 1964–1989. Vol. 3. Washington, D.C.: Georgetown University Press. ISBN 978-1-58901-690-3.
== External links ==
Official website | Wikipedia/Bachelor_of_Science_in_Foreign_Service |
A Candidate of Sciences is a PhD-equivalent academic research degree in all the post-Soviet countries with the exception of Ukraine, and until the 1990s it was also awarded in Central and Eastern European countries. It is officially classified by UNESCO as ISCED level 8, "doctoral or equivalent". In those countries conferring the Candidate of Sciences degrees, a more advanced degree, Doctor of Sciences, is usually conferred as a higher doctorate.
The Candidate of Sciences degree may be recognized as a Doctor of Philosophy, usually in natural sciences, by scientific institutions in other countries.
== Overview ==
The degree was introduced in the USSR on 13 January 1934 by a decision of the Council of People's Commissars of the USSR, all previous degrees, ranks and titles having been abolished immediately after the October Revolution in 1917. Academic distinctions and ranks were viewed as survivals of capitalist inequality and hence were to be permanently eliminated. The original decree also recognized some degrees earned prior to 1917 in Tsarist Russia and elsewhere.
To attain the Candidate of Sciences degree, an individual must hold a Master's (Magistr) or a Specialist diploma, both one or (more typically) two year degrees in this system. Both of these prerequisites are post-bachelors (Bakalavr) degrees, bachelor's being four years of full-time study. The Candidate of Sciences degree requires a minimum of three years of full-time study during which the individual must conduct and publish advanced original research into a topic that is deemed significant or has practical economic or military potential.
In order to attain the rank of full Professor in these countries, a Doctor of Sciences degree is required in the same way that habilitation is required in Germany. This is also sometimes the case in the United States and the United Kingdom, where in addition to the possession of a doctoral (Ph.D.) degree, some volume of further research must be demonstrated.
== Procedure for attaining the degree ==
The work on a dissertation is commonly carried out during a postgraduate study period called aspirantura. Not all those who accomplish aspirantura will be invited to write a dissertation. An analogous situation may be found in American institutions where, after comprehensive examinations, a faculty may decide to award another Masters degree instead of continuing with the dissertation. It is performed either within an educational institution (such as a university) or a scientific research institution (such as an institute of the Russian Academy of Sciences network). It can also be carried out without a direct connection to the academy. In exceptional cases, the Candidate of Sciences degree may be awarded on the basis of published scholarly works without writing a thesis. In experimental sciences the dissertation is based on an independent research project conducted under the supervision of a professor, the results of which must be published in at least three papers in peer-review scientific journals.
A necessary prerequisite is taking courses in philosophy and foreign language, and passing a qualifying examination called "candidate minimum". In the Soviet Union, the candidate minimum included exams in the specialty field of the "dissertant", in a foreign language of his/her choice and in scientific communism. In post-Soviet Russia and other post-Soviet states, the latter examination was replaced by the one in philosophy, and in Russia recently in the history and philosophy of science; in Ukraine it was philosophy.
The dissertation is presented ("defended") before a committee called the Dissertation Council which is accredited at the educational or scientific institution. The Council consists of about 20 members, who are the leading specialists (including the academicians) in the field of the dissertation and who have been selected and empowered to serve for the council. The summary of the dissertation must be published before public defense in the form of "autoreferat" in about 150–200 copies, and distributed to major research organizations and libraries. The seeker of the degree must have an official "research supervisor". The dissertation must be delivered together with official references of several reviewers, called "opponents". In a procedure called the "defense of the dissertation" the dissertation is summarized before the commission, followed by speeches by the opponents or the reading of their references, and replies to the comments of the opponents and question of the Commission members by the aspirant.
If the defense is successful (66.6% majority of votes by the secret ballot voting by the members of the council), it is recommended and later must be approved by the central statewide board called Higher Attestation Commission or "Vysshaya attestacionnaya komissiya" or VAK (or by similar authority in other applicable countries). However, since end-2010s the dissertation councils accredited at some world-known educational units like Moscow and St. Petersburg State universities or top-level research centers are exempt from requirement to send the defended dissertations to the VAK for control. As of 2021 there were 29 such organizations (s. full list).
== Local characteristics ==
=== Former Czechoslovakia ===
In Czechoslovakia, the Candidate and Doctor of Sciences (Czech: Kandidát věd, Slovak: Kandidát vied) degrees were modeled precisely after the Soviet one by Law 60/1953 in 1953. Requirements to attain the degree were thus literally the same as in the USSR. Since all Czechoslovak top academic research institutions were dissolved after the Communist Putsch in 1948, the supreme academic authority was represented by the Czechoslovak Academy of Sciences, newly established in 1953. The degree could also be awarded by the Slovak Academy of Sciences and universities.
The abbreviation of the degree is CSc. (Latin: candidatus scientiarum), added behind the bearer's name and a comma.
There also have been other academic degrees in Czechoslovakia and its successional states, that incorporate the "Dr." abbreviation, e.g.
JUDr. (Latin: juris utriusque doctor, English: Doctor of Law, Czech: doktor práv, Slovak: doktor práv)
PhDr. (Latin: philosophiae doctor, English: Doctor of Philosophy, Czech: doktor filosofie, Slovak: doktor filozofie)
RNDr. (Latin: rerum naturalium doctor, English: Doctor of Natural Sciences, Czech: doktor přírodních věd, Slovak: doktor prírodných vied)
and others. These doctor degrees are not to be confused with a Ph.D., although its holders are addressed "doctor". Applicants need a master's degree (5 years +) or a comparable degree with excellent grades. This degree is stated before names and awarded after writing a rigorous thesis of 50.000 to 80.000 words and defending it at a viva voce and (rigorous) exam in at least 2-3 related fields of doctoral studies.
MUDr. (Latin: medicinae universae doctor) is a "Doctor of Medicine" degree equivalent to the North-American MD, attained after 6-year university studies.
MVDr. (Latin: medicinae veterinariae doctor) is a "Doctor of Veterinary" akin to DVM.
RSDr. (Latin: rerum socialium doctor) was a quasi-degree, awarded exclusively to functionaries of the Communist Party of Czechoslovakia (KSČ) during the Communist era, who either or not "graduated" from the Political College of the Central Committee of the Communist Party of Czechoslovakia. The leading subject taught was Marxism-Leninism and there was no need to have completed even a secondary school to attain the degree. RSDr. was also possible to attain at some military universities, however, contrary to the previous case, the applicant had to pass further exams.
=== Czech Republic ===
Granting CSc. was abolished in 1998 and replaced with Ph.D. or Th.D. (Czech: doktor) An applicant is required to have master's degree (or its equivalent, e.g. Engineer (Ing.) in technical and economic university programs or Doctor of Medicine (MUDr.), Doctor of Veterinary Medicine (MVDr.) in medical university programs), enroll in an approximately three-year post-graduate program and defend their dissertation before a panel of expert examiners appointed by the university.
=== Slovakia ===
Candidate was abolished in 1996 and replaced with PhD. (Slovak: doktor, in 1996-2002 officially in Latin: philosophiae doctor). Requirements are similar to the Czech system.
=== Poland ===
Since the medieval period, Polish tradition was to call Ph.D. equivalent as "doktor". Only for a short period of time between 1951 and 1958 the communist government tried to replace the title of "doktor" with "kandydat nauk" to follow the Soviet model.
=== Former Soviet Union, Russia, Belarus ===
In the USSR, there were at least three original scientific papers published and/or submitted required. At least one paper should be in one of the journals listed by the Higher Assessment Commission (VAK) of the Russian Ministry of Science. In Belarus, all the three publications have to be published in the journals listed by the VAK.
In 1971, there were 249,200 scientists holding the Candidate degree.
According to "Guidelines for the recognition of Russian qualifications in the other countries" Archived 2019-12-20 at the Wayback Machine, in countries with a two-tier system of doctoral degrees, the degree of Candidate of Sciences should be considered for recognition at the level of the first doctoral degree. In countries with only one doctoral degree, the degree of Candidate of Sciences should be considered for recognition as equivalent to this degree.
=== Kazakhstan ===
Kazakhstan previously followed the Soviet two-tier academic degree system, which included the Candidate of Sciences (Kazakh: ғылым кандидаты) and Doctor of Sciences (Kazakh: ғылым докторы), awarded and recognized by the Higher Attestation Commission under the Ministry of Education and Science of Kazakhstan (VAK RK). Following the country's accession to the Bologna Process in 2010, Kazakhstan transitioned to the terminal degree system, formally abolishing the Candidate of Sciences degree in 2011 through Order No. 127 by the Minister of Education and Science "On Approval of the Rules for Awarding Degrees". The new system now recognizes Doctor of Philosophy (Kazakh: доктор) and Doctor of Profile degrees, aligning with international standards.
Although the Candidate of Sciences degree is no longer awarded, individuals who hold this qualification may still receive recognition for their academic accomplishments in Kazakhstan, depending on the field and institution.
=== Ukraine ===
In 2014, with the adoption of the new Law of Ukraine "On Higher Education", the degree of Candidate of Sciences was replaced with the degree of Doctor of Philosophy (PhD). According to the new law, the degree of Candidate of Sciences is equated to the PhD degree (it is mentioned in the Candidate of Sciences diplomas issued since 2014).
In 2015, graduate students were enrolled in the Candidate of Sciences programs for the last time. The form "Candidate of Science" (singular) is used on the English-language page of bilingual diplomas of Candidate of Sciences issued since 2014 (until 2014, the Candidate of Sciences diplomas in Ukraine contained the Ukrainian text only).
As of 2024, those who were enrolled in the Candidate of Sciences programs until 2015 still may defend their theses and obtain the Candidate of Sciences degree.
== Branches of science ==
Depending on the specialty of research in the dissertation, a candidate degree in Russia is awarded one of the following degrees:
agricultural sciences (abbr.: к. с.-х. н.);
architecture (abbr.: к. арх.);
art criticism (abbr.: к. иск.);
biological sciences (abbr.: к. б. н.);
chemical sciences (abbr.: к. х. н.);
culturology (abbr.: к. культ.);
economic sciences (abbr.: к. э. н.);
engineering sciences (abbr.: к. т. н.);
geographic sciences (abbr.: к. геогр. н.);
geologo-mineralogical sciences (abbr.: к. г.-м. н.) [in the USSR, Russia, and Belarus] or geological sciences (abbr.: к. геол. н.) [in Ukraine];
historical sciences (abbr.: к. ист. н.);
juridical sciences (abbr.: к. ю. н.);
medical sciences (abbr.: к. м. н.);
military sciences (abbr.: к. воен. н.);
pedagogic sciences (abbr.: к. пед. н.);
pharmaceutical sciences (abbr.: к. фарм. н.);
philological sciences (abbr.: к. филол. н.);
philosophical sciences (abbr.: к. филос. н.);
physico-mathematical sciences (abbr.: к. ф.-м. н.);
political sciences (abbr.: к. полит. н.);
psychological sciences (abbr.: к. пс. н.);
sociological sciences (abbr.: к. соц. н.);
state administration (abbr.: к. н. держ. упр.) [only in Ukraine];
theology (abbr.: к. богосл.) [only in Russia];
veterinary sciences (abbr.: к. ветеринар. н.).
Previously, there was also the degree of "naval sciences" (abbr.: к. воен.-мор. н.). For some time (in the 1940s) there was also the degree of "candidate of art criticism sciences" (abbr.: к. иск. н.).
Some specialties permit the award of the candidate degree for several variants of branches of science, depending on the dominant subject area of the dissertation; e. g., specialty 02.00.04 (physical chemistry) can be awarded the degree of candidate of physico-mathematical, technical, or chemical sciences. However, for each dissertation only one branch of science can be chosen.
== Notes ==
== See also ==
Doctor of Philosophy
Doktor nauk
Education in Belarus
Education in Russia
Education in Ukraine
== References == | Wikipedia/Candidate_of_Sciences |
The Cornell University College of Arts and Sciences (CAS or A&S) is an academic college at Cornell University. It has been part of the university since its founding in 1865, although its name has changed over time. It is the largest of Cornell University's colleges and schools with 4,251 undergraduate and 1,301 students and 526 faculty.
The college grants bachelor's degrees, and masters and doctorates through affiliation with the Cornell University Graduate School. Its major academic buildings are located on the Arts Quad of Cornell University's main campus in Ithaca, New York, which includes some of the university's oldest and most historic buildings.
== History ==
=== 19th century ===
When it was founded in 1865, Cornell University's faculty was initially undifferentiated. With the founding of the Cornell Law School in 1886 and the concomitant self-segregation of the school's lawyers, however, departments and colleges began to be formed at the university.
=== 20th century ===
In 1903, the academic division that ultimately became the College of Arts and Sciences was renamed as the Academic Department. The College endowed the first professorships in American history, musicology, and American literature.
From 1923 to 1945, Cornell professor Robert Morris Ogden, a professor of psychology and expert on Gestalt psychology, served as the dean of the College of Arts and Sciences.
=== 21st century ===
As of 2009, the College of Arts and Sciences teaches 4,100 undergraduates, with 600 full-time faculty members plus a number of lecturers, who teach 2,200 courses.
In June 2018, Ray Jayawardhana was named the 22nd dean. On July 13, 2023, Rachel Bean succeeded Jayawardhana as interim dean.
== Arts Quadrangle ==
The Arts Quad on the campus of Cornell University is the site of the university's original academic buildings, which are associated with most of the College of Arts and Sciences' classes and programs. On the western side of the quad, at the top of Libe Slope, are Morrill Hall (completed in 1866), McGraw Hall (1872) and White Hall (1868). All of these buildings are built with native Cayuga bluestone to reflect Ezra Cornell's utilitarianism and are known as Stone Row. The statue of Ezra Cornell, dating back to 1919, stands between Morrill and McGraw Halls. Across from this statue, in front of Goldwin Smith Hall, sits the statue of Andrew Dickson White, Cornell's other co-founder and its first president.
Lincoln Hall (1888) also stands on the eastern face of the quad next to Goldwin Smith Hall. On the northern face are the domed Sibley Hall and Tjaden Hall (1883). Just off of the quad on the Slope, next to Tjaden, stands the Herbert F. Johnson Museum of Art, designed by I. M. Pei (1973). Stimson Hall (1902), Olin Library (1959) and Uris Library (1892), with Cornell's landmark clocktower, McGraw Tower, stand on the southern end of the quad.
Olin Library replaced Boardman Hall (1892), the original location of the Cornell Law School. In 1992, an underground addition was made to the quad with Kroch Library, an extension of Olin Library that houses several special collections of the Cornell University Library, including the Division of Rare and Manuscript Collections.
Klarman Hall, the first new humanities building at Cornell in over 100 years, opened in 2016. Klarman houses the offices of Comparative Literature and Romance Studies. The building is connected to, and surrounded on three sides by, Goldwin Smith Hall and fronts East Avenue.
Legends and lore about the Arts Quad and its statues can be found at Cornelliana.
== Academics ==
=== Majors ===
The College of Arts and Sciences offers both undergraduate and graduate (through the Graduate School) degrees. The only undergraduate degree is the Bachelor of Arts.
The faculties within the college are:
*Africana Studies was an independent center reporting directly to the Provost until July 1, 2011.
*The English department was renamed the Department of Literatures in English in October 2020 in response to national anti-racism movements.
== Admissions ==
Admission into the college is extremely competitive. The undergraduate program's 7.3% acceptance rate is below Cornell's 8.4% overall undergraduate acceptance rate. Furthermore, Arts and Sciences has the second lowest acceptance rate of any Cornell college, behind the Dyson School (2.9%).
== References ==
== External links ==
Official website | Wikipedia/Cornell_University_College_of_Arts_and_Sciences |
A Doctor of Sciences is a higher doctoral degree in the Russian Empire, Soviet Union and many Commonwealth of Independent States countries. One of the prerequisites of receiving a Doctor of Sciences degree is having a PhD-equivalent Candidate of Sciences degree beforehand. In addition, the Doctor of Sciences conferral also requires applicants to demonstrate significant and outstanding contributions to their research field. This degree is generally regarded as an honor and recognition for lifetime academic achievements rather than an ordinary academic degree by courses and theses.
== History ==
The "Doctor of Sciences" degree was introduced in the Russian Empire in 1819 and abolished in 1917. Later it was revived in the USSR on January 13, 1934, by a decision of the Council of People's Commissars of the USSR. By the same decision, a lower degree, "Candidate of Sciences" (kandidat nauk), roughly the Russian equivalent to the research doctorate in other countries, was first introduced. This system was generally adopted by the USSR/Russia and many post-Soviet/Eastern bloc states, including Bulgaria, Belarus, former Czechoslovakia, Kazakhstan, Poland (since abolished), and Ukraine.
But the former Yugoslav degree "Doktor nauka" / "Доктор наука" / "Doktor znanosti", still awarded by Bosnia Herzegovina, Croatia, Montenegro, North Macedonia, Serbia, and Slovenia follows the Bologna Process and is therefore equivalent to either a PhD, or to a higher doctorate, depending on the institution awarding the degree.
== Admission ==
Doctor of Sciences degrees are conferred by a national government agency called the Higher Attestation Commission (Vysshaya attestatsionnaya komissiya, VAK) on the solicitation by the specialized dissertation committee before which the candidate has defended her or his dissertation. Such committees are created in academic institutions with established research record and are accredited by VAK. The total number of committee members is typically about 20, all holding the Doctor of Sciences degree. The area of research specialization of at least five committee members must match the profile of the materials submitted by the doctoral candidate for the consideration. The candidate must conduct independent research. Therefore, no academic supervisor is required; moreover, typically the candidate is an established scholar him/herself, supervising a few Ph.D. students while working towards his or her Doctor of Sciences dissertation. However, it is normal practice when an experienced consultant is appointed to help the scholar with identifying the research problem and finding the approach to solving it; yet this is not technically regarded a supervision.
The procedures of conferring of both Kandidat and Doktor academic degrees are more formal and different from conferring a Ph.D. degree in Western universities. In particular, for the Doktor, the academic institution, where the scholar is affiliated as a doctoral candidate, must conduct a preliminary review of the research results and personal contribution made by the candidate and, depending on findings, elect whether to render formal support or not. By definition, this highly prestigious degree can be conferred only for a significant contribution to science and/or technology based on a public defense of a thesis, monograph, or (in rare cases) of a set of outstanding publications in peer-reviewed journals. The defense must be held at the session of a Specialized Dissertation Committee accredited by VAK. Prior to the defense, three referees holding Doctor of Sciences degrees themselves (the so-called "official opponents") must submit their written motivated assessments of the thesis. One more similar assessment is to be provided by some university or academic institution, working in the same field of science or technology, and in addition several other reviewers must mail their conclusions made based on a thesis summary (usually a 32-page brochure in natural sciences and 48 pages in social sciences).
In the former USSR, this degree is considered a sufficient credential for tenured full professorship at any institution of higher education. Unless an academic holds a Doctor of Sciences, she or he can make it to a full professor only through 15 years or more of outstanding teaching service on the university level. At least one published and widely accepted textbook and the degree of Kandidat Nauk are required in the latter case, anyway. A Doctor of Sciences degree holder can become a tenured full professor after just one year of teaching experience in a non-tenured faculty position. A degree of Doctor of Sciences also enables its holders to claim an academic rank of a professor awarded by VAK or a new rank of a "Professor of the Russian Academy of Sciences" established in 2015.
The Doctor of Sciences thus has no academic equivalent in North America, as it is a post-doctoral degree.
The German Habilitation and, to some extent, the French habilitation à diriger des recherches (HDR) are comparable to it, as are the British higher doctorates (e.g. Doctor of Science), although the last-mentioned are not required for career advancement. On the average, only 10 per cent of Kandidats eventually earn a Doktor degree. Although some exceptionally talented researchers in mathematics do earn Doctor of Sciences in their late 20s, the average age of the scholars reaching Doktor in most disciplines is about 50; this implicitly indicates the amount of contribution that must be made.
According to the Ministry of Education and Science of the Russian Federation, "In countries with a two-tier system of doctoral degrees, the degree of Doctor Nauk should be considered for recognition at the level of the second doctoral degree. In countries with only one doctoral degree, the degree of Doctor Nauk should be considered for recognition as equivalent to this degree."
According to guidelines published by the Russian Academy of Sciences:
д. арх. (Russian: доктор архитектуры) – Doctor of Sciences in Architecture
д. б. н. (Russian: доктор биологических наук) – Doctor of Sciences in Biological Sciences
д. вет. н. (Russian: доктор ветеринарных наук) – Doctor of Sciences in Veterinary Sciences
д. воен. н. (Russian: доктор военных наук) – Doctor of Sciences in Military Sciences
д. г. н. (Russian: доктор географических наук) – Doctor of Sciences in Geographical Sciences
д. г.-м. н. (Russian: доктор геолого-минералогических наук) – Doctor of Sciences in Geological and Mineralogical Sciences
д. и. н. (Russian: доктор исторических наук) – Doctor of Sciences in Historical Sciences
д. иск. (Russian: доктор искусствоведения) – Doctor of Sciences in Study of Art
д. м. н. (Russian: доктор медицинских наук) – Doctor of Sciences in Medical Sciences
д. п. н. (Russian: доктор психологических наук) – Doctor of Sciences in Psychological Sciences
д. пед. н. (Russian: доктор педагогических наук) – Doctor of Sciences in Pedagogical Sciences
д. полит. н. (Russian: доктор политических наук) – Doctor of Sciences in Political Sciences
д. с.-х. н. (Russian: доктор сельскохозяйственных наук) – Doctor of Sciences in Agricultural Sciences
д. социол. н. (Russian: доктор социологических наук) – Doctor of Sciences in Sociological Sciences
д. т. н. (Russian: доктор технических наук) – Doctor of Sciences in Technical Sciences
д. теол. н. (Russian: доктор теологических наук) – Doctor of Sciences in Religious Sciences
д. ф. н. (Russian: доктор филологических наук) – Doctor of Sciences in Philological Sciences
д. фарм. н. (Russian: доктор фармацевтических наук) – Doctor of Sciences in Pharmaceutics
д. ф.-м. н. (Russian: доктор физико-математических наук) – Doctor of Sciences in Physical and Mathematical Sciences
д. филос. н. (Russian: доктор философских наук) – Doctor of Sciences in Philosophical Sciences
д. х. н. (Russian: доктор химических наук) – Doctor of Sciences in Chemical Sciences
д. э. н. (Russian: доктор экономических наук) – Doctor of Sciences in Economics
д. ю. н. (Russian: доктор юридических наук) – Doctor of Sciences in Jurisprudence
According to the International Standard Classification of Education, for purposes of international educational statistics:
D.Sc.; D.Phil. to Doctor of Sciences in Philosophy,
D.Lit.; Dr.Litt. to Doctor of Sciences in Literature,
D.Sc.; Dr.Nat.Sci. to Doctor of Sciences of Natural Science,
LL.D.; D.Sci.Jus. to Doctor of Sciences of Legal Science.
== Notes ==
== See also ==
Academic degree
Candidate of Sciences
Doctor of Medicine
Education in Russia
Habilitation
== References == | Wikipedia/Doctor_of_Sciences |
In thermodynamics, an irreversible process is a process that cannot be undone. All complex natural processes are irreversible, although a phase transition at the coexistence temperature (e.g. melting of ice cubes in water) is well approximated as reversible.
A change in the thermodynamic state of a system and all of its surroundings cannot be precisely restored to its initial state by infinitesimal changes in some property of the system without expenditure of energy. A system that undergoes an irreversible process may still be capable of returning to its initial state. Because entropy is a state function, the change in entropy of the system is the same whether the process is reversible or irreversible. However, the impossibility occurs in restoring the environment to its own initial conditions. An irreversible process increases the total entropy of the system and its surroundings. The second law of thermodynamics can be used to determine whether a hypothetical process is reversible or not.
Intuitively, a process is reversible if there is no dissipation. For example, Joule expansion is irreversible because initially the system is not uniform. Initially, there is part of the system with gas in it, and part of the system with no gas. For dissipation to occur, there needs to be such a non uniformity. This is just the same as if in a system one section of the gas was hot, and the other cold. Then dissipation would occur; the temperature distribution would become uniform with no work being done, and this would be irreversible because you couldn't add or remove heat or change the volume to return the system to its initial state. Thus, if the system is always uniform, then the process is reversible, meaning that you can return the system to its original state by either adding or removing heat, doing work on the system, or letting the system do work. As another example, to approximate the expansion in an internal combustion engine as reversible, we would be assuming that the temperature and pressure uniformly change throughout the volume after the spark. Obviously, this is not true and there is a flame front and sometimes even engine knocking. One of the reasons that Diesel engines are able to attain higher efficiency is that the combustion is much more uniform, so less energy is lost to dissipation and the process is closer to reversible.
The phenomenon of irreversibility results from the fact that if a thermodynamic system, which is any system of sufficient complexity, of interacting molecules is brought from one thermodynamic state to another, the configuration or arrangement of the atoms and molecules in the system will change in a way that is not easily predictable. Some "transformation energy" will be used as the molecules of the "working body" do work on each other when they change from one state to another. During this transformation, there will be some heat energy loss or dissipation due to intermolecular friction and collisions. This energy will not be recoverable if the process is reversed.
Many biological processes that were once thought to be reversible have been found to actually be a pairing of two irreversible processes. Whereas a single enzyme was once believed to catalyze both the forward and reverse chemical changes, research has found that two separate enzymes of similar structure are typically needed to perform what results in a pair of thermodynamically irreversible processes.
== Absolute versus statistical reversibility ==
Thermodynamics defines the statistical behaviour of large numbers of entities, whose exact behavior is given by more specific laws. While the fundamental theoretical laws of physics are all time-reversible, experimentally the probability of real reversibility is low and the former state of system and surroundings is recovered only to certain extent (see: uncertainty principle). The reversibility of thermodynamics must be statistical in nature; that is, it must be merely highly unlikely, but not impossible, that a system will lower in entropy. In other words, time reversibility is fulfilled if the process happens the same way if time were to flow in reverse or the order of states in the process is reversed (the last state becomes the first and vice versa).
== History ==
The German physicist Rudolf Clausius, in the 1850s, was the first to mathematically quantify the discovery of irreversibility in nature through his introduction of the concept of entropy. In his 1854 memoir "On a Modified Form of the Second Fundamental Theorem in the Mechanical Theory of Heat," Clausius states:
It may, moreover, happen that instead of a descending transmission of heat accompanying, in the one and the same process, the ascending transmission, another permanent change may occur which has the peculiarity of not being reversible without either becoming replaced by a new permanent change of a similar kind, or producing a descending transmission of heat.
Simply, Clausius states that it is impossible for a system to transfer heat from a cooler body to a hotter body. For example, a cup of hot coffee placed in an area of room temperature (~72 °F) will transfer heat to its surroundings and thereby cool down with the temperature of the room slightly increasing (to ~72.3 °F). However, that same initial cup of coffee will never absorb heat from its surroundings, causing it to grow even hotter, with the temperature of the room decreasing (to ~71.7 °F). Therefore, the process of the coffee cooling down is irreversible unless extra energy is added to the system.
However, a paradox arose when attempting to reconcile microanalysis of a system with observations of its macrostate. Many processes are mathematically reversible in their microstate when analyzed using classical Newtonian mechanics. This paradox clearly taints microscopic explanations of macroscopic tendency towards equilibrium, such as James Clerk Maxwell's 1860 argument that molecular collisions entail an equalization of temperatures of mixed gases. From 1872 to 1875, Ludwig Boltzmann reinforced the statistical explanation of this paradox in the form of Boltzmann's entropy formula, stating that an increase of the number of possible microstates a system might be in, will increase the entropy of the system, making it less likely that the system will return to an earlier state. His formulas quantified the analysis done by William Thomson, 1st Baron Kelvin, who had argued that:
The equations of motion in abstract dynamics are perfectly reversible; any solution of these equations remains valid when the time variable t is replaced by –t. On the other hand, physical processes are irreversible: for example, the friction of solids, conduction of heat, and diffusion. Nevertheless, the principle of dissipation of energy is compatible with a molecular theory in which each particle is subject to the laws of abstract dynamics.
Another explanation of irreversible systems was presented by French mathematician Henri Poincaré. In 1890, he published his first explanation of nonlinear dynamics, also called chaos theory. Applying chaos theory to the second law of thermodynamics, the paradox of irreversibility can be explained in the errors associated with scaling from microstates to macrostates and the degrees of freedom used when making experimental observations. Sensitivity to initial conditions relating to the system and its environment at the microstate compounds into an exhibition of irreversible characteristics within the observable, physical realm.
== Examples of irreversible processes ==
In the physical realm, many irreversible processes are present to which the inability to achieve 100% efficiency in energy transfer can be attributed. The following is a list of spontaneous events which contribute to the irreversibility of processes.
Ageing (this claim is disputed, as aging has been demonstrated to be reversed in mice. NAD+ and telomerase have also been demonstrated to reverse ageing.)
Death
Time
Heat transfer through a finite temperature difference
Friction
Plastic deformation
Flow of electric current through a resistance
Magnetization or polarization with a hysteresis
Unrestrained expansion of fluids
Spontaneous chemical reactions
Spontaneous mixing of matter of varying composition/states
A Joule expansion is an example of classical thermodynamics, as it is easy to work out the resulting increase in entropy. It occurs where a volume of gas is kept in one side of a thermally isolated container (via a small partition), with the other side of the container being evacuated; the partition between the two parts of the container is then opened, and the gas fills the whole container. The internal energy of the gas remains the same, while the volume increases. The original state cannot be recovered by simply compressing the gas to its original volume, since the internal energy will be increased by this compression. The original state can only be recovered by then cooling the re-compressed system, and thereby irreversibly heating the environment. The diagram to the right applies only if the first expansion is "free" (Joule expansion), i.e. there can be no atmospheric pressure outside the cylinder and no weight lifted.
== Complex systems ==
The difference between reversible and irreversible events has particular explanatory value in complex systems (such as living organisms, or ecosystems). According to the biologists Humberto Maturana and Francisco Varela, living organisms are characterized by autopoiesis, which enables their continued existence. More primitive forms of self-organizing systems have been described by the physicist and chemist Ilya Prigogine. In the context of complex systems, events which lead to the end of certain self-organising processes, like death, extinction of a species or the collapse of a meteorological system can be considered as irreversible. Even if a clone with the same organizational principle (e.g. identical DNA-structure) could be developed, this would not mean that the former distinct system comes back into being. Events to which the self-organizing capacities of organisms, species or other complex systems can adapt, like minor injuries or changes in the physical environment are reversible. However, adaptation depends on import of negentropy into the organism, thereby increasing irreversible processes in its environment. Ecological principles, like those of sustainability and the precautionary principle can be defined with reference to the concept of reversibility.
== See also ==
== References == | Wikipedia/Irreversible_process_(thermodynamics) |
Topology of a transmembrane protein refers to locations of N- and C-termini of membrane-spanning polypeptide chain with respect to the inner or outer sides of the biological membrane occupied by the protein.
Several databases provide experimentally determined topologies of membrane proteins. They include Uniprot, TOPDB, OPM, and ExTopoDB. There is also a database of domains located conservatively on a certain side of membranes, TOPDOM.
Several computational methods were developed, with a limited success, for predicting transmembrane alpha-helices and their topology. Pioneer methods utilized the fact that membrane-spanning regions contain more hydrophobic residues than other parts of the protein, however applying different hydrophobic scales altered the prediction results. Later, several statistical methods were developed to improve the topography prediction and a special alignment method was introduced. According to the positive-inside rule, cytosolic loops near the lipid bilayer contain more positively-charged amino acids. Applying this rule resulted in the first topology prediction methods. There is also a negative-outside rule in transmembrane alpha-helices from single-pass proteins, although negatively charged residues are rarer than positively charged residues in transmembrane segments of proteins. As more structures were determined, machine learning algorithms appeared. Supervised learning methods are trained on a set of experimentally determined structures, however, these methods highly depend on the training set. Unsupervised learning methods are based on the principle that topology depends on the maximum divergence of the amino acid distributions in different structural parts. It was also shown that locking a segment location based on prior knowledge about the structure improves the prediction accuracy. This feature has been added to some of the existing prediction methods. The most recent methods use consensus prediction (i.e. they use several algorithms to determine the final topology) and automatically incorporate previously determined experimental informations. HTP database provides a collection of topologies that are computationally predicted for human transmembrane proteins.
Discrimination of signal peptides and transmembrane segments is an additional problem in topology prediction treated with a limited success by different methods. Both signal peptides and transmembrane segments contain hydrophobic regions which form α-helices. This causes the cross-prediction between them, which is a weakness of many transmembrane topology predictors. By predicting signal peptides and transmembrane helices simultaneously (Phobius), the errors caused by cross-prediction are reduced and the performance is substantially increased. Another feature used to increase the accuracy of the prediction is the homology (PolyPhobius).”
It is also possible to predict beta-barrel membrane proteins' topology.
== See also ==
Endomembrane system
Integral membrane protein
Protein topology
Structural biology
Transmembrane domain
== References == | Wikipedia/Transmembrane_topology |
ScienceDirect is a searchable web-based bibliographic database, which provides access to full texts of scientific and medical publications of the Dutch publisher Elsevier as well of several small academic publishers. It hosts over 18 million publications from more than 4,000 academic journals and 30,000 e-books. The access to the full-text requires subscription, while the bibliographic metadata are free to read. ScienceDirect was launched by Elsevier in March 1997.
== Usage ==
The journals are grouped into four main sections:
Physical Sciences and Engineering
Life Sciences
Health Sciences
Social Sciences and Humanities.
Article abstracts are freely available, and access to their full texts (in PDF and, for newer publications, also HTML) generally requires a subscription or pay-per-view purchase unless the content is freely available in open access.
Papers published under several open access licenses are available on ScienceDirect without cost. Access to the full-text pdfs of non-open access publications require either a subscription (to the specific journal rather than to the whole database) or per-article/book payment. Subscriptions to the overall content hosted on ScienceDirect, rather than to specific titles, are usually acquired through what is called a big deal. The other big five publishers have similar offers.
ScienceDirect also competes for audience with other large aggregators and hosts of scholarly communication content such as academic social network ResearchGate and open access repository arXiv, as well as with fully open access publishing venues and mega journals like PLOS.
ScienceDirect also carries Cell.
The search and bibliographic export options of ScienceDirect are very limited. For better search capabilities Elsevier provides via internet a paid-access database Scopus.
== See also ==
List of academic databases and search engines
Scopus
== References ==
== Further reading ==
Boukacem-Zeghmouri, Chérifa; Bador, Pascal; Lafouge, Thierry; Prost, Hélène (2016). "Relationships between consumption, publication and impact in French universities in a value perspective: A bibliometric analysis" (PDF). Scientometrics. 106: 263–280. doi:10.1007/s11192-015-1779-z. S2CID 8897085.
Emrani, Ebrahim; Moradi-Salari, A.; Jamali, Hamid R. (2013). "Usage data, e-journal selection and negotiations: Iranian consortium experience". hdl:10760/19670.
Gies, Ted (2018). "The Science Direct accessibility journey: A case study". Learned Publishing. 31: 69–76. doi:10.1002/leap.1142.
== External links ==
Official website | Wikipedia/Science_Direct |
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently undergo significant conformational changes to move a substance through the membrane. They are usually highly hydrophobic and aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction, although some of them (beta-barrels) can be also extracted using denaturing agents.
The peptide sequence that spans the membrane, or the transmembrane segment, is largely hydrophobic and can be visualized using the hydropathy plot. Depending on the number of transmembrane segments, transmembrane proteins can be classified as single-pass membrane proteins, or as multipass membrane proteins. Some other integral membrane proteins are called monotopic, meaning that they are also permanently attached to the membrane, but do not pass through it.
== Types ==
=== Classification by structure ===
There are two basic types of transmembrane proteins: alpha-helical and beta barrels. Alpha-helical proteins are present in the inner membranes of bacterial cells or the plasma membrane of eukaryotic cells, and sometimes in the bacterial outer membrane. This is the major category of transmembrane proteins. In humans, 27% of all proteins have been estimated to be alpha-helical membrane proteins.
Beta-barrel proteins are so far found only in outer membranes of gram-negative bacteria, cell walls of gram-positive bacteria, outer membranes of mitochondria and chloroplasts, or can be secreted as pore-forming toxins. All beta-barrel transmembrane proteins have simplest up-and-down topology, which may reflect their common evolutionary origin and similar folding mechanism.
In addition to the protein domains, there are unusual transmembrane elements formed by peptides. A typical example is gramicidin A, a peptide that forms a dimeric transmembrane β-helix. This peptide is secreted by gram-positive bacteria as an antibiotic. A transmembrane polyproline-II helix has not been reported in natural proteins. Nonetheless, this structure was experimentally observed in specifically designed artificial peptides.
=== Classification by topology ===
This classification refers to the position of the protein N- and C-termini on the different sides of the lipid bilayer. Types I, II, III and IV are single-pass molecules. Type I transmembrane proteins are anchored to the lipid membrane with a stop-transfer anchor sequence and have their N-terminal domains targeted to the endoplasmic reticulum (ER) lumen during synthesis (and the extracellular space, if mature forms are located on cell membranes). Type II and III are anchored with a signal-anchor sequence, with type II being targeted to the ER lumen with its C-terminal domain, while type III have their N-terminal domains targeted to the ER lumen. Type IV is subdivided into IV-A, with their N-terminal domains targeted to the cytosol and IV-B, with an N-terminal domain targeted to the lumen. The implications for the division in the four types are especially manifest at the time of translocation and ER-bound translation, when the protein has to be passed through the ER membrane in a direction dependent on the type.
== 3D structure ==
Membrane protein structures can be determined by X-ray crystallography, electron microscopy or NMR spectroscopy. The most common tertiary structures of these proteins are transmembrane helix bundle and beta barrel. The portion of the membrane proteins that are attached to the lipid bilayer (see annular lipid shell) consist mostly of hydrophobic amino acids.
Membrane proteins which have hydrophobic surfaces, are relatively flexible and are expressed at relatively low levels. This creates difficulties in obtaining enough protein and then growing crystals. Hence, despite the significant functional importance of membrane proteins, determining atomic resolution structures for these proteins is more difficult than globular proteins. As of January 2013 less than 0.1% of protein structures determined were membrane proteins despite being 20–30% of the total proteome. Due to this difficulty and the importance of this class of proteins methods of protein structure prediction based on hydropathy plots, the positive inside rule and other methods have been developed.
== Thermodynamic stability and folding ==
=== Stability of alpha-helical transmembrane proteins ===
Transmembrane alpha-helical (α-helical) proteins are unusually stable judging from thermal denaturation studies, because they do not unfold completely within the membranes (the complete unfolding would require breaking down too many α-helical H-bonds in the nonpolar media). On the other hand, these proteins easily misfold, due to non-native aggregation in membranes, transition to the molten globule states, formation of non-native disulfide bonds, or unfolding of peripheral regions and nonregular loops that are locally less stable.
It is also important to properly define the unfolded state. The unfolded state of membrane proteins in detergent micelles is different from that in the thermal denaturation experiments. This state represents a combination of folded hydrophobic α-helices and partially unfolded segments covered by the detergent. For example, the "unfolded" bacteriorhodopsin in SDS micelles has four transmembrane α-helices folded, while the rest of the protein is situated at the micelle-water interface and can adopt different types of non-native amphiphilic structures. Free energy differences between such detergent-denatured and native states are similar to stabilities of water-soluble proteins (< 10 kcal/mol).
=== Folding of α-helical transmembrane proteins ===
Refolding of α-helical transmembrane proteins in vitro is technically difficult. There are relatively few examples of the successful refolding experiments, as for bacteriorhodopsin. In vivo, all such proteins are normally folded co-translationally within the large transmembrane translocon. The translocon channel provides a highly heterogeneous environment for the nascent transmembrane α-helices. A relatively polar amphiphilic α-helix can adopt a transmembrane orientation in the translocon (although it would be at the membrane surface or unfolded in vitro), because its polar residues can face the central water-filled channel of the translocon. Such mechanism is necessary for incorporation of polar α-helices into structures of transmembrane proteins. The amphiphilic helices remain attached to the translocon until the protein is completely synthesized and folded. If the protein remains unfolded and attached to the translocon for too long, it is degraded by specific "quality control" cellular systems.
=== Stability and folding of beta-barrel transmembrane proteins ===
Stability of beta barrel (β-barrel) transmembrane proteins is similar to stability of water-soluble proteins, based on chemical denaturation studies. Some of them are very stable even in chaotropic agents and high temperature. Their folding in vivo is facilitated by water-soluble chaperones, such as protein Skp. It is thought that β-barrel membrane proteins come from one ancestor even having different number of sheets which could be added or doubled during evolution. Some studies show a huge sequence conservation among different organisms and also conserved amino acids which hold the structure and help with folding.
== 3D structures ==
=== Light absorption-driven transporters ===
Bacteriorhodopsin-like proteins including rhodopsin (see also opsin)
Bacterial photosynthetic reaction centres and photosystems I and II
Light-harvesting complexes from bacteria and chloroplasts
=== Oxidoreduction-driven transporters ===
Transmembrane cytochrome b-like proteins: coenzyme Q - cytochrome c reductase (cytochrome bc1 ); cytochrome b6f complex; formate dehydrogenase, respiratory nitrate reductase; succinate - coenzyme Q reductase (fumarate reductase); and succinate dehydrogenase. See electron transport chain.
Cytochrome c oxidases from bacteria and mitochondria
=== Electrochemical potential-driven transporters ===
Proton or sodium translocating F-type and V-type ATPases
=== P-P-bond hydrolysis-driven transporters ===
P-type calcium ATPase (five different conformations)
Calcium ATPase regulators phospholamban and sarcolipin
ABC transporters
General secretory pathway (Sec) translocon (preprotein translocase SecY)
=== Porters (uniporters, symporters, antiporters) ===
Mitochondrial carrier proteins
Major Facilitator Superfamily (Glycerol-3-phosphate transporter, Lactose permease, and Multidrug transporter EmrD)
Resistance-nodulation-cell division (multidrug efflux transporter AcrB, see multidrug resistance)
Dicarboxylate/amino acid:cation symporter (proton glutamate symporter)
Monovalent cation/proton antiporter (Sodium/proton antiporter 1 NhaA)
Neurotransmitter sodium symporter
Ammonia transporters
Drug/Metabolite Transporter (small multidrug resistance transporter EmrE - the structures are retracted as erroneous)
=== Alpha-helical channels including ion channels ===
Voltage-gated ion channel like, including potassium channels KcsA and KvAP, and inward-rectifier potassium ion channel Kirbac
Large-conductance mechanosensitive channel, MscL
Small-conductance mechanosensitive ion channel (MscS)
CorA metal ion transporters
Ligand-gated ion channel of neurotransmitter receptors (acetylcholine receptor)
Aquaporins
Chloride channels
Outer membrane auxiliary proteins (polysaccharide transporter) - α-helical transmembrane proteins from the outer bacterial membrane
=== Enzymes ===
Methane monooxygenase
Rhomboid protease
Disulfide bond formation protein (DsbA-DsbB complex)
=== Proteins with single transmembrane alpha-helices ===
Subunits of T cell receptor complex
Cytochrome c nitrite reductase complex
Glycophorin A dimer
Inovirus (filamentous phage) major coat protein
Pilin
Pulmonary surfactant-associated protein
Monoamine oxidases A and B
Fatty acid amide hydrolase
Cytochrome P450 oxidases
Corticosteroid 11β-dehydrogenases .
Signal Peptide Peptidase
=== Beta-barrels composed of a single polypeptide chain ===
Beta barrels from eight beta-strands and with "shear number" of ten (n=8, S=10). They include:
OmpA-like transmembrane domain (OmpA)
Virulence-related outer membrane protein family (OmpX)
Outer membrane protein W family (OmpW)
Antimicrobial peptide resistance and lipid A acylation protein family (PagP)
Lipid A deacylase PagL
Opacity family porins (NspA)
Autotransporter domain (n=12,S=14)
FadL outer membrane protein transport family, including Fatty acid transporter FadL (n=14,S=14)
General bacterial porin family, known as trimeric porins (n=16,S=20)
Maltoporin, or sugar porins (n=18,S=22)
Nucleoside-specific porin (n=12,S=16)
Outer membrane phospholipase A1(n=12,S=16)
TonB-dependent receptors and their plug domain. They are ligand-gated outer membrane channels (n=22,S=24), including cobalamin transporter BtuB, Fe(III)-pyochelin receptor FptA, receptor FepA, ferric hydroxamate uptake receptor FhuA, transporter FecA, and pyoverdine receptor FpvA
Outer membrane protein OpcA family (n=10,S=12) that includes outer membrane protease OmpT and adhesin/invasin OpcA protein
Outer membrane protein G porin family (n=14,S=16)
Note: n and S are, respectively, the number of beta-strands and the "shear number" of the beta-barrel
=== Beta-barrels composed of several polypeptide chains ===
Trimeric autotransporter (n=12,S=12)
Outer membrane efflux proteins, also known as trimeric outer membrane factors (n=12,S=18) including TolC and multidrug resistance proteins
MspA porin (octamer, n=S=16) and α-hemolysin (heptamer n=S=14) . These proteins are secreted.
== See also ==
Membrane topology
Transmembrane domain
Transmembrane receptors
== References == | Wikipedia/Integral_polytopic_protein |
Inner nuclear membrane proteins (INM proteins) are membrane proteins that are embedded in or associated with the inner membrane of the nuclear envelope. There are about 60 INM proteins, most of which are poorly characterized with respect to structure and function. Among the few well-characterized INM proteins are lamin B receptor (LBR), lamina-associated polypeptide 1 (LAP1), lamina-associated polypeptide-2 (LAP2), emerin and MAN1.
== Common structural features ==
Several integral nuclear membrane proteins of different size and structure have been identified. It is proposed that they share some structural features with respect to nucleoplasmic domain(s) and lipid-soluble domain(s). Some INM proteins contain common protein domain structures, and can thus be categorised into known protein domain families. These include the LEM-, SUN-, and KASH-domain families. Members of the LEM-domain family play a part in chromatin organisation . SUN- and KASH-domains participate in linking the cytoskeleton and nucleoskeleton through the LINC complex.
== Function ==
Lamins and chromatin found at the nuclear envelope are organised with the assistance of proteins embedded in the INM. INM proteins also aid in organization of nuclear pore complexes (NPCs). The protein mPom121 is targeted to the INM and is necessary for NPC formation. Proteins containing the LEM domain, such as emerin, LAP2β and MAN1, seem to have a number of roles. They interact with the barrier-to-autointegration factor (BAF). and help to repress gene expression, both by tethering specific genomic regions to the nuclear periphery, and by interaction with histone deacetylase (HDAC) 3.
== Synthesis and translocation ==
There are several proteins associated with the inner nuclear membrane. It is likely that the majority of them are also associated with the nuclear lamina. Some may interact directly with the nuclear lamina, and some may be associated with it through scaffold proteins. All INM proteins are arranged such that their N-termini is facing the nucleoplasm and targeted by various kinases. They are synthesized in one of three places; in the cytoplasm, the cytoplasmic ER, or the outer nuclear membrane. All require localisation to the INM. Since the outer nuclear membrane is continuous with the endoplasmic reticulum it is possible that the inner nuclear membrane proteins are translated on the rough endoplasmic reticulum, whereby the proteins move into the nucleus by lateral diffusion through a nuclear pore. In this model, proteins diffuse freely from the ER to the inner nuclear membrane, where association with nuclear lamina or chromatin immobilizes them. A nuclear localisation signal is not sufficient to target a protein to the INM, and the N-terminal domain of LBR cannot translocate into the nuclear lumen if its size is increased from 22 to approximately 70 kDa, supporting this view. Current opinion is that INM proteins synthesised in the cytoplasm are transported to the INM through nuclear pore complexes (NPC).
== Potential role in cell differentiation ==
It has been proposed that chromatin-binding/modifying proteins embedded within the inner nuclear membrane may be central in determining the identity of newly differentiated cells. The nucleoplasmic domains of such proteins can interact with chromatin to create a scaffold and restrict the conformation of chromosomes within three dimensions. Such inner-nuclear-membrane proteins (INMs) may function simply by restricting the movement of bound chromatin, by recruiting chromatin-remodeling proteins, or through inherent enzyme activity. INM:chromatin interactions causes some segments of chromatin to be more exposed to the nucleoplasm than others.
Once INM:chromatin interactions have been established following formation of the nuclear envelope, soluble nuclear proteins may bind to exposed chromosomal segments. Such proteins could include enzymes that modify histones—such as methylases and acetylases—which act to alter the three-dimensional conformation of chromatin, as well as DNA binding proteins—such as helicases, gyrases, and transcription factors—that are involved in unwinding/looping DNA and/or recruiting RNAP holoenzyme. This will promote the transcription of some genes and down-regulate or prevent transcription of others. Thus, the nuclear scaffold places limits on what genes can and can not be expressed within a given cell and, hence, may serve a basis for cell identity.
Once all regulatory proteins, etc. have been synthesized and the scaffold has been established, the cell has attained its own specific expression profile. This allows it to synthesize cell-specific enzymes and receptors characteristic of its particular function. The nuclear scaffold is predicted to be relatively permanent for a given cell type, but induction of a signaling pathway—by ligand binding, cell:cell contact, or some other mechanism—can temporarily shift the expression profile. When such a signal changes expression of genes coding for INM or a chromatin-modifying enzymes, it can induce differentiation in to a different cell type. Thus, the Nuclear Scaffold Theory predicts that symmetric cell division occurs when a daughter cell contains the same complement of INMs as the parent cell. Conversely, asymmetric cell division is expected to result in parent and daughter cells with different INM profiles.
The INM profile of closely related cells (e.g., CD4+ TH1 and TH2 helper T-cells) is expected to be more similar than for cells that are more distantly related (e.g., T-cells and B-cells). The degree of INM complementarity is expected to be roughly proportional to the degree of relatedness (e.g., % complementarity to TH1 helper T-cells will be: TH2 > CD8+ > B-cell > Erythrocyte > cardiomyocyte). Some cells that are very closely related may have similar INMs, but transient changes in expression—e.g., in response to extracellular signals—could possibly lead to more permanent changes in expression profile by altering transcription rates for chromatin modifying enzymes, transcriptional modulators, or other regulatory proteins.
== Examples ==
Emerin
Lamina-associated polypeptides 1 and 2 (LAP1, LAP2)
Lamin B receptor (LBR)
MAN1
Nurim
Dpy19L1 to L4
== Posttranslational modifications ==
Posttranslational modifications of INM proteins play a critical role in their functional modulation. For example, lamin B receptor, lamina-associated polypeptide 1 and lamina-associated polypeptide 2 are targets for different protein kinases. Arginine and serine residues phosphorylation control LBR's interaction with other subunits of the LBR complex and was proposed to modulate the interaction with chromatin.
== Disease ==
=== Laminopathies ===
The wide array of diseases involving lamins and their associated inner nuclear membrane proteins are collectively called laminopathies. Mutations in the gene EDM, encoding the INM protein emerin may be the cause of X-linked Emery–Dreifuss muscular dystrophy. As mutations in lamins cause the autosomal dominant form of Emery–Dreifuss muscular dystrophy, and lamins and emerin are known to interact, it has been hypothesised that muscle disease is caused by a structural defect in the nuclear envelope brought on by dysfunction in one of these proteins. Mutations in the gene LBR, encoding lamin B receptor, causes Pelger-Hüet anomaly.
=== Cancer ===
Tumor cells often show an aberrant nuclear structure, which is used by pathologists in diagnostics. As changes in the nuclear envelope correspond to functional changes in the nucleus, morphological changes in the nucleus may be involved in carcinogenesis. The regulatory functions of inner nuclear membrane proteins strongly suggest this possibility.
== See also ==
Integral membrane protein
Laminopathy
Transmembrane protein
== References == | Wikipedia/Inner_nuclear_membrane_proteins |
In molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other proteins or RNA. IDPs range from fully unstructured to partially structured and include random coil, molten globule-like aggregates, or flexible linkers in large multi-domain proteins. They are sometimes considered as a separate class of proteins along with globular, fibrous and membrane proteins.
IDPs are a very large and functionally important class of proteins. They are most numerous in eukaryotes, with an estimated 30-40% of residues in the eukaryotic proteome located in disordered regions. Disorder is present in around 70% of proteins, either in the form of disordered tails or flexible linkers. Proteins can also be entirely disordered and lack a defined secondary and/or tertiary structure. Their discovery has disproved the idea that three-dimensional structures of proteins must be fixed to accomplish their biological functions. For example, IDPs have been identified to participate in weak multivalent interactions that are highly cooperative and dynamic, lending them importance in DNA regulation and in cell signaling. Many IDPs can also adopt a fixed three-dimensional structure after binding to other macromolecules. Overall, IDPs are different from structured proteins in many ways and tend to have distinctive function, structure, sequence, interactions, evolution and regulation.
== History ==
In the 1930s-1950s, the first protein structures were solved by protein crystallography. These early structures suggested that a fixed three-dimensional structure might be generally required to mediate biological functions of proteins. These publications solidified the central dogma of molecular biology in that the amino acid sequence of a protein determines its structure which, in turn, determines its function. In 1950, Karush wrote about 'Configurational Adaptability' contradicting this assumption. He was convinced that proteins have more than one configuration at the same energy level and can choose one when binding to other substrates. In the 1960s, Levinthal's paradox suggested that the systematic conformational search of a long polypeptide is unlikely to yield a single folded protein structure on biologically relevant timescales (i.e. microseconds to minutes). Curiously, for many (small) proteins or protein domains, relatively rapid and efficient refolding can be observed in vitro. As stated in Anfinsen's Dogma from 1973, the fixed 3D structure of these proteins is uniquely encoded in its primary structure (the amino acid sequence), is kinetically accessible and stable under a range of (near) physiological conditions, and can therefore be considered as the native state of such "ordered" proteins.
During the subsequent decades, however, many large protein regions could not be assigned in x-ray datasets, indicating that they occupy multiple positions, which average out in electron density maps. The lack of fixed, unique positions relative to the crystal lattice suggested that these regions were "disordered". Nuclear magnetic resonance spectroscopy of proteins also demonstrated the presence of large flexible linkers and termini in many solved structural ensembles.
In 2001, Dunker questioned whether the newly found information was ignored for 50 years with more quantitative analyses becoming available in the 2000s. In the 2010s it became clear that IDPs are common among disease-related proteins, such as alpha-synuclein and tau.
== Abundance ==
It is now generally accepted that proteins exist as an ensemble of similar structures with some regions more constrained than others. IDPs occupy the extreme end of this spectrum of flexibility and include proteins of considerable local structure tendency or flexible multidomain assemblies.
Intrinsic disorder is particularly elevated among proteins that regulate chromatin and transcription, and bioinformatic predictions indicate that is more common in genomes and proteomes than in known structures in the protein database. Based on DISOPRED2 prediction, long (>30 residue) disordered segments occur in 2.0% of archaean, 4.2% of eubacterial and 33.0% of eukaryotic proteins, including certain disease-related proteins.
== Biological roles ==
Highly dynamic disordered regions of proteins have been linked to functionally important phenomena such as allosteric regulation and enzyme catalysis. Many disordered proteins have the binding affinity with their receptors regulated by post-translational modification, thus it has been proposed that the flexibility of disordered proteins facilitates the different conformational requirements for binding the modifying enzymes as well as their receptors. Intrinsic disorder is particularly enriched in proteins implicated in cell signaling and transcription, as well as chromatin remodeling functions. Genes that have recently been born de novo tend to have higher disorder. In animals, genes with high disorder are lost at higher rates during evolution.
=== Flexible linkers ===
Disordered regions are often found as flexible linkers or loops connecting domains. Linker sequences vary greatly in length but are typically rich in polar uncharged amino acids. Flexible linkers allow the connecting domains to freely twist and rotate to recruit their binding partners via protein domain dynamics. They also allow their binding partners to induce larger scale conformational changes by long-range allostery. The flexible linker of FBP25 which connects two domains of FKBP25 is important for the binding of FKBP25 with DNA.
=== Linear motifs ===
Linear motifs are short disordered segments of proteins that mediate functional interactions with other proteins or other biomolecules (RNA, DNA, sugars etc.). Many roles of linear motifs are associated with cell regulation, for instance in control of cell shape, subcellular localisation of individual proteins and regulated protein turnover. Often, post-translational modifications such as phosphorylation tune the affinity (not rarely by several orders of magnitude) of individual linear motifs for specific interactions. Relatively rapid evolution and a relatively small number of structural restraints for establishing novel (low-affinity) interfaces make it particularly challenging to detect linear motifs but their widespread biological roles and the fact that many viruses mimick/hijack linear motifs to efficiently recode infected cells underlines the timely urgency of research on this very challenging and exciting topic.
=== Pre-structured motifs ===
Unlike globular proteins, IDPs do not have spatially-disposed active pockets. Fascinatingly, 80% of target-unbound IDPs (~4 dozens) subjected to detailed structural characterization by NMR possess linear motifs termed PresMos (pre-structured motifs) that are transient secondary structural elements primed for target recognition. In several cases it has been demonstrated that these transient structures become full and stable secondary structures, e.g., helices, upon target binding. Hence, PresMos are the putative active sites in IDPs.
=== Coupled folding and binding ===
Many unstructured proteins undergo transitions to more ordered states upon binding to their targets (e.g. molecular recognition features (MoRFs)). The coupled folding and binding may be local, involving only a few interacting residues, or it might involve an entire protein domain. It was recently shown that the coupled folding and binding allows the burial of a large surface area that would be possible only for fully structured proteins if they were much larger. Moreover, certain disordered regions might serve as "molecular switches" in regulating certain biological function by switching to ordered conformation upon molecular recognition like small molecule-binding, DNA/RNA binding, ion interactions etc.
The ability of disordered proteins to bind, and thus to exert a function, shows that stability is not a required condition. Many short functional sites, for example short linear motifs are over-represented in disordered proteins. Disordered proteins and short linear motifs are particularly abundant in many RNA viruses such as Hendra virus, HCV, HIV-1 and human papillomaviruses. This enables such viruses to overcome their informationally limited genomes by facilitating binding, and manipulation of, a large number of host cell proteins.
=== Disorder in the bound state (fuzzy complexes) ===
Intrinsically disordered proteins can retain their conformational freedom even when they bind specifically to other proteins. The structural disorder in bound state can be static or dynamic. In fuzzy complexes structural multiplicity is required for function and the manipulation of the bound disordered region changes activity. The conformational ensemble of the complex is modulated via post-translational modifications or protein interactions. Specificity of DNA binding proteins often depends on the length of fuzzy regions, which is varied by alternative splicing. Some fuzzy complexes may exhibit high binding affinity, although other studies showed different affinity values for the same system in a different concentration regime.
== Structural aspects ==
Intrinsically disordered proteins adapt a dynamic range of rapidly interchanging conformations in vivo according to the cell's conditions, creating a structural or conformational ensemble.
Therefore, their structures are strongly function-related. However, only few proteins are fully disordered in their native state. Disorder is mostly found in intrinsically disordered regions (IDRs) within an otherwise well-structured protein. The term intrinsically disordered protein (IDP) therefore includes proteins that contain IDRs as well as fully disordered proteins.
The existence and kind of protein disorder is encoded in its amino acid sequence. In general, IDPs are characterized by a low content of bulky hydrophobic amino acids and a high proportion of polar and charged amino acids, usually referred to as low hydrophobicity. This property leads to good interactions with water. Furthermore, high net charges promote disorder because of electrostatic repulsion resulting from equally charged residues. Thus disordered sequences cannot sufficiently bury a hydrophobic core to fold into stable globular proteins. In some cases, hydrophobic clusters in disordered sequences provide the clues for identifying the regions that undergo coupled folding and binding (refer to biological roles). Many disordered proteins reveal regions without any regular secondary structure. These regions can be termed as flexible, compared to structured loops. While the latter are rigid and contain only one set of Ramachandran angles, IDPs involve multiple sets of angles. The term flexibility is also used for well-structured proteins, but describes a different phenomenon in the context of disordered proteins. Flexibility in structured proteins is bound to an equilibrium state, while it is not so in IDPs. Many disordered proteins also reveal low complexity sequences, i.e. sequences with over-representation of a few residues. While low complexity sequences are a strong indication of disorder, the reverse is not necessarily true, that is, not all disordered proteins have low complexity sequences. Disordered proteins have a low content of predicted secondary structure.
Due to the disordered nature of these proteins, topological approaches have been developed to search for conformational patterns in their dynamics. For instance, circuit topology has been applied to track the dynamics of disordered protein domains. By employing a topological approach, one can categorize motifs according to their topological buildup and the timescale of their formation.
A common aspect of IDP structural ensembles is the ability or tendency to fold upon an interaction to a binding partner in the cell. Examples of IDP folding in a binding context are binding-coupled folding, and formation of fuzzy complexes. However, it is also possible for proteins to remain entirely disordered in a binding scenario.
== Experimental validation ==
IDPs can be validated in several contexts. Most approaches for experimental validation of IDPs are restricted to extracted or purified proteins while some new experimental strategies aim to explore in vivo conformations and structural variations of IDPs inside intact living cells and systematic comparisons between their dynamics in vivo and in vitro.
=== In vivo approaches ===
The first direct evidence for in vivo persistence of intrinsic disorder has been achieved by in-cell NMR upon electroporation of a purified IDP and recovery of cells to an intact state.
Larger-scale in vivo validation of IDR predictions is now possible using biotin 'painting'.
=== In vitro approaches ===
Intrinsically unfolded proteins, once purified, can be identified by various experimental methods. The primary method to obtain information on disordered regions of a protein is NMR spectroscopy. The lack of electron density in X-ray crystallographic studies may also be a sign of disorder.
Folded proteins have a high density (partial specific volume of 0.72-0.74 mL/g) and commensurately small radius of gyration. Hence, unfolded proteins can be detected by methods that are sensitive to molecular size, density or hydrodynamic drag, such as size exclusion chromatography, analytical ultracentrifugation, small angle X-ray scattering (SAXS), and measurements of the diffusion constant. Unfolded proteins are also characterized by their lack of secondary structure, as assessed by far-UV (170–250 nm) circular dichroism (esp. a pronounced minimum at ~200 nm) or infrared spectroscopy. Unfolded proteins also have exposed backbone peptide groups exposed to solvent, so that they are readily cleaved by proteases, undergo rapid hydrogen-deuterium exchange and exhibit a small dispersion (<1 ppm) in their 1H amide chemical shifts as measured by NMR. (Folded proteins typically show dispersions as large as 5 ppm for the amide protons.) Recently, new methods including fast parallel proteolysis (FASTpp) have been introduced, which allow to determine the fraction folded/disordered without the need for purification. Even subtle differences in the stability of missense mutations, protein partner binding and (self)polymerisation-induced folding of (e.g.) coiled-coils can be detected using FASTpp as recently demonstrated using the tropomyosin-troponin protein interaction. Fully unstructured protein regions can be experimentally validated by their hypersusceptibility to proteolysis using short digestion times and low protease concentrations.
Bulk methods to study IDP structure and dynamics include SAXS for ensemble shape information, NMR for atomistic ensemble refinement, fluorescence for visualising molecular interactions and conformational transitions, x-ray crystallography to highlight more mobile regions in otherwise rigid protein crystals, cryo-EM to reveal less fixed parts of proteins, light scattering to monitor size distributions of IDPs or their aggregation kinetics, NMR chemical shift and circular dichroism to monitor secondary structure of IDPs.
Single-molecule methods to study IDPs include spFRET to study conformational flexibility of IDPs and the kinetics of structural transitions, optical tweezers for high-resolution insights into the ensembles of IDPs and their oligomers or aggregates, nanopores to reveal global shape distributions of IDPs, magnetic tweezers to study structural transitions for long times at low forces, high-speed atomic force microscopy (AFM) to visualise the spatio-temporal flexibility of IDPs directly.
== Disorder annotation ==
Intrinsic disorder can be either annotated from experimental information or predicted with specialized software. Disorder prediction algorithms can predict intrinsic disorder (ID) propensity with high accuracy (approaching around 80%) based on primary sequence composition, similarity to unassigned segments in protein x-ray datasets, flexible regions in NMR studies and physico-chemical properties of amino acids.
=== Disorder databases ===
Databases have been established to annotate protein sequences with intrinsic disorder information. The DisProt database contains a collection of manually curated protein segments which have been experimentally determined to be disordered. MobiDB is a database combining experimentally curated disorder annotations (e.g. from DisProt) with data derived from missing residues in X-ray crystallographic structures and flexible regions in NMR structures.
=== Predicting IDPs by sequence ===
Separating disordered from ordered proteins is essential for disorder prediction. One of the first steps to find a factor that distinguishes IDPs from non-IDPs is to specify biases within the amino acid composition. The following hydrophilic, charged amino acids A, R, G, Q, S, P, E and K have been characterized as disorder-promoting amino acids, while order-promoting amino acids W, C, F, I, Y, V, L, and N are hydrophobic and uncharged. The remaining amino acids H, M, T and D are ambiguous, found in both ordered and unstructured regions. A more recent analysis ranked amino acids by their propensity to form disordered regions as follows (order promoting to disorder promoting): W, F, Y, I, M, L, V, N, C, T, A, G, R, D, H, Q, K, S, E, P. As it can be seen from the list, small, charged, hydrophilic residues often promote disorder, while large and hydrophobic residues promote order.
This information is the basis of most sequence-based predictors. Regions with little to no secondary structure, also known as NORS (no regular secondary structure) regions, and low-complexity regions can easily be detected. However, not all disordered proteins contain such low complexity sequences.
=== Prediction methods ===
Determining disordered regions from biochemical methods is very costly and time-consuming. Due to the variable nature of IDPs, only certain aspects of their structure can be detected, so that a full characterization requires a large number of different methods and experiments. This further increases the expense of IDP determination. In order to overcome this obstacle, computer-based methods are created for predicting protein structure and function. It is one of the main goals of bioinformatics to derive knowledge by prediction. Predictors for IDP function are also being developed, but mainly use structural information such as linear motif sites. There are different approaches for predicting IDP structure, such as neural networks or matrix calculations, based on different structural and/or biophysical properties.
Many computational methods exploit sequence information to predict whether a protein is disordered. Notable examples of such software include IUPRED and Disopred. Different methods may use different definitions of disorder. Meta-predictors show a new concept, combining different primary predictors to create a more competent and exact predictor.
Due to the different approaches of predicting disordered proteins, estimating their relative accuracy is fairly difficult. For example, neural networks are often trained on different datasets. The disorder prediction category is a part of biannual CASP experiment that is designed to test methods according accuracy in finding regions with missing 3D structure (marked in PDB files as REMARK465, missing electron densities in X-ray structures).
== Disorder and disease ==
Intrinsically unstructured proteins have been implicated in a number of diseases. Aggregation of misfolded proteins is the cause of many synucleinopathies and toxicity as those proteins start binding to each other randomly and can lead to cancer or cardiovascular diseases. Thereby, misfolding can happen spontaneously because millions of copies of proteins are made during the lifetime of an organism. The aggregation of the intrinsically unstructured protein α-synuclein is thought to be responsible. The structural flexibility of this protein together with its susceptibility to modification in the cell leads to misfolding and aggregation. Genetics, oxidative and nitrative stress as well as mitochondrial impairment impact the structural flexibility of the unstructured α-synuclein protein and associated disease mechanisms. Many key tumour suppressors have large intrinsically unstructured regions, for example p53 and BRCA1. These regions of the proteins are responsible for mediating many of their interactions. Taking the cell's native defense mechanisms as a model drugs can be developed, trying to block the place of noxious substrates and inhibiting them, and thus counteracting the disease.
== Computer simulations ==
Owing to high structural heterogeneity, NMR/SAXS experimental parameters obtained will be an average over a large number of highly diverse and disordered states (an ensemble of disordered states). Hence, to understand the structural implications of these experimental parameters, there is a necessity for accurate representation of these ensembles by computer simulations. All-atom molecular dynamic simulations can be used for this purpose but their use is limited by the accuracy of current force-fields in representing disordered proteins. Nevertheless, some force-fields have been explicitly developed for studying disordered proteins by optimising force-field parameters using available NMR data for disordered proteins. (examples are CHARMM 22*, CHARMM 32, Amber ff03* etc.)
MD simulations restrained by experimental parameters (restrained-MD) have also been used to characterise disordered proteins. In principle, one can sample the whole conformational space given an MD simulation (with accurate Force-field) is run long enough. Because of very high structural heterogeneity, the time scales that needs to be run for this purpose are very large and are limited by computational power. However, other computational techniques such as accelerated-MD simulations, replica exchange simulations, metadynamics, multicanonical MD simulations, or methods using coarse-grained representation with implicit and explicit solvents have been used to sample broader conformational space in smaller time scales.
Moreover, various protocols and methods of analyzing IDPs, such as studies based on quantitative analysis of GC content in genes and their respective chromosomal bands, have been used to understand functional IDP segments.
== See also ==
IDPbyNMR
DisProt database
MobiDB database
Molten globule
Prion
Random coil
Dark proteome
== References ==
== External links ==
Intrinsically disordered protein at Proteopedia
MobiDB: a comprehensive database of intrinsic protein disorder annotations
IDEAL - Intrinsically Disordered proteins with Extensive Annotations and Literature Archived 2020-05-02 at the Wayback Machine
D2P2 Database of Disordered Protein Predictions
Gallery of images of intrinsically disordered proteins
First IDP journal covering all topics of IDP research
IDP Journal
Database of experimentally validated IDPs
IDP ensemble database Archived 2018-03-10 at the Wayback Machine | Wikipedia/Disordered_protein |
Nature Reviews Drug Discovery is a monthly peer-reviewed review journal published by Nature Portfolio. It was established in 2002 and covers drug discovery and development. The editor-in-chief is Peter Kirkpatrick. According to the Journal Citation Reports, the journal has a 2021 impact factor of 112.288, ranking it 1st out of 158 journals in the category "Biotechnology & Applied Microbiology" and 1st out of 279 journals in the category "Pharmacology & Pharmacy".
Reviews are commissioned to specialists and supplemented with glossary explanations for non-specialist readers and illustrated with figures drawn by Nature's in-house art editors. Besides reviews, the journal publishes analysis articles based on existing datasets (e.g. metaanalysis), progress articles that focus on outstanding issues, and perspective articles—typically opinions or historical pieces.
== See also ==
Nature Biotechnology
Annual Review of Pharmacology and Toxicology
Pharmacological Reviews
== References ==
== External links ==
Official website | Wikipedia/Nature_Reviews_Drug_Discovery |
A single-pass membrane protein also known as single-spanning protein or bitopic protein is a transmembrane protein that spans the lipid bilayer only once. These proteins may constitute up to 50% of all transmembrane proteins, depending on the organism, and contribute significantly to the network of interactions between different proteins in cells, including interactions via transmembrane alpha helices. They usually include one or several water-soluble domains situated at the different sides of biological membranes, for example in single-pass transmembrane receptors. Some of them are small and serve as regulatory or structure-stabilizing subunits in large multi-protein transmembrane complexes, such as photosystems or the respiratory chain. More than 2300 single-pass membrane proteins were identified in the human genome.
== Topology-based classification ==
Bitopic proteins are classified into 4 types, depending on their transmembrane topology and location of the transmembrane helix in the amino acid sequence of the protein. According to Uniprot:
Type I: N-terminus on the extracellular side of the membrane; removed signal peptide
Type II: N-terminus on the cytoplasmic side of the membrane; transmembrane helix located close to the N-terminus, where it works as an anchor
Type III: N-terminus on the extracellular side of the membrane; no signal peptide
Type IV: N-terminus on the cytoplasmic side of the membrane; transmembrane helix located close to the C-terminus, where it works as an anchor
Hence type I proteins are anchored to the lipid membrane with a stop-transfer anchor sequence and have their N-terminal domains targeted to the ER lumen during synthesis. Type II and III are anchored with a signal-anchor sequence, with type II being targeted to the ER lumen with its C-terminal domain, while type III have their N-terminal domains targeted to the ER lumen.
== Structure ==
A single-pass transmembrane protein typically consists of three domains, the extracellular domain, the transmembrane domain, and the intracellular domain. The transmembrane domain is the smallest at around 25 amino acid residues and forms an alpha helix inserted into the membrane bilayer. The ECD is typically much larger than the ICD and is often globular, whereas many ICDs have relatively high disorder. Some proteins in this class function as monomers, but dimerization or higher-order oligomerization is common.
== Evolution ==
The number of single-pass transmembrane proteins in an organism's genome varies significantly. It is higher in eukaryotes than prokaryotes and in multicellular than unicellular organisms. The fraction of proteins in this class is larger in humans than in the model organisms Danio rerio (zebrafish) and Caenorhabditis elegans (nematode worms), suggesting that genes encoding these proteins have undergone expansion in the vertebrate and mammalian lineages.
== Databases ==
Membranome database is a database of bitopic proteins from several model organisms.
Bitopic proteins in OPM database
== References == | Wikipedia/Bitopic_protein |
Invertebrate zoology is the subdiscipline of zoology that consists of the study of invertebrates, animals without a backbone (a structure which is found only in fish, amphibians, reptiles, birds and mammals).
Invertebrates are a vast and very diverse group of animals that includes sponges, echinoderms, tunicates, numerous different phyla of worms, molluscs, arthropods and many additional phyla. Single-celled organisms or protists are usually not included within the same group as invertebrates.
== Subdivisions ==
Invertebrates represent 97% of all named animal species, and because of that fact, this subdivision of zoology has many further
subdivisions, including but not limited to:
Arthropodology - the study of arthropods, which includes
Arachnology - the study of spiders and other arachnids
Entomology - the study of insects
Carcinology - the study of crustaceans
Myriapodology - the study of centipedes, millipedes, and other myriapods
Cnidariology - the study of Cnidaria
Helminthology - the study of parasitic worms.
Malacology - the study of mollusks, which includes
Conchology - the study of Mollusk shells.
Limacology - the study of slugs.
Teuthology - the study of cephalopods.
Invertebrate paleontology - the study of fossil invertebrates
These divisions are sometimes further divided into more specific specialties. For example, within arachnology, acarology is the study of mites and ticks; within entomology, lepidoptery is the study of butterflies and moths, myrmecology is the study of ants and so on. Marine invertebrates are all those invertebrates that exist in marine habitats.
== History ==
=== Early Modern Era ===
In the early modern period starting in the late 16th century, invertebrate zoology saw growth in the number of publications made and improvement in the experimental practices associated with the field. (Insects are one of the most diverse groups of organisms on Earth. They play important roles in ecosystems, including pollination, natural enemies, saprophytes, and biological information transfer.)
One of the major works to be published in the area of zoology was Conrad Gessner's Historia animalium, which was published in numerous editions from 1551 to 1587. Though it was a work more generally addressing zoology in the large sense, it did contain information on insect life. Much of the information came from older works; Gessner restated the work of Pliny the Elder and Aristotle while mixing old knowledge of the natural history of insects with his own observations.
With the invention of the Microscope in 1599 came a new way of observing the small creatures that fall under the umbrella of invertebrate. Robert Hooke, who worked out of the Royal Society in England, conducted observation of insects—including some of their larval forms—and other invertebrates, such as ticks. His Micrographia, published in 1665, included illustrations and written descriptions of the things he saw under the microscope.
Others also worked with the microscope following its acceptance as a scientific tool. Francesco Redi, an Italian physician and naturalist, used a microscope for observation of invertebrates, but is known for his work in disproving the theory of spontaneous generation. Redi managed to prove that flies did not spontaneously arise from rotting meat. He conducted controlled experiments and detailed observation of the fly life cycle in order to do so. Redi also worked in the description and illustration of parasites for both plants and animals.
Other men were also conducting research into pests and parasites at this time. Felix Plater, a Swiss physician, worked to differentiate between two types of tape worm. He also wrote descriptions of both the worms he observed and the effects these worms had on their hosts.
Following the publication of Francis Bacon's ideas about the value of experimentation in the sciences came a shift toward true experimental efforts in the biological sciences, including invertebrate zoology. Jan Swammerdam, a Dutch microscopist, supported an effort to work for a 'modern' science over blind belief in the work of ancient philosophers. He worked—like Redi—to disprove spontaneous generation using experimental techniques. Swammerdam also made a number of advancements in the study of anatomy and physiology. In the field of entomology, he conducted a number of dissections of insects and made detailed observations of the internal structures of these specimens. Swammerdam also worked on a classification of insects based on life histories; he managed to contribute to the literature proving that an egg, larva, pupa, and adult are indeed the same individual.
=== 18th and 19th centuries ===
In the 18th century, the study of invertebrates focused on the naming of species that were relevant to economic pursuits, such as agricultural pests. Entomology was changing in big ways very quickly, as many naturalists and zoologists were working with hexapods.
Work was also being done in the realm of parasitology and the study of worms. A French physician named Nicolas Andry de Bois-Regard determined that worms were the cause of some diseases. He also declared that worms do not spontaneously form within the animal or human gut; de Bois-Regard stated that there must be some kind of 'seed' which enters the body and contains the worm in some form. Antonio Vallisneri also worked with parasitic worms, specifically members of the genera Ascaris and Neoascaris. He found that these worms came from eggs. In addition, Vallisneri worked to elucidate the reproduction of insects, specifically the sawfly.
In 1735, the first edition of Carl Linnaeus' Systema Naturae was published; this work included information on both insects and intestinal worms. However, the tenth edition is considered the true starting point for the modern classification scheme for living things today. Linnaeus' universal system of classification made a system based on binomial nomenclature, but included higher levels of classification than simply the genus and species names. Systema Naturae was an investigation into the biodiversity on Earth. However, because it was based only on very few characters, the system developed by Linnaeus was an artificial one. The book also included descriptions of the organisms named inside of it.
In 1859, Charles Darwin's On the Origin of Species was published. In this book, he described his theory of evolution by natural selection. Both the work of Darwin and his contemporary, Alfred Russel Wallace —who was also working on the theory of evolution—were informed by the careful study of insects. In addition, Darwin collected many species of invertebrate during his time aboard HMS Beagle; many of the specimens collected were insects. Using these collections, he was able to study sexual dimorphism, geographic distribution of species, and mimicry; all of these concepts influenced Darwin's theory of evolution. Unfortunately, a firm popular belief in the immutability of species was a major hurdle in the acceptance of the theory.
=== 20th century ===
Classification in the twentieth century shifted toward a focus on evolutionary relationships over morphological description. The development of phylogenetics and systematics based on this study is credited to Willi Hennig, a German entomologist. In 1966, his Phylogenetic Systematics was published; inside, Hennig redefined the goals of systematic schemes for classifying living things. He proposed that the focus be on evolutionary relationships over similar morphological features. He also defined monophyly and included his ideas about hierarchical classification. Though Hennig did not include information on outgroup comparison, he was apparently aware of the practice, which is considered important to today's systematic research.
== Notable invertebrates ==
The Japanese spider crab (Arthropoda: Macrocheira kaempferi) is one of the world's largest arthropods. The Japanese spider crab is largest known species of crab and may live up to 100 years. With a leg span of that can reach four feet, it has the longest span of any arthropod. They are typically found in the Pacific waters near Japan on the bottom of the continental shelf.
The lion's mane jellyfish (Cnidaria: Cyanea capillata) is the largest known type of jellyfish. Their tentacles can reach up to 190 feet long, and they may have a bell diameter of almost 7 feet. These animals are usually found in cold northern Arctic waters and in the Northern portions of the Atlantic and Pacific Oceans.
The giant squid (Mollusca: Architeuthis dux) comes from the family Architeuthidae. These squid are both the largest known cephalopod and the largest known mollusc. They can grow to a length of about 45–50 feet long. They developed large eyes, the largest of any animal, to be able to detect small amounts of bioluminescence in the dark and deep ocean where they live.
== References ==
== External links ==
A Study Guide to Invertebrate Zoology ~ at Wikibooks
Online Dictionary of Invertebrate Zoology | Wikipedia/Invertebrate_zoology |
Invertebrate paleontology (also spelled invertebrate palaeontology) is sometimes described as invertebrate paleozoology or invertebrate paleobiology.
Whether it is considered to be a subfield of paleontology, paleozoology, or paleobiology, this discipline is the scientific study of prehistoric invertebrates by analyzing invertebrate fossils in the geologic record.
By invertebrates are meant the non-vertebrate creatures of the kingdom Animalia (or Metazoa) in the biotic domain of Eukaryota. By phyletic definition, these many-celled, sub-vertebrate animals lack a vertebral column, spinal column, vertebrae, backbone, or long, full-length notochord—in contrast to the vertebrates in the one phylum of Chordata.
Relatedly, invertebrates have never had a cartilaginous or boney internal skeleton, with its skeletal supports, gill slits, ribs and jaws. Finally, throughout geologic time, invertebrates have remained non-craniate creatures; that is, they never developed a cranium, nerve-chord brain, skull, or hard protective braincase (unlike many vertebrates).
== Invertebrate terminology in science ==
In the many decades since Jean-Baptiste de Lamarck, a pioneering biologist and evolutionist, first conceptualized and coined the category "Invertebrata" (between 1793 and 1801) and the term "Biology" (in 1802), zoology has come to recognize that the non-vertebrate category is not a scientifically valid, monophyletic taxon. Evolutionary biology and developmental biology (a.k.a. "evo-devo") now consider the term "Invertebrata" to be both polyphyletic and paraphyletic. Nevertheless, most earth science departments continue to employ this term; and paleontologists find it both useful and practical in evaluating fossil invertebrates and—consequently—invertebrate evolution.
However, there is one contemporary caveat: Paleobiologists and microbiologists in the 21st century no longer classify one-celled "animal-like" microbes either as invertebrates or as animals.
For example, the commonly fossilized foraminifera ("forams") and radiolarians—zooplankton both formerly grouped under either an animal phylum or animal sub-kingdom called Protozoa ("first animals")—are now placed in the kingdom or super-kingdom Protista or Protoctista (and thus called protists or protoctists).
Thus modern invertebrate paleontologists deal largely with fossils of this more strictly defined Animal Kingdom (excepting Phylum Chordata), Phylum Chordata being the exclusive focus of vertebrate paleontology. Protist fossils are then the main focus of micropaleontology, while plant fossils are the chief focus paleobotany. Together these four represent the traditional taxonomic divisions of paleontologic study.
=== Origins and modern evolution ===
== Invertebrate fossilization ==
When it comes to the fossil record, soft-bodied and minuscule invertebrates—such as hydras, jellies, flatworms, hairworms, nematodes, ribbon worms, rotifers and roundworms—are infrequently fossilized. As a result, paleontologists and other fossil hunters must often rely on trace fossils, microfossils, or chemofossil residue when scouting for these prehistoric creatures.
Hard-bodied and large invertebrates are much more commonly preserved; typically as sizeable macrofossils. These invertebrates are more frequently preserved because their hard parts fossilise more readily—for example, shell, armor, plates, tests, exoskeleton, jaws or teeth. In invertebrates, these parts are composed of silica (silicon dioxide), calcite or aragonite (both forms of calcium carbonate), chitin (a protein often infused with tricalcium phosphate), or keratin (an even-more complex protein), rather than the vertebrate bone (hydroxyapatite) or cartilage of fishes and land-dwelling tetrapods.
The chitinous jaws of annelids (such as the marine scolecodonts) are sometimes preserved as fossils; while many arthropods and inarticulate brachiopods have easily fossilized hard parts of calcite, chitin, or keratin. The most common and often-found macrofossils are the very hard calcareous shells of articulate brachiopods (that is, the everyday "lampshells") and of mollusks (such as the omnipresent clams, snails, mussels and oysters). On the other hand, shell-less slugs and non-tubiferous worms (for instance, earthworms) lack hard parts and therefore such organisms are poorly represented in the fossil record.
=== Taxonomy of commonly fossilised invertebrates ===
== Footnotes ==
== Further reading ==
Although these books are not footnoted in this article, the following are well-illustrated, well-organized—and often well-worn—guides to invertebrate (and sometimes other) fossils:
Paolo Arduini (1987), Simon and Schuster's Guide to Fossils (Old Tappan, New Jersey: Fireside), 320 pages. ISBN 0-671-63132-2.
James R. Beerbower (1968). Search for the Past: An Introduction to Paleontology (Englewood Cliffs, New Jersey: Prentice-Hall), 512 pages.
R. S. Boardman and others (1985). Fossil Invertebrates.
British Museum of Natural History (1969). British Palaeozoic Fossils (London, England: British Museum of Natural History).
Euan N. K. Clarkson (1998). Invertebrate Palaeontology and Evolution (London, England: Allen and Unwin), 468 pages. ISBN 978-0-632-05238-7.
Peter Doyle (1996), Understanding Fossils: An Introduction to Invertebrate Paleontology (Hoboken, New Jersey: John Wiley & Sons), 426 pages. ISBN 0-471-96351-8.
Carroll Lane Fenton and Mildred Adams Fenton (1958); updated by Patricia Vickers Rich and Thomas Hewitt Rich (1997). The Fossil Book: A Record of Prehistoric Life (Garden City, New York: Doubleday and Courier Dover Publishing), from 482 to 760 pages. ISBN 0-486-29371-8.
W. R. Hamilton and others (1974). A Guide to Minerals, Rocks and Fossils (London, England: Hamlyn Publishing Group Ltd.), 320 pages.
W. B. Harland (1967). The Fossil Record (London, England: Geological Society of London), 827 pages.
V. Lehmann and G. Hillmer (1983). Fossil Invertebrates (Cambridge, England: Cambridge University Press).
Harold L. Levin (1998), Ancient Invertebrates and Their Living Relatives (Boston: Prentice-Hall), 358 pages. ISBN 978-0-13-748955-8.
William H. Matthews III (1962). Fossils: An Introduction to Prehistoric Life (New York: Barnes & Noble), 337 pages.
Helmut Mayr (1992). A Guide to Fossils (New York: Longman, Harlow).
Raymond C. Moore and others (1952). Invertebrate Fossils (New York: McGraw-Hill), 776 pages. ISBN 0-07-043020-9.
J. W. Murray, editor (1985). Atlas of Invertebrate Macrofossils (Princeton: Princeton University Press), 256 pages.
Douglas Palmer (2004), Fossils (London, England: Dorling Kindersley).
Frank H. T. Rhodes and others (1962). Fossils: A Guide to Prehistoric Life (New York: Golden Nature Guide), 242 pages.
Henry Woodburn Shimer and Robert Rakes Shrock (1944/1983). Index Fossils of North America (Cambridge, Massachusetts: Massachusetts Institute of Technology Press), 837 pages.
Robert Rakes Shrock and W. H. Twenhofel (1953). Invertebrate Paleontology (New York: McGraw-Hill).
Ronald Singer (2000), Encyclopedia of Paleontology (London, England: Routledge), 1,467 pages. ISBN 1-884964-96-6.
Ida Thompson (1982/2004). National Audubon Society Field Guide to North American Fossils (New York: Alfred A. Knopf), 846 pages.
James W. Valentine (2004), On the Origins of Phyla (Chicago: University of Chicago Press). 608 pages. ISBN 0-226-84548-6. A discussion focusing on invertebrates during the Paleozoic era.
Cyril Walker and David Ward (2002). Smithsonian Handbook of Fossils (London, England: Dorling Kindersley), 320 pages.
== External links ==
A colorful, illustrated taxonomy of extinct and living invertebrate Metazoa by the University of California Museum of Paleontology.
The invertebrate fossil record illustrated colorfully for Metazoa provided by the U.C. Museum of Paleontology.
Educational and colorful introduction to the three domains of the Tree of Life – as well as to the topic of "Understanding Evolution" – sponsored by the U.C. Museum of Paleontology.
An introduction to fossils Archived 2009-09-30 at the Wayback Machine by The Paleontology Portal, a project of four American institutions funded by the National Science Foundation.
The introduction to invertebrate fossils provided by The Paleontology Portal.
Thousands of online pictures of invertebrate fossils. sponsored by the Peabody Museum at Yale University.
The taxonomy of the Metazoa Kingdom of animals provided by The Tree of Life Project.
Home site of the many volumes of the Treatise on Invertebrate Paleontology, a site sponsored by both The Paleontological Institute at the University of Kansas and the Geological Society of America. | Wikipedia/Invertebrate_paleontology |
Terrestrial animals are animals that live predominantly or entirely on land (e.g. cats, chickens, ants, most spiders), as compared with aquatic animals, which live predominantly or entirely in the water (e.g. fish, lobsters, octopuses), and semiaquatic animals, which rely on both aquatic and terrestrial habitats (e.g. platypus, most amphibians). Some groups of insects are terrestrial, such as ants, butterflies, earwigs, cockroaches, grasshoppers and many others, while other groups are partially aquatic, such as mosquitoes and dragonflies, which pass their larval stages in water.
Alternatively, terrestrial is used to describe animals that live on the ground, as opposed to arboreal animals that live in trees.
== Ecological subgroups ==
The term "terrestrial" is typically applied to species that live primarily on or in the ground, in contrast to arboreal species, who live primarily in trees, even though the latter are actually a specialized subgroup of the terrestrial fauna.
There are other less common terms that apply to specific subgroups of terrestrial animals:
Saxicolous creatures are rock dwelling. "Saxicolous" is derived from the Latin word saxum, meaning a rock.
Arenicolous creatures live in the sand.
Troglofauna predominantly live in caves.
== Taxonomy ==
Terrestrial invasion is one of the most important events in the history of life. Terrestrial lineages evolved in several animal phyla, among which arthropods, vertebrates and mollusks are representatives of more successful groups of terrestrial animals.
Terrestrial animals do not form a unified clade; rather, they are a polyphyletic group that share only the fact that they live on land. The transition from an aquatic to terrestrial life by various groups of animals has occurred independently and successfully many times. Most terrestrial lineages originated under a mild or tropical climate during the Paleozoic and Mesozoic, whereas few animals became fully terrestrial during the Cenozoic.
If internal parasites are excluded, eleven phyla include free living species in terrestrial environments. These can be grouped as follows:
Three phyla contain species that have adapted totally to dry terrestrial environments, and which have no aquatic phase in their life cycles:
Arthropods — fully terrestrial members: hexapods (crown group being insects), arachnids, myriapods, and some land-evolved crustaceans such as woodlice, sandhoppers, coconut crab and terrestrial crabs; semi-terrestrial members include most species of crabs, crayfish, water fleas, copepods, and seed shrimp
Molluscs — mainly terrestrial gastropods: land snails and slugs; one species of coleoid cephalopod, the algae octopus, is also known to be routinely terrestrial
Chordates — specifically tetrapod vertebrates (especially amniotes); semiterrestrial members: non-caecilian amphibians (frogs and salamanders) and amphibious fish
Four phyla include species that depend on more or less moist habitats:
Annelids — mainly oligochaete clitellates such as earthworms, pot worms and some leeches, but require moist soil habitats, highly diverse and derived from their marine relatives
Onychophores (velvet worms) — the only solely terrestrial phylum, though require moist habitats and have restricted range
Platyhelminthes (flatworms) — specifically land planarians, require moist habitats and have restricted range
Nemerteans (ribbon worms) — specifically the 12 terrestrial species from the suborder Monostilifera, require moist habitats and have restricted range
Species in four more phyla, as well as some smaller species of arthropods and annelids, are microscopic animals that require a film of water to live in, and are therefore considered semi-terrestrial:
Gastrotrichs (hairy-backs) — live in transient terrestrial water and go dormant during desiccation
Rotifers (wheel animals) — live in transient terrestrial water and go dormant during desiccation
Nematodes (roundworms) — mostly parasitic but some (e.g. Caenorhabditis) are free-living detritivores, live in topsoil and go dormant during desiccation
Tardigrades (water bears) — live in transient terrestrial water and go dormant during desiccation
=== Difficulties ===
Labeling an animal species "terrestrial" or "aquatic" is often obscure and becomes a matter of judgment. Many animals considered terrestrial have a life-cycle that is partly dependent on being in water. Penguins, seals, and walruses sleep on land and feed in the ocean, yet they are all considered terrestrial. Many insects, e.g. mosquitos, and all terrestrial crabs, as well as other clades, have an aquatic life cycle stage: their eggs need to be laid in and to hatch in water; after hatching, there is an early aquatic form, either a nymph or larva.
There are crab species that are completely aquatic, crab species that are amphibious, and crab species that are terrestrial. Fiddler crabs are called "semi-terrestrial" since they make burrows in the muddy substrate, to which they retreat during high tides. When the tide is out, fiddler crabs search the beach for food. The same is true in the mollusca. Many hundreds of gastropod genera and species live in intermediate situations, such as for example, Truncatella. Some gastropods with gills live on land, and others with a lung live in the water.
As well as the purely terrestrial and the purely aquatic animals, there are many borderline species. There are no universally accepted criteria for deciding how to label these species, thus some assignments are disputed.
== Terrestrial panarthropods ==
Fossil evidence has shown that sea creatures, likely arthropods, first began to make forays onto land around 530 million years ago, in the Early Cambrian. There is little reason to believe, however, that animals first began living permanently on land around that time. A more likely hypothesis is that these early arthropods' motivation for venturing onto dry land was to mate (as modern horseshoe crabs do) or to lay eggs out of the reach of predators.
Three groups of arthropods had independently adapted to land by the end of the Cambrian: myriapods, hexapods and arachnids. By the late Ordovician, they may have fully terrestrialized. There are other groups of arthropods, all from malacostracan crustaceans, which independently became terrestrial at a later date: woodlice, sandhoppers, and terrestrial crabs. Additionally, the sister panarthropodan groups Onychophora (velvet worms) are also terrestrial, while the Eutardigrada are also adapted for land to some degree; both groups probably becoming so during the Early Devonian.
Among arthropods, many microscopic crustacean groups like copepods and amphipods and seed shrimp can go dormant when dry and live in transient bodies of water.
== Vertebrate terrestrialization ==
By approximately 375 million years ago the bony fish best adapted to life in shallow coastal/swampy waters (such as Tiktaalik roseae). Thanks to relatively strong, muscular limbs (which were likely weight-bearing, thus making them a preferable alternative to traditional fins in extremely shallow water), and lungs which existed in conjunction with gills, Tiktaalik and animals like it were able to establish a strong foothold on land by the end of the Devonian period. In the Carboniferous, tetrapods (losing their gills) became fully terrestrialized, allowing their expansion into most terrestrial niches, though later on some will return to being aquatic and conquer the air also.
== Terrestrial gastropods ==
Gastropod mollusks are one of the most successful animals that have diversified in the fully terrestrial habitat. They have evolved terrestrial taxa in more than nine lineages. They are commonly referred to as land snails and slugs.
Terrestrial invasion of gastropod mollusks has occurred in Neritopsina, Cyclophoroidea, Littorinoidea, Rissooidea, Ellobioidea, Onchidioidea, Veronicelloidea, Succineoidea, and Stylommatophora, and in particular, each of Neritopsina, Rissooidea and Ellobioidea has likely achieved land invasion more than once.
Most terrestrialization events have occurred during the Paleozoic or Mesozoic. Gastropods are especially unique due to several fully terrestrial and epifaunal lineages that evolved during the Cenozoic. Some members of rissooidean families Truncatellidae, Assimineidae, and Pomatiopsidae are considered to have colonized to land during the Cenozoic. Most truncatellid and assimineid snails amphibiously live in intertidal and supratidal zones from brackish water to pelagic areas. Terrestrial lineages likely evolved from such ancestors. The rissooidean gastropod family Pomatiopsidae is one of the few groups that have evolved fully terrestrial taxa during the late Cenozoic in the Japanese Archipelago only. Shifts from aquatic to terrestrial life occurred at least twice within two Japanese endemic lineages in Japanese Pomatiopsidae and it started in the Late Miocene.
About one-third of gastropod species are terrestrial. In terrestrial habitats they are subjected to daily and seasonal variation in temperature and water availability. Their success in colonizing different habitats is due to physiological, behavioral, and morphological adaptations to water availability, as well as ionic and thermal balance. They are adapted to most of the habitats on Earth. The shell of a snail is constructed of calcium carbonate, but even in acidic soils one can find various species of shell-less slugs. Land-snails, such as Xerocrassa seetzeni and Sphincterochila boissieri, also live in deserts, where they must contend with heat and aridity. Terrestrial gastropods are primarily herbivores and only a few groups are carnivorous. Carnivorous gastropods usually feed on other gastropod species or on weak individuals of the same species; some feed on insect larvae or earthworms.
== Semi-terrestrial animals ==
Semi-terrestrial animals are macroscopic animals that rely on very moist environments to thrive, they may be considered a transitional point between true terrestrial animals and aquatic animals. Among vertebrates, amphibians have this characteristic relying on a moist environment and breathing through their moist skin while reproducing in water.
Many other animal groups solely have terrestrial animals that live like this: land planarians, land ribbon worms, roundworms (nematodes), and land annelids (clitellates) who are very primitive and breathe through skin.
Clitellates or terrestrial annelids demonstrate many unique terrestrial adaptations especially in their methods of reproduction, they tend towards being simpler than their marine relatives, the bristleworms, lacking many of the complex appendages the latter have.
Velvet worms are prone to desiccation not due to breathing through their skin but due to their spiracles being inefficient at protecting from desiccation, like clitellates they demonstrate extensive terrestrial adaptations and differences from their marine relatives including live birth.
== Geoplankton ==
Many animals live in terrestrial environments by thriving in transient often microscopic bodies of water and moisture, these include rotifers and gastrotrichs which lay resilient eggs capable of surviving years in dry environments, and some of which can go dormant themselves. Nematodes are usually microscopic with this lifestyle. Although eutardigrades only have lifespans of a few months, they famously can enter suspended animation during dry or hostile conditions and survive for decades, which allows them to be ubiquitous in terrestrial environments despite needing water to grow and reproduce. Many microscopic crustacean groups like copepods and amphipods and seed shrimps are known to go dormant when dry and live in transient bodies of water too.
== See also ==
== Further reading ==
Clack J. A. (2002). Gaining ground: the origin and evolution of tetrapods. Indiana University Press, 369 pp., ISBN 978-0-253-34054-2.
Cloudsley-Thompson J. L. (1988). Evolution and adaptation of terrestrial arthropods. Springer, 141 pp., ISBN 978-3-540-18188-0.
Dejours P. et al. (1987). Comparative physiology: life in water and on land. Liviana Editrice, Italy, 556 pp., ISBN 978-0-387-96515-4.
Gordon M. S. & Olson E. C. (1995). Invasions of the land: the transitions of organisms from aquatic to terrestrial life. Columbia University Press, 312 pp., ISBN 978-0-231-06876-5.
Little C. (1983). The colonisation of land: Origins and adaptations of terrestrial animals. Cambridge University Press, Cambridge. 290 pp., ISBN 978-0-521-25218-8.
Little C. (1990). The terrestrial invasion. An ecophysiological approach to the origin of land animals. Cambridge University Press, Cambridge. 304 pp. ISBN 978-0-521-33669-7.
Zimmer, Carl (1999). At the Water's Edge : Fish with Fingers, Whales with Legs, and How Life Came Ashore but Then Went Back to Sea. New York: Touchstone. ISBN 0684856239.
== References ==
This article incorporates CC-BY-2.0 text from the reference and CC-BY-2.5 text from the reference and CC-BY-3.0 text from the reference | Wikipedia/Terrestrial_animal |
Whether invertebrates can feel pain is a contentious issue. Although there are numerous definitions of pain, almost all involve two key components. First, nociception is required. This is the ability to detect noxious stimuli which evokes a reflex response that moves the entire animal, or the affected part of its body, away from the source of the stimulus. The concept of nociception does not necessarily imply any adverse, subjective feeling; it is a reflex action. The second component is the experience of "pain" itself, or suffering—i.e., the internal, emotional interpretation of the nociceptive experience. Pain is therefore a private, emotional experience. Pain cannot be directly measured in other animals, including other humans; responses to putatively painful stimuli can be measured, but not the experience itself. To address this problem when assessing the capacity of other species to experience pain, argument-by-analogy is used. This is based on the principle that if a non-human animal's responses to stimuli are similar to those of humans, it is likely to have had an analogous experience. It has been argued that if a pin is stuck in a chimpanzee's finger and they rapidly withdraw their hand, then argument-by-analogy implies that like humans, they felt pain. It has been questioned why the inference does not then follow that a cockroach experiences pain when it writhes after being stuck with a pin. This argument-by-analogy approach to the concept of pain in invertebrates has been followed by others.
The ability to experience nociception has been subject to natural selection and offers the advantage of reducing further harm to the organism. While it might be expected therefore that nociception is widespread and robust, nociception varies across species. For example, the chemical capsaicin is commonly used as a noxious stimulus in experiments with mammals; however, the African naked mole-rat, Heterocephalus glaber, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P) in cutaneous sensory fibres, shows a unique and remarkable lack of pain-related behaviours to acid and capsaicin. Similarly, capsaicin triggers nociceptors in some invertebrates, but this substance is not noxious to Drosophila melanogaster (the common fruit fly).
Criteria that may indicate a potential for experiencing pain include:
Has a suitable nervous system and receptors
Physiological changes to noxious stimuli
Displays protective motor reactions that might include reduced use of an affected area such as limping, rubbing, holding or autotomy
Has opioid receptors and shows reduced responses to noxious stimuli when given analgesics and local anaesthetics
Shows trade-offs between stimulus avoidance and other motivational requirements
Shows avoidance learning
Exhibits high cognitive ability
== Suitable nervous system ==
=== Central nervous system ===
Brain size does not necessarily equate to complexity of function. Moreover, weight for body-weight, the cephalopod brain is in the same size bracket as the vertebrate brain, smaller than that of birds and mammals, but as big or bigger than most fish brains.
Invertebrate nervous systems are very unlike those of vertebrates and this dissimilarity has sometimes been used to reject the possibility of a pain experience in invertebrates. In humans, the neocortex of the brain has a central role in pain and it has been argued that any species lacking this structure will therefore be incapable of feeling pain. However, it is possible that different structures may be involved in the pain experience of other animals in the way that, for example, crustacean decapods have vision despite lacking a human visual cortex.
Two groups of invertebrates have notably complex brains: arthropods (insects, crustaceans, arachnids, and others) and modern cephalopods (octopuses, squid, cuttlefish) and other molluscs. The brains of arthropods and cephalopods arise from twin parallel nerve cords that extend through the body of the animal. Arthropods have a central brain with three divisions and large optic lobes behind each eye for visual processing. The brains of the modern cephalopods in particular are highly developed, comparable in complexity to the brains of some vertebrates (See also: Invertebrate brains). Emerging results suggest that a convergent evolutionary process has led to the selection of vertebrate-like neural organization and activity-dependent long-term synaptic plasticity in these invertebrates. Cephalopods stand out by having a central nervous system that shares prime electrophysiological and neuroanatomical features with vertebrates like no other invertebrate taxon.
=== Nociceptors ===
Nociceptors are sensory receptors that respond to potentially damaging stimuli by sending nerve signals to the brain. Although these neurons in invertebrates may have different pathways and relationships to the central nervous system than mammalian nociceptors, nociceptive neurons in invertebrates often fire in response to similar stimuli as mammals, such as high temperature (40 °C or more), low pH, capsaicin, and tissue damage. The first invertebrate in which a nociceptive cell was identified was the medicinal leech, Hirudo medicinalis, which has the characteristic segmented body of an Annelida, each segment possessing a ganglion containing the T (touch), P (pressure) and N (noxious) cells. Later studies on the responses of leech neurones to mechanical, chemical and thermal stimulation motivated researchers to write "These properties are typical of mammalian polymodal nociceptors".
There have been numerous studies of learning and memory using nociceptors in the sea hare, Aplysia. Many of these have focused on mechanosensory neurons innervating the siphon and having their somata (bulbous end) in the abdominal ganglion (LE cells). These LE cells display increasing discharge to increasing pressures, with maximal activation by crushing or tearing stimuli that cause tissue injury. Therefore, they satisfy accepted definitions of nociceptors. They also show similarities to vertebrate Aδ nociceptors, including a property apparently unique (among primary afferents) to nociceptors—sensitization by noxious stimulation. Either pinching or pinning the siphon decreased the threshold of the LE cells firing and enhanced soma excitability.
Nociceptors have been identified in a wide range of invertebrate species, including annelids, molluscs, nematodes and arthropods.
== Physiological changes ==
In vertebrates, potentially painful stimuli typically produce vegetative modifications such as tachycardia, pupil dilation, defecation, arteriole blood gases, fluid and electrolyte imbalance, and changes in blood flow, respiratory patterns, and endocrine excretions.
At the cellular level, injury or wounding of invertebrates leads to the directed migration and accumulation of haematocytes (defence cells) and neuronal plasticity, much the same as the responses of human patients undergoing surgery or after injury. In one study, heart rate in the crayfish, Procambarus clarkii, decreased following claw autotomy during an aggressive encounter.
Recording physiological changes in invertebrates in response to noxious stimuli will enhance the findings of behavioural observations and such studies should be encouraged. However, careful control is required because physiological changes can occur due to noxious, but non-pain related events, e.g. cardiac and respiratory activity in crustaceans is highly sensitive and responds to changes in water level, various chemicals and activity during aggressive encounters.
== Protective motor reactions ==
Invertebrates show a wide range of protective reactions to putatively painful stimuli. However, even unicellular animals will show protective responses to, for example, extremes of temperature. Many invertebrate protective reactions appear stereotyped and reflexive in action, perhaps indicating a nociceptive response rather than one of pain, but other responses are more plastic, especially when competing with other motivational systems (see section below), indicating a pain response analogous to that of vertebrates.
=== Mechanical stimulation ===
Rather than a simple withdrawal reflex, the flatworm, Notoplana aticola, displays a locomotory escape behaviour following pin pricks to the posterior end. Touching the larvae of fruit flies, Drosophila melanogaster, with a probe causes them to pause and move away from the stimulus; however, stronger mechanical stimulation evokes a more complex corkscrew-like rolling behaviour, i.e. the response is plastic. When a weak tactile stimulus is applied to the siphon of the sea-hare Aplysia californica, the animal rapidly withdraws the siphon between the parapodia. It is sometimes claimed this response is an involuntary reflex (e.g. see Aplysia gill and siphon withdrawal reflex); however, the complex learning associated with this response (see 'Learned Avoidance' below) suggests this view might be overly simplistic.
In 2001, Walters and colleagues published a report that described the escape responses of the tobacco hornworm caterpillar (Manduca sexta) to mechanical stimulation. These responses, particularly their plasticity, were remarkably similar to vertebrate escape responses.
=== Autotomy ===
Over 200 species of invertebrates are capable of using autotomy (self amputation) as an avoidance or protective behaviour including:
land slugs (Prophysaon)
sea snails (Oxynoe panamensis)
crickets
spiders
crabs
lobsters
octopuses
These animals can voluntarily shed appendages when necessary for survival. Autotomy can occur in response to chemical, thermal and electrical stimulation, but is perhaps most frequently a response to mechanical stimulation during capture by a predator. Autotomy serves either to improve the chances of escape or to reduce further damage occurring to the remainder of the animal such as the spread of a chemical toxin after being stung, but the 'decision' to shed a limb or part of a body and the considerable costs incurred by this suggests a pain response rather than simply a nociceptive reflex.
=== Thermal stimulation ===
A heated probe (»42 °C or 108 °F) evokes a complex, corkscrew-like rolling avoidance behaviour in Drosophila larvae which occurs in as little as 0.4 seconds; a non-heated probe does not cause this avoidance behaviour. In contrast, cold stimuli (≤14 °C or 57.2 °F) primarily elicit a bilateral full-body contraction along the head-to-tail axis; larvae might also respond by lifting their head and/or tail, but these responses occur less frequently with decreasing temperatures. Land snails show an avoidance response to being placed on a hotplate (»40 °C or 104 °F) by lifting the anterior portion of the extended foot. A 2015 study found that crayfish (Procambarus clarkii) respond adversely to high temperatures, but not to low temperatures.
=== Chemical stimulation ===
Crustaceans are known to respond to acids in ways that indicate nociception and/or pain. The prawn Palaemon elegans shows protective motor reactions when their antennae are treated with the irritants acetic acid or sodium hydroxide. The prawns specifically groom the treated antennae and rub them against the tank, showing they are aware of the location of the noxious stimulus on their body rather than exhibiting a generalised response to stimulation. In Carcinus maenas, the common shore crab, acetic acid induces a number of behavioral changes, including movement of the mouthparts, rubbing with the claws, and increased attempts to escape from an enclosure.
Under natural conditions, orb-weaving spiders (Argiope spp.) undergo autotomy (self-amputation) if they are stung in a leg by wasps or bees. Under experimental conditions, when spiders were injected in the leg with bee or wasp venom, they shed this appendage. But if they are injected with only saline, they rarely autotomize the leg, indicating it is not the physical insult or the ingress of fluid per se that causes autotomy. Spiders injected with venom components which cause injected humans to report pain (serotonin, histamine, phospholipase A2 and melittin) autotomize the leg, but if the injections contain venom components which do not cause pain to humans, autotomy does not occur.
Drosophila melanogaster larvae respond to acids and menthol with a stereotyped nociceptive rolling response, identical to the behavior seen in response to high-temperature and mechanical insult. The electrophilic chemical allyl isothiocyanate causes nociceptive sensitization in larvae. Adult flies find menthol, AITC, capsaicin, and a number of other chemicals to be aversive, affecting both the proboscis extension reflex and egg-lay site preference.
Acids are also known to activate nociceptors in the nematode Caenorhabditis elegans and in Hirudo medicinalis, commonly known as the medicinal leech.
=== Electrical stimulation ===
The sea-slug, Tritonia diomedia, possesses a group of sensory cells, "S-cells", situated in the pleural ganglia, which initiate escape swimming if stimulated by electric shock. Similarly, the mantis shrimp Squilla mantis shows avoidance of electric shocks with a strong tail-flick escape response. Both these responses appear to be rather fixed and reflexive, however, other studies indicate a range of invertebrates exhibit considerably more plastic responses to electric shocks.
Because of their soft bodies, hermit crabs rely on shells for their survival, but, when they are given small electric shocks within their shells, they evacuate these. The response, however, is influenced by the attractiveness of the shell; more preferred shells are only evacuated when the crabs are given a higher voltage shock, indicating this is not a simple reflex behaviour.
In studies on learning and the Aplysia gill and siphon withdrawal reflex, Aplysia received an electric shock on the siphon each time their gill relaxed below a criterion level. Aplysia learned to keep their gills contracted above the criterion level—an unlikely outcome if the response was due to a nociceptive experience.
Drosophila feature widely in studies of invertebrate nociception and pain. It has been known since 1974 that these fruit-flies can be trained with sequential presentations of an odour and electric shock (odour–shock training) and will subsequently avoid the odour because it predicts something "bad". A similar response has been found in the larvae of this species. In an intriguing study, Drosophila learned two kinds of prediction regarding a 'traumatic' experience. If an odour preceded an electric shock during training, it predicted shock and the flies subsequently avoided it. When the sequence of events during training was reversed, i.e. odour followed shock, the odour predicted relief from shock and flies approached it. The authors termed this latter effect "relief" learning.
Many invertebrate species learn to withdraw from, or alter their behaviour in response to, a conditioned stimulus when this has been previously paired with an electric shock—cited by Sherwin—and include snails, leeches, locusts, bees and various marine molluscs.
If vertebrate species are used in studies on protective or motor behaviour and they respond in similar ways to those described above, it is usually assumed that the learning process is based on the animal experiencing a sensation of pain or discomfort from the stimulus, e.g. an electric shock. Argument-by-analogy suggests an analogous experience occurs in invertebrates.
== Opioid receptors, effects of local anaesthetics or analgesics ==
In vertebrates, opiates modulate nociception and opioid receptor antagonists, e.g. naloxone and CTOP, reverse this effect. So, if opiates have similar effects in invertebrates as vertebrates, they should delay or reduce any protective response and the opioid antagonist should counteract this. It has been found that molluscs and insects have opioid binding sites or opioid general sensitivity. Certainly there are many examples of neuropeptides involved in vertebrate pain responses being found in invertebrates; for example, endorphins have been found in platyhelminthes, molluscs, annelids, crustaceans and insects. Apart from analgesia, there are other effects of exogenous opiates specifically being involved in feeding behaviour and activation of immunocytes. These latter functions might explain the presence of opioids and opioid receptors in extremely simple invertebrates and unicellular animals.
=== Nematodes ===
Nematodes avoid extremes of temperature. Morphine increases the latency of this defensive response in the parasitic Ascaris suum. In a study on the effects of opiates in Caenorhabditis elegans, 76% of a non-treated group exhibited a rapid, reflexive withdrawal to heat, whereas 47%, 36% and 39% of morphine, endomorphin 1 and endomorphin 2 treated worms (respectively) withdrew. These effects were reversed with the opioid receptor antagonists naloxone and CTOP, leading the authors to conclude that thermonocifensive behaviour in C. elegans was modulated by opioids.
=== Molluscs ===
Slugs and snails have an opioid receptor system. In experiments on different terrestrial snails, morphine prolonged the latency of the snails' raising their foot in response to being placed on a hot (40 °C) surface. The analgesic effects of the morphine were eliminated by naloxone as is seen in humans and other vertebrates. There was also habituation to morphine. Snails administered with morphine for four days did not differ from the control ones in tests on pain sensitivity and analgesia was achieved only at a higher dose.
=== Crustaceans ===
Evidence of the capacity for invertebrates to experience nociception and pain has been widely studied in crustaceans. In the crab Neohelice granulata, electric shocks delivered via small holes in the carapace elicited a defensive threat display. Injection of morphine reduced the crabs' sensitivity to the shock in a dose-dependent manner, with the effect declining with increasing duration between morphine injection and shock. Naloxone injection inhibited the effects of morphine, as is seen in vertebrates. Morphine also had inhibitory effects on the escape tail-flick response to electric shock in the mantis shrimp, Squilla mantis, that was reversed by naloxone, indicating that the effect is found in crustacean groups other than decapods. When the irritants acetic acid or sodium hydroxide were applied to the antennae of grass prawns, Penaeus monodon, there was an increase in rubbing and grooming of the treated areas which was not seen if they had previously been treated with a local anaesthetic, benzocaine, however, the benzocaine did not eliminate the level of rubbing seen in response to mechanical stimulation with forceps. There was no effect of benzocaine on the general locomotion of the prawns, so the reduction in rubbing and grooming was not simply due to inactivity of the animal. Another local anaesthetic, xylocaine, reduced the stress of eyestalk ablation in female whiteleg shrimps, Litopenaeus vannamei, as indicated by levels of feeding and swimming.
It has not always been possible to replicate these findings in crustaceans. In one study, three decapod crustacean species, Louisiana red swamp crayfish, white shrimp and grass shrimp, were tested for nociceptive behaviour by applying sodium hydroxide, hydrochloric acid, or benzocaine to the antennae. This caused no change in behaviour in these three species compared to controls. Animals did not groom the treated antenna, and there was no difference in movement of treated individuals and controls. Extracellular recordings of antennal nerves in the Louisiana red swamp crayfish revealed continual spontaneous activity, but no neurons that were reliably excited by the application of sodium hydroxide or hydrochloric acid. The authors concluded there was no behavioural or physiological evidence that the antennae contained specialized nociceptors that responded to pH. It could be argued that differences in the findings between studies may be due to responses to extreme pH being inconsistently evoked across species.
It has been argued that the analgesic effects of morphine should not be used as a criterion of the ability of animals, at least crustaceans, to experience pain. In one study, shore crabs, Carcinus maenas received electric shocks in a preferred dark shelter but not if they remained in an unpreferred light area. Analgesia from morphine should have enhanced movement to the preferred dark area because the crabs would not have experienced 'pain' from the electric shock. However, morphine inhibited rather than enhanced this movement, even when no shock was given. Morphine produced a general effect of non-responsiveness rather than a specific analgesic effect, which could also explain previous studies claiming analgesia. However, the researchers argued that other systems such as the enkephalin or steroid systems might be used in pain modulation by crustaceans and that behavioural responses should be considered rather than specific physiological and morphological features.
=== Insects ===
Morphine extends the period that crickets remain on the heated surface of a hotplate. One study has found that fruit flies can experience chronic pain. Some insects have been observed grooming their injuries.
A 2022 review found strong evidence for pain in adult insects of two orders (Blattodea: cockroaches and termites; Diptera: flies and mosquitoes) and found substantial evidence for pain in adult insects of three additional orders (Hymenoptera: sawflies, wasps, bees, and ants; Lepidoptera: moths and butterflies; and Orthoptera: grasshoppers, crickets, wētā and locusts), in addition to some juvenile insects. The authors identified significant evidence gaps particularly around juvenile insects and called attention to a need for more research to be undertaken on insect pain. Based on these findings, the authors also considered the welfare implications of human activities such as insect farming and pest control.
== Trade-offs between stimulus avoidance and other motivational requirements ==
This is a particularly important criterion for assessing whether an animal has the capacity to experience pain rather than only nociception. Nociceptive responses do not require consciousness or higher neural processing; this results in relatively fixed, reflexive actions. However, the experience of pain does involve higher neural centres which also take into account other factors of relevance to the animal, i.e. competing motivations. This means that a response to the experience of pain is likely to be more plastic than a nociceptive response when there are competing factors for the animal to consider.
Robert Elwood and Mirjam Appel at the Queen's University of Belfast argue that pain may be inferred when the responses to a noxious stimulus are not reflexive but are traded off against other motivational requirements, the experience is remembered and the situation is avoided in the future. They investigated this by giving hermit crabs small electric shocks within their shells. Only crabs given shocks evacuated their shells indicating the aversive nature of the stimulus, but fewer crabs evacuated from a preferred species of shell demonstrating a motivational trade-off. Most crabs, however, did not evacuate at the shock level used, but when these shocked crabs were subsequently offered a new shell, they were more likely to approach and enter the new shell. They approached the new shell more quickly, investigated it for a shorter time and used fewer cheliped probes within the aperture prior to moving in. This demonstrates the experience of the electric shock altered future behaviour in a manner consistent with a marked shift in motivation to get a new shell to replace the one previously occupied.
== Learned avoidance ==
Learning to avoid a noxious stimulus indicates that prior experience of the stimulus is remembered by the animal and appropriate action taken in the future to avoid or reduce potential damage. This type of response is therefore not the fixed, reflexive action of nociceptive avoidance.
=== Habituation and sensitization ===
Habituation and sensitisation are two simple, but widespread, forms of learning. Habituation refers to a type of non-associative learning in which repeated exposure to a stimulus leads to decreased response. Sensitization is another form of learning in which the progressive amplification of a response follows repeated administrations of a stimulus.
When a tactile stimulus is applied to the skin of Aplysia californica, the animal withdraws the siphon and gill between the parapodia. This defensive withdrawal, known as the Aplysia gill and siphon withdrawal reflex, has been the subject of much study on learning behaviour. Generally, these studies have involved only weak, tactile stimulation and are therefore more relevant to the question of whether invertebrates can experience nociception, however, some studies have used electric shocks to examine this response (See sections on "Electrical stimulation" and "Operant conditioning").
=== Location avoidance ===
Avoidance learning was examined in the crab Neohelice granulata by placing the animals in a dark compartment of a double-chamber device and allowing them to move towards a light compartment. Experimental crabs received a shock in the light compartment, whilst controls did not. After 1 min, both experimental and control crabs were free to return to the dark compartment. The learned outcome was not a faster escape response to the stimulus but rather refraining from re-entering the light compartment. A single trial was enough to establish an association between light and shock that was detected up to 3 hours later.
Studies on crayfish, Procambarus clarkia, demonstrated that they learned to associate the turning on of a light with a shock that was given 10 seconds later. They learned to respond by walking to a safe area in which the shock was not delivered. However, this only occurred if the crayfish were facing the area to which they could retreat to avoid the shock. If they were facing away from the safe area the animal did not walk but responded to the shock by a tail-flick escape response. Despite repeated pairings of light and shock the animals did not learn to avoid the shock by tail-flicking in response to light. Curiously, when the animals that had experienced shocks whilst facing away from the safe area were subsequently tested facing towards the safe area they showed a very rapid avoidance of the shock upon the onset of the light. Thus, they seemed to have learned the association although they had not previously used it to avoid the shock - much like mammalian latent learning. These studies show an ability in decapods that fulfils several criteria for pain experience rather than nociception.
=== Conditioned suppression ===
Honeybees extend their proboscis when learning about novel odours. In one study on this response, bees learnt to discriminate between two odours, but then learned to suppress the proboscis extension response when one of the odours was paired with an electric shock. This indicates the sensation was aversive to the bee, however, the response was plastic rather than simply reflexive, indicating pain rather than nociception.
=== Operant conditioning ===
Operant studies using vertebrates have been conducted for many years. In such studies, an animal operates or changes some part of the environment to gain a positive reinforcement or avoid a punishment one. In this way, animals learn from the consequence of their own actions, i.e. they use an internal predictor. Operant responses indicate a voluntary act; the animal exerts control over the frequency or intensity of its responses, making these distinct from reflexes and complex fixed action patterns. A number of studies have revealed surprising similarities between vertebrates and invertebrates in their capacity to use operant responses to gain positive reinforcements, but also to avoid positive punishment that in vertebrates would be described as 'pain'.
==== Snail ====
It has been shown that snails will operate a manipulandum to electrically self-stimulate areas of their brain. Balaban and Maksimova surgically implanted fine wire electrodes in two regions of the brains of snails (Helix sp.). To receive electrical stimulation of the brain, the snail was required to displace the end of a rod. When pressing the rod delivered self-stimulation to the mesocerebrum (which is involved in sexual activity) the snails increased the frequency of operating the manipulandum compared to the baseline spontaneous frequency of operation. However, when stimulation was delivered to the parietal ganglion, the snails decreased the frequency of touching the rod compared to the baseline spontaneous frequency. These increases and decreases in pressing are positive reinforcement and punishment responses typical of those seen with vertebrates.
==== Aplysia ====
To examine the gill and siphon withdrawal response to a putatively painful stimulus, Aplysia were tested in pairs. During the initial training period, the experimental animal received a siphon shock each time its gill relaxed below a criterion level, and the yoked control animal received a shock whenever the experimental animal did, regardless of its own gill position. The experimental animals spent more time with their gills contracted above the criterion level than did the control animals during each period, demonstrating operant conditioning.
==== Drosophila ====
A fly-controlled heat-box has been designed to study operant conditioning in several studies of Drosophila. Each time a fly walks into the designated half of the tiny dark chamber, the whole space is heated. As soon as the animal leaves the punished half, the chamber temperature reverts to normal. After a few minutes, the animals restrict their movements to one-half of the chamber, even if the heat is switched off.
A Drosophila flight simulator has been used to examine operant conditioning. The flies are tethered in an apparatus that measures the yaw torque of their flight attempts and stabilizes movements of the panorama. The apparatus controls the fly's orientation based on these attempts. When the apparatus was set up to direct a heat beam on the fly if it "flew" to certain areas of its panorama, the flies learned to prefer and avoid certain flight orientations in relation to the surrounding panorama. The flies "avoided" areas that caused them to receive heat.
These experiments show that Drosophila can use operant behaviour and learn to avoid noxious stimuli. However, these responses were plastic, complex behaviours rather than simple reflex actions, consistent more with the experience of pain rather than simply nociception.
== Cognitive abilities ==
It could be argued that a high cognitive ability is not necessary for the experience of pain; otherwise, it could be argued that humans with less cognitive capacity have a lower likelihood of experiencing pain. However, most definitions of pain indicate some degree of cognitive ability. Several of the learned and operant behaviours described above indicate that invertebrates have high cognitive abilities. Other examples include:
Social transmission of information during the waggle dance of honeybees.
Idiothetic orientation by spiders, i.e. they memorize information about their previous movements.
Detour behaviour in which spiders choose to take an indirect route to a goal rather than the most direct route, thereby indicating flexibility in behaviour and route planning, and possibly insight learning.
Conceptualisation in the honeybee, Apis mellifera.
Problem solving in leafcutter ants, Atta colombica.
Numeracy in the yellow mealworm beetle, Tenebrio molitor, and honeybee.
=== Non-stereotyped behavior ===
Charles Darwin was interested in worms and "how far they acted consciously, and how much mental power they displayed." In The Formation of Vegetable Mould through the Action of Worms, Darwin described complex behaviors by worms when plugging their burrows. He suggested that worms appear to "have the power of acquiring some notion, however crude, of the shape of an object and of their burrows" and if so, "they deserve to be called intelligent; for they then act in nearly the same manner as would a man under similar circumstances."
Donald Griffin's 1984 Animal Thinking defends the idea that invertebrate behavior is complex, intelligent, and somewhat general. He points to examples in W. S. Bristowe's 1976 The World of Spiders detailing how spiders respond adaptively to novel conditions. For instance, a spider can eat a fly held in front of it by an experimenter, bypassing the usual step of moving toward an insect caught on its web. A spider may adapt the shape of its web to abnormal circumstances, suggesting that the web is not just built with a fixed template. Griffin also considers leaf-cutter ants, with central nervous systems "less than a millimeter in diameter", and asks: "Can the genetic instructions stored in such a diminutive central nervous system prescribe all of the detailed motor actions carried out by one of these ants? Or is it more plausible to suppose that their DNA programs the development of simple generalizations [...]?"
In other instances invertebrates display more "dumb", pre-programmed behavior. Darwin himself cites examples involving ants, sphexes, and bees. Dean Wooldridge described how a sphex wasp brings a paralyzed cricket to its burrow and then goes inside to inspect the burrow before coming back out and bringing the cricket in. If the cricket is moved slightly while the wasp is away making its first inspection, the wasp upon returning from the burrow reorients the cricket to its proper position and then proceeds to check the burrow again, even though it was already checked just before. If the cricket is moved again, the routine repeats once more. This process has been repeated up to 40 times in a row. Based on this example, Douglas Hofstadter coined the term "sphexish" to mean deterministic or pre-programmed.
=== Social interaction ===
Social behavior is widespread in invertebrates, including cockroaches, termites, aphids, thrips, ants, bees, Passalidae, Acari, spiders, and more. Social interaction is particularly salient in eusocial species but applies to other invertebrates as well.
Jeffrey A. Lockwood, citing previous authors, argues that awareness of how other minds operate may be an important requirement for social interaction. Social behavior indicates that insects can recognize information conveyed by other insects, and this suggests they may also have some self-awareness. Lockwood asserts: "it is rather implausible to contend that through sensory mechanisms an insect is aware of the environment, other insects, and the needs of conspecifics but through some neural blockage, the same insect is selectively unconscious of sensory input about itself."
== Protective legislation ==
In the UK from 1993 to 2012, the common octopus (Octopus vulgaris) was the only invertebrate protected under the Animals (Scientific Procedures) Act 1986. In 2012, this legislation was extended to include all cephalopods, in accordance with a general EU directive, which states that "there is scientific evidence of their [cephalopods] ability to experience pain, suffering, distress and lasting harm."
== Public perception ==
A 2021 representative poll of 4,446 Americans found that 65 percent of people in the US believe that honeybees can feel pain, while 56 percent believe that ants can feel pain.
A similar poll conducted in the UK (n=1963) likewise found that "the vast majority of participants agreed that lobsters (83.03 %), octopuses (80.65 %), and crabs (78.09 %) can feel pain", and a majority also thought that "honey bees (73.09 %), shrimp (62.20 %), caterpillars (58.06 %), and flies (54.23 %) could feel pain."
== See also ==
== Notes ==
== References ==
== Further references ==
Crook, RJ; Walters, ET (2011). "Nociceptive Behavior and Physiology of Molluscs: Animal Welfare Implications". ILAR Journal. 52 (2): 185–195. doi:10.1093/ilar.52.2.185. PMID 21709311.
Crook, RJ (2013). "The welfare of invertebrate animals in research: Can science's next generation improve their lot?" (PDF). Journal of Postdoctoral Research. 1 (2): 1–20.
Horvath, K; Angeletti, D; Nascetti, G; Carere, C (2013). "Invertebrate welfare: an overlooked issue". Annali dell'Istituto Superiore di Sanità. 49 (1): 9–17. doi:10.4415/ANN_13_01_04. PMID 23535125. Archived from the original on 2016-06-01. Retrieved 2014-01-21. | Wikipedia/Pain_in_invertebrates |
Marine invertebrates are invertebrate animals that live in marine habitats, and make up most of the macroscopic life in the oceans. It is a polyphyletic blanket term that contains all marine animals except the marine vertebrates, including the non-vertebrate members of the phylum Chordata such as lancelets, sea squirts and salps. As the name suggests, marine invertebrates lack any mineralized axial endoskeleton, i.e. the vertebral column, and some have evolved a rigid shell, test or exoskeleton for protection and/or locomotion, while others rely on internal fluid pressure to support their bodies. Marine invertebrates have a large variety of body plans, and have been categorized into over 30 phyla.
== Evolution ==
The earliest animals were marine invertebrates, that is, vertebrates came later. Animals are multicellular eukaryotes, and are distinguished from plants, algae, and fungi by lacking cell walls. Marine invertebrates are animals that inhabit a marine environment apart from the vertebrate members of the chordate phylum; invertebrates lack a vertebral column. Some have evolved a shell or a hard exoskeleton.
The earliest animals may belong to the genus Dickinsonia, 571 million to 539 million years ago. Individual Dickinsonia typically resemble a bilaterally symmetrical ribbed oval. They kept growing until they were covered with sediment or otherwise killed, and spent most of their lives with their bodies firmly anchored to the sediment. Their taxonomic affinities are presently unknown, but their mode of growth is consistent with a bilaterian affinity.
Apart from Dickinsonia, the earliest widely accepted animal fossils are the rather modern-looking cnidarians (the group that includes jellyfish, sea anemones and Hydra), possibly from around 580 Ma The Ediacara biota, which flourished for the last 40 million years before the start of the Cambrian, were the first animals more than a very few centimetres long. Like Dickinsonia, many were flat with a "quilted" appearance, and seemed so strange that there was a proposal to classify them as a separate kingdom, Vendozoa. Others, however, have been interpreted as early molluscs (Kimberella), echinoderms (Arkarua), and arthropods (Spriggina, Parvancorina). There is still debate about the classification of these specimens, mainly because the diagnostic features which allow taxonomists to classify more recent organisms, such as similarities to living organisms, are generally absent in the Ediacarans. However, there seems little doubt that Kimberella was at least a triploblastic bilaterian animal, in other words, an animal significantly more complex than the cnidarians.
The small shelly fauna are a very mixed collection of fossils found between the Late Ediacaran and Middle Cambrian periods. The earliest, Cloudina, shows signs of successful defense against predation and may indicate the start of an evolutionary arms race. Some tiny Early Cambrian shells almost certainly belonged to molluscs, while the owners of some "armor plates," Halkieria and Microdictyon, were eventually identified when more complete specimens were found in Cambrian lagerstätten that preserved soft-bodied animals.
In the 1970s, there was already a debate about whether the emergence of the modern phyla was "explosive" or gradual but hidden by the shortage of Precambrian animal fossils. A re-analysis of fossils from the Burgess Shale lagerstätte increased interest in the issue when it revealed animals, such as Opabinia, which did not fit into any known phylum. At the time these were interpreted as evidence that the modern phyla had evolved very rapidly in the Cambrian explosion and that the Burgess Shale's "weird wonders" showed that the Early Cambrian was a uniquely experimental period of animal evolution. Later discoveries of similar animals and the development of new theoretical approaches led to the conclusion that many of the "weird wonders" were evolutionary "aunts" or "cousins" of modern groups—for example that Opabinia was a member of the lobopods, a group which includes the ancestors of the arthropods, and that it may have been closely related to the modern tardigrades. Nevertheless, there is still much debate about whether the Cambrian explosion was really explosive and, if so, how and why it happened and why it appears unique in the history of animals.
== Classification ==
Invertebrates are grouped into different phyla. Informally phyla can be thought of as a way of grouping organisms according to their body plan.: 33 A body plan refers to a blueprint which describes the shape or morphology of an organism, such as its symmetry, segmentation and the disposition of its appendages. The idea of body plans originated with vertebrates, which were grouped into one phylum. But the vertebrate body plan is only one of many, and invertebrates consist of many phyla or body plans. The history of the discovery of body plans can be seen as a movement from a worldview centred on vertebrates, to seeing the vertebrates as one body plan among many. Among the pioneering zoologists, Linnaeus identified two body plans outside the vertebrates; Cuvier identified three; and Haeckel had four, as well as the Protista with eight more, for a total of twelve. For comparison, the number of phyla recognised by modern zoologists has risen to 35.
Historically body plans were thought of as having evolved in rapidly during the Cambrian explosion, but a more nuanced understanding of animal evolution suggests a gradual development of body plans throughout the early Palaeozoic and beyond. More generally a phylum can be defined in two ways: as described above, as a group of organisms with a certain degree of morphological or developmental similarity (the phenetic definition), or a group of organisms with a certain degree of evolutionary relatedness (the phylogenetic definition).
As on land and in the air, invertebrates make up a great majority of all macroscopic life, as the vertebrates makes up a subphylum of one of over 30 known animal phyla, making the term almost meaningless for taxonomic purpose. Invertebrate sea life includes the following groups, some of which are phyla:
Acoela, among the most primitive bilateral animals;
Annelida, (polychaetes and sea leeches);
Brachiopoda, marine animals that have hard "valves" (shells) on the upper and lower surfaces ;
Bryozoa, also known as moss animals or sea mats;
Chaetognatha, commonly known as arrow worms, are a phylum of predatory marine worms that are a major component of plankton;
Cephalochordata represented in the modern oceans by the lancelets (also known as Amphioxus);
Cnidaria, such as jellyfish, sea anemones, and corals;
Crustacea, including lobsters, crabs, shrimp, crayfish, barnacles, hermit crabs, mantis shrimps, and copepods;
Ctenophora, also known as comb jellies, the largest animals that swim by means of cilia;
Echinodermata, including sea stars, brittle stars, sea urchins, sand dollars, sea cucumbers, crinoids, and sea daisies;
Echiura, also known as spoon worms;
Gnathostomulids, slender to thread-like worms, with a transparent body that inhabit sand and mud beneath shallow coastal waters;
Gastrotricha, often called hairy backs, found mostly interstitially in between sediment particles;
Hemichordata, includes acorn worms, solitary worm-shaped organisms;
Kamptozoa, goblet-shaped sessile aquatic animals, with relatively long stalks and a "crown" of solid tentacles, also called Entoprocta;
Kinorhyncha, segmented, limbless animals, widespread in mud or sand at all depths, also called mud dragons;
Loricifera, very small to microscopic marine sediment-dwelling animals only discovered in 1983;
Mollusca, including shellfish, squid, octopus, whelks, Nautilus, cuttlefish, nudibranchs, scallops, sea snails, Aplacophora, Caudofoveata, Monoplacophora, Polyplacophora, and Scaphopoda;
Myzostomida, a taxonomic group of small marine worms which are parasitic on crinoids or "sea lilies";
Nemertinea, also known as "ribbon worms" or "proboscis worms";
Orthonectida, a small phylum of poorly known parasites of marine invertebrates that are among the simplest of multi-cellular organisms;
Phoronida, a phylum of marine animals that filter-feed with a lophophore (a "crown" of tentacles), and build upright tubes of chitin to support and protect their soft bodies;
Placozoa, small, flattened, multicellular animals around 1 millimetre across and the simplest in structure. They have no regular outline, although the lower surface is somewhat concave, and the upper surface is always flattened;
Porifera (sponges), multicellular organisms that have bodies full of pores and channels allowing water to circulate through them;
Priapulida, or penis worms, are a phylum of marine worms that live marine mud. They are named for their extensible spiny proboscis, which, in some species, may have a shape like that of a human penis;
Pycnogonida, also called sea spiders, are unrelated to spiders, or even to arachnids which they resemble;
Sipunculida, also called peanut worms, is a group containing 144–320 species (estimates vary) of bilaterally symmetrical, unsegmented marine worms;
Tunicata, also known as sea squirts or sea pork, are filter feeders attached to rocks or similarly suitable surfaces on the ocean floor;
Some flatworms of the classes Turbellaria and Monogenea;
Xenoturbella, a genus of bilaterian animals that contains only two marine worm-like species;
Xiphosura, includes a large number of extinct lineages and only four recent species in the family Limulidae, which include the horseshoe crabs.
Arthropods total about 1,113,000 described extant species, molluscs about 85,000 and chordates about 52,000.
== Marine sponges ==
Sponges are animals of the phylum Porifera (Modern Latin for bearing pores). They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through them, consisting of jelly-like mesohyl sandwiched between two thin layers of cells. They have unspecialized cells that can transform into other types and that often migrate between the main cell layers and the mesohyl in the process. Sponges do not have nervous, digestive or circulatory systems. Instead, most rely on maintaining a constant water flow through their bodies to obtain food and oxygen and to remove wastes.
Sponges are similar to other animals in that they are multicellular, heterotrophic, lack cell walls and produce sperm cells. Unlike other animals, they lack true tissues and organs, and have no body symmetry. The shapes of their bodies are adapted for maximal efficiency of water flow through the central cavity, where it deposits nutrients, and leaves through a hole called the osculum. Many sponges have internal skeletons of spongin and/or spicules of calcium carbonate or silicon dioxide. All sponges are sessile aquatic animals. Although there are freshwater species, the great majority are marine (salt water) species, ranging from tidal zones to depths exceeding 8,800 m (5.5 mi).
While most of the approximately 5,000–10,000 known species feed on bacteria and other food particles in the water, some host photosynthesizing micro-organisms as endosymbionts and these alliances often produce more food and oxygen than they consume. A few species of sponge that live in food-poor environments have become carnivores that prey mainly on small crustaceans.
Linnaeus mistakenly identified sponges as plants in the order Algae. For a long time thereafter sponges were assigned to a separate subkingdom, Parazoa (meaning beside the animals). They are now classified as a paraphyletic phylum from which the higher animals have evolved.
== Marine cnidarians ==
Cnidarians (Greek for nettle) are distinguished by the presence of stinging cells, specialized cells that they use mainly for capturing prey. Cnidarians include corals, sea anemones, jellyfish and hydrozoans. They form a phylum containing over 10,000 species of animals found exclusively in aquatic (mainly marine) environments. Their bodies consist of mesoglea, a non-living jelly-like substance, sandwiched between two layers of epithelium that are mostly one cell thick. They have two basic body forms: swimming medusae and sessile polyps, both of which are radially symmetrical with mouths surrounded by tentacles that bear cnidocytes. Both forms have a single orifice and body cavity that are used for digestion and respiration.
Fossil cnidarians have been found in rocks formed about 580 million years ago. Fossils of cnidarians that do not build mineralized structures are rare. Scientists currently think cnidarians, ctenophores and bilaterians are more closely related to calcareous sponges than these are to other sponges, and that anthozoans are the evolutionary "aunts" or "sisters" of other cnidarians, and the most closely related to bilaterians.
Cnidarians are the simplest animals in which the cells are organised into tissues. The starlet sea anemone is used as a model organism in research. It is easy to care for in the laboratory and a protocol has been developed which can yield large numbers of embryos on a daily basis. There is a remarkable degree of similarity in the gene sequence conservation and complexity between the sea anemone and vertebrates. In particular, genes concerned in the formation of the head in vertebrates are also present in the anemone.
== Marine worms ==
Worms (Old English for serpent) typically have long cylindrical tube-like bodies and no limbs. Marine worms vary in size from microscopic to over 1 metre (3.3 ft) in length for some marine polychaete worms (bristle worms) and up to 58 metres (190 ft) for the marine nemertean worm (bootlace worm). Some marine worms occupy a small variety of parasitic niches, living inside the bodies of other animals, while others live more freely in the marine environment or by burrowing underground.
Different groups of marine worms are related only distantly, so they are found in several different phyla such as the Annelida (segmented worms), Chaetognatha (arrow worms), Hemichordata, and Phoronida (horseshoe worms). Many of these worms have specialized tentacles used for exchanging oxygen and carbon dioxide and also may be used for reproduction. Some marine worms are tube worms, such as the giant tube worm which lives in waters near underwater volcanoes and can withstand temperatures up to 90 degrees Celsius.
Platyhelminthes (flatworms) form another worm phylum which includes a class Cestoda of parasitic tapeworms. The marine tapeworm Polygonoporus giganticus, found in the gut of sperm whales, can grow to over 30 m (100 ft).
Nematodes (roundworms) constitute a further worm phylum with tubular digestive systems and an opening at both ends. Over 25,000 nematode species have been described, of which more than half are parasitic. It has been estimated another million remain undescribed. They are ubiquitous in marine, freshwater and terrestrial environments, where they often outnumber other animals in both individual and species counts. They are found in every part of the Earth's lithosphere, from the top of mountains to the bottom of oceanic trenches. By count they represent 90% of all animals on the ocean floor. Their numerical dominance, often exceeding a million individuals per square meter and accounting for about 80% of all individual animals on earth, their diversity of life cycles, and their presence at various trophic levels point at an important role in many ecosystems.
== Echinoderms ==
Echinoderms (Greek for spiny skin) is a phylum which contains only marine invertebrates. The adults are recognizable by their radial symmetry (usually five-point) and include starfish, sea urchins, sand dollars, and sea cucumbers, as well as the sea lilies. Echinoderms are found at every ocean depth, from the intertidal zone to the abyssal zone. The phylum contains about 7,000 living species, making it the second-largest grouping of deuterostomes (a superphylum), after the chordates (which include the vertebrates, such as birds, fishes, mammals, and reptiles).
Echinoderms are unique among animals in having bilateral symmetry at the larval stage, but fivefold symmetry (pentamerism, a special type of radial symmetry) as adults.
The echinoderms are important both biologically and geologically. Biologically, there are few other groupings so abundant in the biotic desert of the deep sea, as well as shallower oceans. Most echinoderms are able to regenerate tissue, organs, limbs, and reproduce asexually; in some cases, they can undergo complete regeneration from a single limb. Geologically, the value of echinoderms is in their ossified skeletons, which are major contributors to many limestone formations, and can provide valuable clues as to the geological environment. They were the most used species in regenerative research in the 19th and 20th centuries. Further, it is held by some scientists that the radiation of echinoderms was responsible for the Mesozoic Marine Revolution.
Aside from the hard-to-classify Arkarua (a Precambrian animal with echinoderm-like pentamerous radial symmetry), the first definitive members of the phylum appeared near the start of the Cambrian.
== Marine molluscs ==
Molluscs (Latin for soft) form a phylum with about 85,000 extant recognized species. By species count they are the largest marine phylum, comprising about 23% of all the named marine organisms. Molluscs have more varied forms than other invertebrate phyla. They are highly diverse, not just in size and in anatomical structure, but also in behaviour and in habitat. The majority of species still live in the oceans, from the seashores to the abyssal zone, but some form a significant part of the freshwater fauna and the terrestrial ecosystems.
The mollusc phylum is divided into nine or ten taxonomic classes, two of which are extinct. These classes include gastropods, bivalves and cephalopods, as well as other lesser-known but distinctive classes. Gastropods with protective shells are referred to as snails (sea snails), whereas gastropods without protective shells are referred to as slugs (sea slugs). Gastropods are by far the most numerous molluscs in terms of classified species, accounting for 80% of the total. Bivalves include clams, oysters, cockles, mussels, scallops, and numerous other families. There are about 8,000 marine bivalves species (including brackish water and estuarine species), and about 1,200 freshwater species. Cephalopod include octopus, squid and cuttlefish. They are found in all oceans, and neurologically are the most advanced of the invertebrates. About 800 living species of marine cephalopods have been identified, and an estimated 11,000 extinct taxa have been described. There are no fully freshwater cephalopods.
Molluscs have such diverse shapes that many textbooks base their descriptions of molluscan anatomy on a generalized or hypothetical ancestral mollusc. This generalized mollusc is unsegmented and bilaterally symmetrical with an underside consisting of a single muscular foot.: 484–628 Beyond that it has three further key features. Firstly, it has a muscular cloak called a mantle covering its viscera and containing a significant cavity used for breathing and excretion. A shell secreted by the mantle covers the upper surface. Secondly (apart from bivalves) it has a rasping tongue called a radula used for feeding. Thirdly, it has a nervous system including a complex digestive system using microscopic, muscle-powered hairs called cilia to exude mucus. The generalized mollusc has two paired nerve cords (three in bivalves). The brain, in species that have one, encircles the esophagus. Most molluscs have eyes and all have sensors detecting chemicals, vibrations, and touch. The simplest type of molluscan reproductive system relies on external fertilization, but more complex variations occur. All produce eggs, from which may emerge trochophore larvae, more complex veliger larvae, or miniature adults. The depiction is rather similar to modern monoplacophorans, and some suggest it may resemble very early molluscs.: 284–291 : 298–300
Good evidence exists for the appearance of marine gastropods, cephalopods and bivalves in the Cambrian period 538.8 to 486.85 million years ago. However, the evolutionary history both of molluscs' emergence from the ancestral Lophotrochozoa and of their diversification into the well-known living and fossil forms are still subjects of vigorous debate among scientists.
== Marine arthropods ==
Arthropods (Greek for jointed feet) have an exoskeleton (external skeleton), a segmented body, and jointed appendages (paired appendages). They form a phylum which includes insects, arachnids, myriapods, and crustaceans. Arthropods are characterized by their jointed limbs and cuticle made of chitin, often mineralised with calcium carbonate. The arthropod body plan consists of segments, each with a pair of appendages. The rigid cuticle inhibits growth, so arthropods replace it periodically by moulting. Their versatility has enabled them to become the most species-rich members of all ecological guilds in most environments.
Marine arthropods range in size from the microscopic crustacean Stygotantulus to the Japanese spider crab. Arthropods' primary internal cavity is a hemocoel, which accommodates their internal organs, and through which their haemolymph - analogue of blood - circulates; they have open circulatory systems. Like their exteriors, the internal organs of arthropods are generally built of repeated segments. Their nervous system is "ladder-like", with paired ventral nerve cords running through all segments and forming paired ganglia in each segment. Their heads are formed by fusion of varying numbers of segments, and their brains are formed by fusion of the ganglia of these segments and encircle the esophagus. The respiratory and excretory systems of arthropods vary, depending as much on their environment as on the subphylum to which they belong.
Their vision relies on various combinations of compound eyes and pigment-pit ocelli: in most species the ocelli can only detect the direction from which light is coming, and the compound eyes are the main source of information, but the main eyes of spiders are ocelli that can form images and, in a few cases, can swivel to track prey. Arthropods also have a wide range of chemical and mechanical sensors, mostly based on modifications of the many setae (bristles) that project through their cuticles. Arthropods' methods of reproduction and development are diverse; all terrestrial species use internal fertilization, but this is often by indirect transfer of the sperm via an appendage or the ground, rather than by direct injection. Marine species all lay eggs and use either internal or external fertilization. Arthropod hatchlings vary from miniature adults to grubs that lack jointed limbs and eventually undergo a total metamorphosis to produce the adult form.
Crustaceans
The evolutionary ancestry of arthropods dates back to the Cambrian Period. The group is generally regarded as monophyletic, and many analyses support the placement of arthropods with cycloneuralians (or their constituent clades) in a superphylum Ecdysozoa. Overall however, the basal relationships of Metazoa are not yet well resolved. Likewise, the relationships between various arthropod groups are still actively debated.
== Other phyla ==
Tardigrada, Lobopodia, (Onychophora)
Non-craniate (non-vertebrate) chordates: Cephalochordata, Tunicata and Haikouella. These invertebrates are close relatives of the vertebrates.
Non-craniate chordates are close relatives of vertebrates
== Minerals from sea water ==
There are a number of marine invertebrates that use minerals that are present in the sea in such minute quantities that they were undetectable until the advent of spectroscopy. Vanadium is concentrated by some tunicates for use in their blood cells to a level ten million times that of the surrounding seawater. Other tunicates similarly concentrate niobium and tantalum.: 947 Lobsters use copper in their respiratory pigment hemocyanin, despite the proportion of this metal in seawater being minute.: 638 Although these elements are present in vast quantities in the ocean, their extraction by man is not economic.
== Glass models ==
Blaschka glass marine invertebrates, 1863–1880
== See also ==
Marine life
Marine biology
Marine vertebrate
List of marine aquarium invertebrate species
Wiwaxia
== Notes ==
== References ==
== Other references ==
List of Animal Phyla | Wikipedia/Marine_invertebrates |
A demyelinating disease refers to any disease affecting the nervous system where the myelin sheath surrounding neurons is damaged. This damage disrupts the transmission of signals through the affected nerves, resulting in a decrease in their conduction ability. Consequently, this reduction in conduction can lead to deficiencies in sensation, movement, cognition, or other functions depending on the nerves affected.
Various factors can contribute to the development of demyelinating diseases, including genetic predisposition, infectious agents, autoimmune reactions, and other unknown factors. Proposed causes of demyelination include genetic predisposition, environmental factors such as viral infections or exposure to certain chemicals. Additionally, exposure to commercial insecticides like sheep dip, weed killers, and flea treatment preparations for pets, which contain organophosphates, can also lead to nerve demyelination. Chronic exposure to neuroleptic medications may also cause demyelination. Furthermore, deficiencies in vitamin B12 can result in dysmyelination.
Demyelinating diseases are traditionally classified into two types: demyelinating myelinoclastic diseases and demyelinating leukodystrophic diseases. In the first group, a healthy and normal myelin is destroyed by toxic substances, chemicals, or autoimmune reactions. In the second group, the myelin is inherently abnormal and undergoes degeneration. The Poser criteria named this second group dysmyelinating diseases.
In the most well-known demyelinating disease, multiple sclerosis, evidence suggests that the body's immune system plays a significant role. Acquired immune system cells, specifically T-cells, are found at the site of lesions. Other immune system cells, such as macrophages (and possibly mast cells), also contribute to the damage.
== Signs and symptoms ==
Symptoms and signs that present in demyelinating diseases are different for each condition. These symptoms and signs can present in a person with a demyelinating disease:
== Evolutionary considerations ==
The role of prolonged cortical myelination in human evolution has been implicated as a contributing factor in some cases of demyelinating disease. Unlike other primates, humans exhibit a unique pattern of postpubertal myelination, which may contribute to the development of psychiatric disorders and neurodegenerative diseases that present in early adulthood and beyond. The extended period of cortical myelination in humans may allow greater opportunities for disruption in myelination, resulting in the onset of demyelinating disease. Furthermore, humans have significantly greater prefrontal white matter volume than other primate species, which implies greater myelin density. Increased myelin density in humans as a result of a prolonged myelination may, therefore, structure risk for myelin degeneration and dysfunction. Evolutionary considerations for the role of prolonged cortical myelination as a risk factor for demyelinating disease are particularly pertinent given that genetics and autoimmune deficiency hypotheses fail to explain many cases of demyelinating disease. As has been argued, diseases such as multiple sclerosis cannot be accounted for by autoimmune deficiency alone, but strongly imply the influence of flawed developmental processes in disease pathogenesis. Therefore, the role of the human-specific prolonged period of cortical myelination is an important evolutionary consideration in the pathogenesis of demyelinating disease.
== Diagnosis ==
Various methods/techniques are used to diagnose demyelinating diseases:
Exclusion of other conditions that have overlapping symptoms
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to visualize internal structures of the body in detail. MRI makes use of the property of nuclear magnetic resonance (NMR) to image nuclei of atoms inside the body. This method is reliable because MRIs assess changes in proton density. "Spots" can occur as a result of changes in brain water content.: 113
Evoked potential is an electrical potential recorded from the nervous system following the presentation of a stimulus as detected by electroencephalography (EEG), electromyography (EMG), or other electrophysiological recording method.: 117
Cerebrospinal fluid analysis (CSF) can be extremely beneficial in the diagnosis of central nervous system infections. A CSF culture examination may yield the microorganism that caused the infection.
Quantitative proton magnetic resonance spectroscopy (MRS) is a noninvasive analytical technique that has been used to study metabolic changes in brain tumors, strokes, seizure disorders, Alzheimer's disease, depression, and other diseases affecting the brain. It has also been used to study the metabolism of other organs such as muscles.: 309
Diagnostic criteria refers to a specific combination of signs, symptoms, and test results that the clinician uses in an attempt to determine the correct diagnosis.: 320
Fluid-attenuated inversion recovery (FLAIR) uses a pulse sequence to suppress cerebrospinal fluid and show lesions more clearly, and is used for example in multiple sclerosis evaluation.
=== Types ===
Demyelinating diseases can be divided in those affecting the central nervous system (CNS) and those affecting the peripheral nervous system (PNS). They can also be classified by the presence or absence of inflammation. Finally, a division may be made based on the underlying cause of demyelination: the disease process can be demyelinating myelinoclastic, wherein myelin is destroyed; or dysmyelinating leukodystrophic, wherein myelin is abnormal and degenerative.
==== CNS ====
The demyelinating disorders of the central nervous system include:
Myelinoclastic or demyelinating disorders:
Typical forms of multiple sclerosis
Neuromyelitis optica, or Devic's disease
Idiopathic inflammatory demyelinating diseases
Leukodystrophic or dysmyelinating disorders:
CNS neuropathies such as those produced by vitamin B12 deficiency
Central pontine myelinolysis
Myelopathies such as tabes dorsalis (syphilitic myelopathy)
Leukoencephalopathies such as progressive multifocal leukoencephalopathy
Leukodystrophies
The myelinoclastic disorders are typically associated with symptoms such as optic neuritis and transverse myelitis, because the demyelinating inflammation can affect the optic nerve or spinal cord. Many are idiopathic. Both myelinoclastic and leukodystrophic modes of disease may result in lesional demyelinations of the central nervous system.
==== PNS ====
The demyelinating diseases of the peripheral nervous system include:
Guillain–Barré syndrome and its chronic counterpart, chronic inflammatory demyelinating polyneuropathy
Anti-MAG peripheral neuropathy
Charcot–Marie–Tooth disease and its counterpart Hereditary neuropathy with liability to pressure palsy
Copper deficiency-associated conditions (peripheral neuropathy, myelopathy, and rarely optic neuropathy)
Progressive inflammatory neuropathy
== Treatment ==
Treatments are patient-specific and depend on the symptoms that present with the disorder, as well as the progression of the condition. Improvements to the patient's life may be accomplished through the management of symptoms or slowing of the rate of demyelination. Treatment can include medication, lifestyle changes (i.e. smoking cessation, increased rest, and dietary changes), counselling, relaxation, physical exercise, patient education, and in some cases, deep brain thalamic stimulation (to ameliorate tremors).: 227–248
== Prognosis ==
Prognosis depends on the condition itself. Some conditions such as MS depend on the subtype of the disease and various attributes of the patient such as age, sex, initial symptoms, and the degree of disability the patient experiences. Life expectancy in MS patients is 5 to 10 years lower than unaffected people. MS is an inflammatory demyelinating disease of the central nervous system (CNS) that develops in genetically susceptible individuals after exposure to unknown environmental trigger(s). The bases for MS are unknown but are strongly suspected to involve immune reactions against autoantigens, particularly myelin proteins. The most accepted hypothesis is that dialogue between T-cell receptors and myelin antigens leads to an immune attack on the myelin-oligodendrocyte complex. These interactions between active T cells and myelin antigens provoke a massive destructive inflammatory response and promote continuing proliferation of T and B cells and macrophage activation, which sustains secretion of inflammatory mediators. Other conditions such as central pontine myelinolysis have about a third of patients recover and the other two-thirds experience varying degrees of disability. In some cases, such as transverse myelitis, the patient can begin recovery as early as 2 to 12 weeks after the onset of the condition.
== Epidemiology ==
Incidence of demyelinating diseases varies by disorder. Some conditions, such as tabes dorsalis appear predominantly in males and begin in midlife. Optic neuritis, though, occurs preferentially in females typically between the ages of 30 and 35. Other conditions such as multiple sclerosis vary in prevalence depending on the country and population. This condition can appear in children and adults.
== Research ==
Much of the research conducted on demyelinating diseases is targeted towards discovering the mechanisms by which these disorders function in an attempt to develop therapies and treatments for individuals affected by these conditions. For example, proteomics has revealed several proteins which contribute to the pathophysiology of demyelinating diseases.
For example, COX-2 has been implicated in oligodendrocyte death in animal models of demyelination.
The presence of myelin debris has been correlated with damaging inflammation as well as poor regeneration, due to the presence of inhibitory myelin components.
N-cadherin is expressed in regions of active remyelination and may play an important role in generating a local environment conducive to remyelination. N-cadherin agonists have been identified and observed to stimulate neurite growth and cell migration, key aspects of promoting axon growth and remyelination after injury or disease.
Immunomodulatory drugs such as fingolimod have been shown to reduce immune-mediated damage to the CNS, preventing further damage in patients with MS. The drug targets the role of macrophages in disease progression.
Manipulating thyroid hormone levels may become a viable strategy to promote remyelination and prevent irreversible damage in MS patients.
It has also been shown that intranasal administration of apotransferrin (aTf) can protect myelin and induce remyelination.
Finally, electrical stimulation which activates neural stem cells may provide a method by which regions of demyelination can be repaired.
== In other animals ==
Demyelinating diseases/disorders have been found worldwide in various animals. Some of these animals include mice, pigs, cattle, hamsters, rats, sheep, Siamese kittens, and a number of dog breeds (including Chow Chow, Springer Spaniel, Dalmatian, Samoyed, Golden Retriever, Lurcher, Bernese Mountain Dog, Vizsla, Weimaraner, Australian Silky Terrier, and mixed breeds).
== See also ==
Degenerative disease
Multiple sclerosis borderline
The Lesion Project (multiple sclerosis)
The Myelin Project
Myelin Repair Foundation
== References ==
== External links == | Wikipedia/Demyelinating_disease |
Non-spiking neurons are neurons that are located in the central and peripheral nervous systems and function as intermediary relays for sensory-motor neurons. They do not exhibit the characteristic spiking behavior of action potential generating neurons.
Non-spiking neural networks are integrated with spiking neural networks to have a synergistic effect in being able to stimulate some sensory or motor response while also being able to modulate the response.
== Discovery ==
=== Animal models ===
There are an abundance of neurons that propagate signals via action potentials and the mechanics of this particular kind of transmission is well understood. Spiking neurons exhibit action potentials as a result of a neuron characteristic known as membrane potential. Through studying these complex spiking networks in animals, a neuron that did not exhibit characteristic spiking behavior was discovered. These neurons use a graded potential to transmit data as they lack the membrane potential that spiking neurons possess. This method of transmission has a huge effect on the fidelity, strength, and lifetime of the signal. Non-spiking neurons were identified as a special kind of interneuron and function as an intermediary point of process for sensory-motor systems. Animals have become substantial models for understanding more about non-spiking neural networks and the role they play in an animal’s ability to process information and its overall function. Animal models indicate that the interneurons modulate directional and posture coordinating behaviors.
Crustaceans and arthropods such as the crawfish have created many opportunities to learn about the modulatory role that these neurons have in addition to their potential to be modulated regardless of their lack of exhibiting spiking behavior. Most of the known information about nonspiking neurons is derived from animal models. Studies focus on neuromuscular junctions and modulation of abdominal motor cells. Modulatory interneurons are neurons that are physically situated next to muscle fibers and innervate the nerve fibers which allow for some orienting movement. These modulatory interneurons are usually nonspiking neurons. Advances in studying nonspiking neurons included determining new delineations among the different types of interneurons. These discoveries were due to the usage of methods such as protein receptor silencing. Studies have been done on the non-spiking neuron qualities in animals of specific non-spiking neural networks that have a corollary in humans, e.g. retina amacrine cell of the eye.
== Physiology ==
=== Definition ===
A non-spiking neuron is a neuron that transmits a signal via graded potential. The rate of subsequent neurotransmitter release is linearly correlated with the magnitude and sign of summed inputs which allows them to preserve specific features of the eliciting stimulus, such as light quanta information by photoreceptors. They are a fundamental component of visual processing in the retina. They can be more susceptible to noise. Studies show that these neurons may offer a contribution to learning and modulation of motor neuron networks.
Spiking neurons and non-spiking neurons are usually integrated into the same neural network, but they possess specific characteristics. The major difference between these two neuron types is the manner in which encoded information is propagated along a length to the central nervous system or to some locus of interneurons, such as a neuromuscular junction. Non-spiking neurons propagate messages without eliciting an action potential. This is most likely due to the chemical composition of the membranes of the non-spiking neurons. They lack protein channels for sodium and are more sensitive to certain neurotransmitters. They function by propagating graded potentials and serve to modulate some neuromuscular junctions. Spiking neurons are noted as traditional action potential generating neurons.
=== Identification ===
"Interneurons" is a name used to indicate neurons that are neither sensory neurons nor motor neurons, but function as an intermediary processing and transmission state for signals that have been received via dorsal root ganglia cells. A large amount of these interneurons seem to exhibit the non-spiking characteristic. To better define non-spiking neuron signal transmission and signal transduction, many experiments have been performed to qualify and quantify the fidelity, speed, and mechanics of signal transmission in non-spiking neurons. There have been classifications based on the larger group "interneurons" where pre-motor nonspiking neurons are referred to as postlateral (PL) or anteriolateral (AL) interneurons, with AL interneurons divided into three types of interneurons based on staining. The initial differentiation between PL and AL interneurons are their responses to GABA, a neurotransmitter for muscle tone. They also have different staining responses permitting quick and qualified classification.
=== Cell types ===
Many of the nonspiking neurons are found near neuromuscular junctions and exist as long fibers that help to innervate certain motor nerves such as the thoracic-coxal
muscle receptor organ (TCMRO) of a crab. They function in a modulatory role by helping to establish posture and directional behavior. This was intensely modeled in the crustacean and in insects showing how appendages are oriented via these nonspiking neural pathways. Amacrine cells are another major type of non-spiking neuron and their lifetime involves the conversion to a non-spiking neuron from a spiking neuron once the retina obtains maturity. They are one of the first cells to differentiate during prenatal development. Upon the opening of the eyes, these cells begin to shed their sodium ion channels and become non-spiking neurons. It was hypothesized that the reason for its establishment as a spiking neuron was to help with the maturation of the retina by the usage of action potentials themselves, and not necessarily the information the action potential carried. This was supported with the occurrence of synchronous firing by the starburst amacrine cells during the initial stages of development. This study used a rabbit model. However, spiking wide field amacrine cells have been identified in the adult rabbit retina. These cells extend processes spanning >1mm across the retina and actively propagate dendritic spikes to and from the soma Additionally, a spiking GABAergic nitric oxide producing amacrine cell type (nNOS-1 AC) has been identified in mice and is thought to play a role in precise feature extraction from light through a range of noisy background luminance.
=== Physiological characteristics ===
Some studies have indicated that even with the volatility of signal transmission with these particular neurons, they still perform very well in maintaining signal strength. Studies show that the ratio of signal to noise in experimental settings of some signals are at least 1000 and upwards to 10000 over 5-7mm of propagation length by nerves.
These interneurons are connected to one another via synapses and a minority, approximately 15% of the neurons, exhibit bidirectional capacity and were excitatory. About 77% of these neurons indicated a one-way mode of transmitting signals which were inhibitory in nature. These numbers were modeled from an arthropod as pre-motor elements in the motor control system. They were located in the abdominal region. Synapses are known as gaps between neurons which facilitate the spread of a message via neurotransmitters that may excite or depress the subsequent neuron through a complex cascade of electrochemical events. For the interneurons exhibiting one-way signaling, they would receive an excitatory stimulus, experimentally, and the post-synaptic cell was given an inhibitory signal. The interaction between the two cells was modulatory in which the pre-synaptic cell with the initial excitatory signal would mediate the postsynaptic cell even after being inhibited. Signal amplitude was used to determine the effects of the modulation on the signal transmission.
The speed of signal transmission at 200 Hz, the most conserved bandwidth of signal transmission for non-spiking neurons, was approximately 2500 bits/second in which there was a 10-15% decrease in speed as the signal propagated down the axon. A spiking neuron compares at 200bits/ second, but reconstruction is greater and there is less influence by noise. There are other non-spiking neurons that exhibit conserved signal transmission at other bandwidths.
While some non-spiking neurons are specifically involved in neuromuscular modulation, studying amacrine cells has created opportunities to discuss the role of non-spiking neurons in neuroplasticity. Since amacrine cells, which are a type of non-spiking neurons, undergo a transformation from spiking to non-spiking cells, there have been many studies that try to identify the functional reasons for such a transformation. Starburst amacrine cells use action potentials during retinal development, and once the retina is mature, these cells transform into non-spiking neurons. The change from a cell that can generate action potentials to solely functioning off of a graded potential is drastic, and may provide insight into why the two kinds of neural networks exist. The cells lose sodium channels. The loss of the sodium channels is triggered by the opening of the eye correlating to the possibility of the environment playing a crucial role in determination of neural cell types. The rabbit animal model was used to develop this particular study. This transition is not quite understood but heavily concludes that the spiking and non-spiking statuses occupied by the starburst amacrine cells are vital to the maturation of the eyes.
== Functions ==
=== Modulation ===
By using known neurotransmitters that affect non-spiking neurons, modeled neural networks may be modified to either ease neuromuscular hyperactivity, or cells themselves may be transformed to be able to provide stronger signals. A calcium transporter study indicates the effect that protein channels have on the overall fidelity and firing capacity of the non-spiking neurons. Since most of the propagated messages are based on a proportionality constant, meaning, there is not a temporal or spatial significance to the presynaptic firing, these signals literally "repeat what they have been told". When it comes down to chemical systems in the body, a non-spiking neural network is definitely an area of exploration. The amacrine cell study poses new and exciting components to the study of altering the chemical and mechanical properties of the non-spiking neural networks.
=== Memory and learning ===
Very little is known about the application of these networks to memory and learning. There are indications that spiking and nonspiking networks both play a vital role in memory and learning. Research has been conducted with the use of learning algorithms, microelectrode arrays, and hybrots. By studying how neurons transfer information, it becomes more possible to enhance those model neural networks and better define what clear information streams could be presented. Perhaps, by conjoining this study with the many neurotrophic factors present, neural networks could be manipulated for optimal routing, and consequently optimal learning.
=== Device production ===
By studying the nonspiking neuron, the field of neuroscience has benefited by having workable models that indicate how information is propagated through a neural network. This allows for the discussion of the factors that influence how networks work, and how they may be manipulated. Non-spiking neurons seem to be more sensitive to interference given that they exhibit graded potentials. So for non-spiking neurons, any stimulus will elicit a response, whereas spiking neurons exhibit action potentials which function as an "all or none" entity.
In biomedical engineering, it is a priority to understand the biological contributions to an overall system in order to understand how the systems may be optimized. Paul Bach y Rita was a famous believer of neuroplasticity and integrated the principles of device design in order to model what neurons were actually doing in the brain and create a device that simulated functions already prescribed by the biological system itself. Some special advances made in the medical field based on structured models of biological systems include the cochlear implant, practices encouraged by Dr. VS Ramachandran on phantom limbs and other optical applications, and other devices that simulate electrical impulses for sensory signal transduction. By continuing to achieve a workable model of the non-spiking neural network, its applications will become evident.
== See also ==
Transduction (biophysics)
EPSP (excitatory post-synaptic potential)
IPSP (inhibitory post-synaptic potential)
== References == | Wikipedia/Non-spiking_neurons |
A motor neuron (or motoneuron), also known as efferent neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly control effector organs, mainly muscles and glands. There are two types of motor neuron – upper motor neurons and lower motor neurons. Axons from upper motor neurons synapse onto interneurons in the spinal cord and occasionally directly onto lower motor neurons. The axons from the lower motor neurons are efferent nerve fibers that carry signals from the spinal cord to the effectors. Types of lower motor neurons are alpha motor neurons, beta motor neurons, and gamma motor neurons.
A single motor neuron may innervate many muscle fibres and a muscle fibre can undergo many action potentials in the time taken for a single muscle twitch. Innervation takes place at a neuromuscular junction and twitches can become superimposed as a result of summation or a tetanic contraction. Individual twitches can become indistinguishable, and tension rises smoothly eventually reaching a plateau.
Although the word "motor neuron" suggests that there is a single kind of neuron that controls movement, this is not the case. Indeed, upper and lower motor neurons—which differ greatly in their origins, synapse locations, routes, neurotransmitters, and lesion characteristics—are included in the same classification as "motor neurons." Essentially, motor neurons, also known as motoneurons, are made up of a variety of intricate, finely tuned circuits found throughout the body that innervate effector muscles and glands to enable both voluntary and involuntary motions. Two motor neurons come together to form a two-neuron circuit. While lower motor neurons start in the spinal cord and go to innervate muscles and glands all throughout the body, upper motor neurons originate in the cerebral cortex and travel to the brain stem or spinal cord. It is essential to comprehend the distinctions between upper and lower motor neurons as well as the routes they follow in order to effectively detect these neuronal injuries and localise the lesions.
== Development ==
Motor neurons begin to develop early in embryonic development, and motor function continues to develop well into childhood. In the neural tube cells are specified to either the rostral-caudal axis or ventral-dorsal axis. The axons of motor neurons begin to appear in the fourth week of development from the ventral region of the ventral-dorsal axis (the basal plate). This homeodomain is known as the motor neural progenitor domain (pMN). Transcription factors here include Pax6, OLIG2, Nkx-6.1, and Nkx-6.2, which are regulated by sonic hedgehog (Shh). The OLIG2 gene being the most important due to its role in promoting Ngn2 expression, a gene that causes cell cycle exiting as well as promoting further transcription factors associated with motor neuron development.
Further specification of motor neurons occurs when retinoic acid, fibroblast growth factor, Wnts, and TGFb, are integrated into the various Hox transcription factors. There are 13 Hox transcription factors and along with the signals, determine whether a motor neuron will be more rostral or caudal in character. In the spinal column, Hox 4-11 sort motor neurons to one of the five motor columns.
== Anatomy and physiology ==
=== Upper motor neurons ===
Upper motor neurons originate in the motor cortex located in the precentral gyrus. The cells that make up the primary motor cortex are Betz cells, which are giant pyramidal cells. The axons of these cells descend from the cortex to form the corticospinal tract. Corticomotorneurons project from the primary cortex directly onto motor neurons in the ventral horn of the spinal cord. Their axons synapse on the spinal motor neurons of multiple muscles as well as on spinal interneurons. They are unique to primates and it has been suggested that their function is the adaptive control of the hands including the relatively independent control of individual fingers. Corticomotorneurons have so far only been found in the primary motor cortex and not in secondary motor areas.
=== Nerve tracts ===
Nerve tracts are bundles of axons as white matter, that carry action potentials to their effectors. In the spinal cord these descending tracts carry impulses from different regions. These tracts also serve as the place of origin for lower motor neurons. There are seven major descending motor tracts to be found in the spinal cord:
Lateral corticospinal tract
Rubrospinal tract
Lateral reticulospinal tract
Vestibulospinal tract
Medial reticulospinal tract
Tectospinal tract
Anterior corticospinal tract
=== Lower motor neurons ===
Lower motor neurons are those that originate in the spinal cord and directly or indirectly innervate effector targets. The target of these neurons varies, but in the somatic nervous system the target will be some sort of muscle fiber. There are three primary categories of lower motor neurons, which can be further divided in sub-categories.
According to their targets, motor neurons are classified into three broad categories:
Somatic motor neurons
Special visceral motor neurons
General visceral motor neurons
==== Somatic motor neurons ====
Somatic motor neurons originate in the central nervous system, project their axons to skeletal muscles (such as the muscles of the limbs, abdominal, and intercostal muscles), which are involved in locomotion. The three types of these neurons are the alpha efferent neurons, beta efferent neurons, and gamma efferent neurons. They are called efferent to indicate the flow of information from the central nervous system (CNS) to the periphery.
Alpha motor neurons innervate extrafusal muscle fibers, which are the main force-generating component of a muscle. Their cell bodies are in the ventral horn of the spinal cord and they are sometimes called ventral horn cells. A single motor neuron may synapse with 150 muscle fibers on average. The motor neuron and all of the muscle fibers to which it connects is a motor unit. Motor units are split up into 3 categories:
Slow (S) motor units stimulate small muscle fibers, which contract very slowly and provide small amounts of energy but are very resistant to fatigue, so they are used to sustain muscular contraction, such as keeping the body upright. They gain their energy via oxidative means and hence require oxygen. They are also called red fibers.
Fast fatiguing (FF) motor units stimulate larger muscle groups, which apply large amounts of force but fatigue very quickly. They are used for tasks that require large brief bursts of energy, such as jumping or running. They gain their energy via glycolytic means and hence do not require oxygen. They are called white fibers.
Fast fatigue-resistant motor units stimulate moderate-sized muscles groups that do not react as fast as the FF motor units, but can be sustained much longer (as implied by the name) and provide more force than S motor units. These use both oxidative and glycolytic means to gain energy.
In addition to voluntary skeletal muscle contraction, alpha motor neurons also contribute to muscle tone, the continuous force generated by noncontracting muscle to oppose stretching. When a muscle is stretched, sensory neurons within the muscle spindle detect the degree of stretch and send a signal to the CNS. The CNS activates alpha motor neurons in the spinal cord, which cause extrafusal muscle fibers to contract and thereby resist further stretching. This process is also called the stretch reflex.
Beta motor neurons innervate intrafusal muscle fibers of muscle spindles, with collaterals to extrafusal fibres. There are two types of beta motor neurons: Slow Contracting- These innervate extrafusal fibers. Fast Contracting- These innervate intrafusal fibers.
Gamma motor neurons innervate intrafusal muscle fibers found within the muscle spindle. They regulate the sensitivity of the spindle to muscle stretching. With activation of gamma neurons, intrafusal muscle fibers contract so that only a small stretch is required to activate spindle sensory neurons and the stretch reflex. There are two types of gamma motor neurons: Dynamic- These focus on Bag1 fibers and enhance dynamic sensitivity. Static- These focus on Bag2 fibers and enhance stretch sensitivity.
Regulatory factors of lower motor neurons
Size Principle – this relates to the soma of the motor neuron. This restricts larger neurons to receive a larger excitatory signal in order to stimulate the muscle fibers it innervates. By reducing unnecessary muscle fiber recruitment, the body is able to optimize energy consumption.
Persistent Inward Current (PIC) – recent animal study research has shown that constant flow of ions such as calcium and sodium through channels in the soma and dendrites influence the synaptic input. An alternate way to think of this is that the post-synaptic neuron is being primed before receiving an impulse.
After Hyper-polarization (AHP) – A trend has been identified that shows slow motor neurons to have more intense AHPs for a longer duration. One way to remember this is that slow muscle fibers can contract for longer, so it makes sense that their corresponding motor neurons fire at a slower rate.
==== Special visceral motor neurons ====
These are also known as branchial motor neurons, which are involved in facial expression, mastication, phonation, and swallowing. Associated cranial nerves are the oculomotor, abducens, trochlear, and hypoglossal nerves.
==== General visceral motor neurons ====
These motor neurons indirectly innervate cardiac muscle and smooth muscles of the viscera ( the muscles of the arteries): they synapse onto neurons located in ganglia of the autonomic nervous system (sympathetic and parasympathetic), located in the peripheral nervous system (PNS), which themselves directly innervate visceral muscles (and also some gland cells).
In consequence, the motor command of skeletal and branchial muscles is monosynaptic involving only one motor neuron, either somatic or branchial, which synapses onto the muscle. Comparatively, the command of visceral muscles is disynaptic involving two neurons: the general visceral motor neuron, located in the CNS, synapses onto a ganglionic neuron, located in the PNS, which synapses onto the muscle.
All vertebrate motor neurons are cholinergic, that is, they release the neurotransmitter acetylcholine. Parasympathetic ganglionic neurons are also cholinergic, whereas most sympathetic ganglionic neurons are noradrenergic, that is, they release the neurotransmitter noradrenaline. (see Table)
=== Neuromuscular junctions ===
A single motor neuron may innervate many muscle fibres and a muscle fibre can undergo many action potentials in the time taken for a single muscle twitch. As a result, if an action potential arrives before a twitch has completed, the twitches can superimpose on one another, either through summation or a tetanic contraction. In summation, the muscle is stimulated repetitively such that additional action potentials coming from the somatic nervous system arrive before the end of the twitch. The twitches thus superimpose on one another, leading to a force greater than that of a single twitch. A tetanic contraction is caused by constant, very high frequency stimulation - the action potentials come at such a rapid rate that individual twitches are indistinguishable, and tension rises smoothly eventually reaching a plateau.
The interface between a motor neuron and muscle fiber is a specialized synapse called the neuromuscular junction. Upon adequate stimulation, the motor neuron releases a flood of acetylcholine (Ach) neurotransmitters from synaptic vesicles bound to the plasma membrane of the axon terminals. The acetylcholine molecules bind to postsynaptic receptors found within the motor end plate. Once two acetylcholine receptors have been bound, an ion channel is opened and sodium ions are allowed to flow into the cell. The influx of sodium into the cell causes depolarization and triggers a muscle action potential. T tubules of the sarcolemma are then stimulated to elicit calcium ion release from the sarcoplasmic reticulum. It is this chemical release that causes the target muscle fiber to contract.
In invertebrates, depending on the neurotransmitter released and the type of receptor it binds, the response in the muscle fiber could be either excitatory or inhibitory. For vertebrates, however, the response of a muscle fiber to a neurotransmitter can only be excitatory, in other words, contractile. Muscle relaxation and inhibition of muscle contraction in vertebrates is obtained only by inhibition of the motor neuron itself. This is how muscle relaxants work by acting on the motor neurons that innervate muscles (by decreasing their electrophysiological activity) or on cholinergic neuromuscular junctions, rather than on the muscles themselves.
=== Synaptic input to motor neurons ===
Motor neurons receive synaptic input from premotor neurons. Premotor neurons can be 1) spinal interneurons that have cell bodies in the spinal cord, 2) sensory neurons that convey information from the periphery and synapse directly onto motoneurons, 3) descending neurons that convey information from the brain and brainstem. The synapses can be excitatory, inhibitory, electrical, or neuromodulatory. For any given motor neuron, determining the relative contribution of different input sources is difficult, but advances in connectomics have made it possible for fruit fly motor neurons. In the fly, motor neurons controlling the legs and wings are found in the ventral nerve cord, homologous to the spinal cord. Fly motor neurons vary by over 100X in the total number of input synapses. However, each motor neuron gets similar fractions of its synapses from each premotor source: ~70% from neurons within the VNC, ~10% from descending neurons, ~3% from sensory neurons, and ~6% from VNC neurons that also send a process up to the brain. The remaining 10% of synapses come from neuronal fragments that are unidentified by current image segmentation algorithms and require additional manual segmentation to measure.
== See also ==
Betz cell
Central chromatolysis
Motor dysfunction
Motor neuron disease
Nerve
Sensory nerve
Motor nerve
Afferent nerve fiber
Efferent nerve fiber
Sensory neuron
== References ==
== Sources ==
Sherwood, L. (2001). Human Physiology: From Cells to Systems (4th ed.). Pacific Grove, CA: Brooks-Cole. ISBN 0-534-37254-6.
Marieb, E. N.; Mallatt, J. (1997). Human Anatomy (2nd ed.). Menlo Park, CA: Benjamin/Cummings. ISBN 0-8053-4068-8. | Wikipedia/Motoneurons |
Glutamate synthase (also known as Glutamine oxoglutarate aminotransferase) is an enzyme and frequently abbreviated as GOGAT. This enzyme manufactures glutamate from glutamine and α-ketoglutarate, and thus along with glutamine synthetase (abbreviated GS) plays a central role in the regulation of nitrogen assimilation in photosynthetic eukaryotes and prokaryotes. This is of great importance as primary productivity in many marine environments is regulated by the availability of inorganic nitrogen.
The primary sources of inorganic nitrogen used by marine algae are nitrate and ammonium. Both forms are ultimately incorporated into amino acids through the sequential reaction of glutamine synthetase (GS) and glutamate synthase (glutamine:2-oxoglutarate aminotransferase; GOGAT). GOGAT isoenzymes catalyze the transfer of the amido nitrogen of glutamine to 2-oxoglutarate using pyridine nucleotides (NADH-/NADPH-dependent) or ferredoxin (ferredoxin dependent) as reductants. They are called NADH-GOGAT and Fd-GOGAT respectively. In photosynthetic eukaryotes, GS and GOGAT isoenzymes are localized in the cytosol and chloroplast.
Fd-GOGAT is found strictly in cyanobacteria and photosynthetic eukaryotes, and the gene is located in the chloroplast of rhodophytes and in the nucleus of vascular plants, but in both cases its product is active in the chloroplast. NADH-GOGAT is found in the nucleus of vascular plants, fungi, and diatoms, while NADPH-GOGAT is found in non-photosynthetic bacteria and archaea.
== See also ==
Glutamate synthase (NADPH)
Glutamate synthase (NADH)
Glutamate synthase (ferredoxin)
== References == | Wikipedia/Glutamine_oxoglutarate_aminotransferase |
The Neuroscience Information Framework is a repository of global neuroscience web resources, including experimental, clinical, and translational neuroscience databases, knowledge bases, atlases, and genetic/genomic resources and provides many authoritative links throughout the neuroscience portal of Wikipedia.
== Description ==
The Neuroscience Information Framework (NIF) is an initiative of the NIH Blueprint for Neuroscience Research, which was established in 2004 by the National Institutes of Health.
Development of the NIF started in 2008, when the University of California, San Diego School of Medicine obtained an NIH contract to create and maintain "a dynamic inventory of web-based neurosciences data, resources, and tools that scientists and students can access via any computer connected to the Internet". The project is headed by Maryann Martone, co-director of the National Center for Microscopy and Imaging Research (NCMIR), part of the multi-disciplinary Center for Research in Biological Systems (CRBS), headquartered at UC San Diego. Together with co-principal investigators Jeffrey S. Grethe and Amarnath Gupta, Martone leads a national collaboration that includes researchers at Yale University, the California Institute of Technology, George Mason University, Harvard, and Washington University.
== Goals ==
Unlike general search engines, NIF provides much deeper access to a focused set of resources that are relevant to neuroscience, search strategies tailored to neuroscience, and access to content that is traditionally “hidden” from web search engines. The NIF is a dynamic inventory of neuroscience databases, annotated and integrated with a unified system of biomedical terminology (i.e. NeuroLex). NIF supports concept-based queries across multiple scales of biological structure and multiple levels of biological function, making it easier to search for and understand the results. NIF will also provide a registry through which resources providers can disclose availability of resources relevant to neuroscience research. NIF is not intended to be a warehouse or repository itself, but a means for disclosing and locating resources elsewhere available via the web.
The NIFSTD, or NIF Standard Ontology contains many of the terms, synonyms and abbreviations useful for neuroscience, as well as dynamic categories such as defined cell classes based on various properties like neuron by neurotransmitter or by circuit role or drugs of abuse according to the National Institutes on Drug Abuse.
Any term (with associated synonyms) or dynamic category (all terms with their synonyms) can be used to simultaneously query all of the data that NIF currently indexes, please find several examples below:
available data about the hippocampus including synonyms
data about parkinson's disease including archaic synonyms like paralysis agitans
neocortical neuron a dynamic category includes all neurons that have cell soma in any part of the neocortex
== Content ==
NIF content can be thought of as a Catalog (NIF Registry) and deep database search (NIF Data Federation)
The NIF Catalog has the largest listing of NIH-funded, neuroscience-relevant resources, including scientific databases, software tools, experimental reagents and tools, knowledge bases and portals, and other entities identified by the neuroscience research community.
A listing of current resources can be found at www.neuinfo.org/registry
The NIF Data Federation searches deep database content of over 150 databases including: various NCBI databases (PubMed, Gensat, Entrez Gene, Homologene, GEO) as well as many large and small databases that have something to do with neuroscience including Gemma (microarray data from the nervous system), CCDB & CIL (images of neurons and astrocytes, mainly), GeneNetwork, AgingGenesDB, XNAT, 1000 Functional Connectomes. The 'complete' list (as of April 2013) can be found in the table below. An updated list can be found on the Data Federation page.
In addition many databases that have very similar types of data have been integrated into 'virtual databases', which combine many databases into one table. For example, the AntibodyRegistry combines data from 200+ vendors, the NIF Integrated BrainGeneExpression combines gene expression data from Gensat, Alan Brain, and Mouse Genome Informatics, the Connectivity view combines six databases that have statements about nervous system connectivity, the Integrated Animal view combines data about experimental animal catalogs available to researchers from transgenic or inbred worms, zebrafish, mice and rats. We add more of these as data are registered, so check back to this page to see the current contents.
For an exhaustive and up to date list of Databases and Datasets registered to NIF please check this page www.neurolex.org. The table below was updated April 9, 2013.
== Data Via Web Services ==
The idea of NIF is that while scientific databases do have a plethora of interfaces, some quite complex, there should be a uniform way of looking at them and searching though them. This uniform search idea has been extended to services so that developers can take advantage of the work done at NIF to enhance their own applications by gaining access to all of the data available through the NIF interface.
When data is made public via NIF, it also becomes immediately available via web services. These RESTful web services can be thought of as programming functions that can be built into other applications. Currently, the data can be queried and pulled as an XML feed and several other sites are now pulling NIF data via services, including DOMEO and Eagle i. Developers can learn how to access data by viewing the WADL file available at http://neuinfo.org/developers
Below are some public RESTful services that can be accessed by students or used in building applications:
Annotate any text by using this url:
* http://nif-services.neuinfo.org/servicesv1/v1/annotate?content=The%20cerebellum%20is%20a%20wonderful%20thing&longestOnly=true
The url contains the text you want to annotate, the input, which is "The cerebellum is a wonderful thing". To change this you can try to use any other text.
The output from the service will return the sentence with a SPAN tag denoting that it recognized the term cerebellum and it is a type of anatomical_structure. The terms that are not recognized are returned without span tags. Note, the longestOnly=true parameter is optional it means that only the longest set of terms will be recognized an in this example it makes no difference, but in terms like hippocampal neuron it will only return one response.
Developers can use the span tags to bring back information about the recognized term because the identifier is unique and linked to definitions, synonyms, other brain regions and in some cases images:
For a human readable version see
* http://neurolex.org/wiki/Birnlex_1489
For a machine readable version see
* http://nif-services.neuinfo.org/ontoquest/concepts/Birnlex_1489?get_super=true
Retrieve neuroscience auto-complete suggestions, e.g.,
* http://nif-services.neuinfo.org/servicesv1/v1/vocabulary?prefix=hippocampu
The above example shows the term completion for "hippocampu", but you can try to type on the url any other set of letters.
The return of the service is a set of terms that matches this string including: Hippocampus and many hippocampal cells.
Retrieve the registry items that match a search term:
* http://nif-services.neuinfo.org/servicesv1/v1/federation/data/nlx_144509-1?q=miame
The NIF Registry is a data source and this service will return all items in the registry that match the particular search term. In this case the term is miame, as in the miame standard. To use this data retrieving function you can type query terms into the end of this url in addition to or instead of the term miame. This will work the same way as typing your terms into the search box here:
* https://neuinfo.org/mynif/search.php?q=hippocampus&t=registry
Note, make sure to check the terms and conditions for any source of data, terms and conditions are available as a courtesy in NIF, but you may also check with the individual sources that you wish to incorporate in your applications, all of the above described data is owned by NIF and is covered under the Creative Commons Attribution license, so it can be freely distributed and shared.
== Notes and references ==
== See also ==
NeuroLex
NeuroNames
== External links ==
Neuroscience Information Framework (NIF) website
NIF NeuroLex - The Neuroscience Lexicon
Neuroscience Information Framework News & Announcements
Neuroscience Information Framework Facebook Page
Neuroscience Information Framework Mendeley Group | Wikipedia/Neuroscience_Information_Framework |
Beta motor neurons (β motor neurons), also called beta motoneurons, are a few kind of lower motor neuron, along with alpha motor neurons and gamma motor neurons. Beta motor neurons innervate intrafusal fibers of muscle spindles with collaterals to extrafusal fibers - a type of slow twitch fiber. Also, axons of alpha, beta, and gamma motor neurons become myelinated. Moreover, these efferent neurons originate from the anterior grey column of the spinal cord and travel to skeletal muscles. However, the larger diameter alpha motor fibers require higher conduction velocity than beta and gamma.
== Types ==
There are two kinds of beta motor neuron (as gamma motor neuron) that include:
Static beta motor neurons. These motor neurons innervate nuclear chain fibers of muscle spindles, with collaterals to extrafusal muscle fibers.
Dynamic beta motor neurons. The dynamic type innervates nuclear bag fibers of muscle spindles, with collaterals to extrafusal muscle fibers.
Gamma motor neurons innervate only intrafusal fibers of muscle spindles, but extrafusal fibers (i.e. slow and fast fibers) are innervated by alpha motoneurons.
== See also ==
Nerve fiber
Type Ia sensory fiber
Type II sensory fiber
== References ==
Williams & Warwick. Gray's Anatomy. Thirty-seventh edition. Churchill Livingstone. ISBN 0-443-04177-6
https://web.archive.org/web/20100725065352/https://musom.marshall.edu/anatomy/grosshom/Musclesensory.html | Wikipedia/Beta_motor_neuron |
Neurocognitive disorders (NCDs), also known as cognitive disorders (CDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem-solving. Neurocognitive disorders include delirium, mild neurocognitive disorders, and major neurocognitive disorder (also known as dementia). They are defined by deficits in cognitive ability that are acquired (as opposed to developmental), typically represent decline, and may have an underlying brain pathology. The DSM-5 defines six key domains of cognitive function: executive function, learning and memory, perceptual-motor function, language, complex attention, and social cognition.
Although Alzheimer's disease accounts for the majority of cases of neurocognitive disorders, there are various medical conditions that affect mental functions such as memory, thinking, and the ability to reason, including frontotemporal degeneration, Huntington's disease, dementia with Lewy bodies, traumatic brain injury (TBI), Parkinson's disease, prion disease, and dementia/neurocognitive issues due to HIV infection. Neurocognitive disorders are diagnosed as mild and major based on the severity of their symptoms. While anxiety disorders, mood disorders, and psychotic disorders can also have an effect on cognitive and memory functions, they are not classified under neurocognitive disorders because loss of cognitive function is not the primary (causal) symptom. Additionally, developmental disorders such as autism typically have a genetic basis and become apparent at birth or early in life as opposed to the acquired nature of neurocognitive disorders.
Causes vary between the different types of disorders but most include damage to the memory portions of the brain. Treatments depend on how the disorder is caused. Medication and therapies are the most common treatments; however, for some types of disorders such as certain types of amnesia, treatments can suppress the symptoms but there is currently no cure.
== Classifications ==
The previous edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) included a section entitled "Delirium, Dementia and Amnestic and Other Cognitive Disorders," which was revised in DSM-5 to the broader "Neurocognitive Disorders." Neurocognitive disorders are described as those with "a significant impairment of cognition or memory that represents a marked deterioration from a previous level of function". The main principle distinguishing neurocognitive disorders from mood disorders and other psychiatric conditions that involve a cognitive component (i.e. increased lapses in memory noted by patients with depression) is that cognitive decline is the "defining characteristic" of the disorder. Additionally, the term "neurocognitive" was added because these disorders most often have alterations/disfunction in neural physiology (i.e. amyloid plaque build-up in Alzheimer disease). The subsections include delirium, mild neurocognitive disorder, and major neurocognitive disorder.
=== Delirium ===
Delirium is a type of neurocognitive disorder that develops rapidly over a short period of time. Delirium may be described using many other terms, including: encephalopathy, altered mental status, altered level of consciousness, acute mental status change, and brain failure. It is described in the DSM-5 as a fluctuating acute change in mental status with associated changes in cognition, attention, and level of consciousness. The onset of delirium can vary from minutes to hours and sometimes days. However, the course of the delirium typically lasts from a few hours to weeks, depending on the underlying cause. Delirium can also be accompanied by a shift in attention, mood swings, violent or unordinary behaviors, and hallucinations. Additionally, changes in cognition can makes situational awareness and processing new information very difficult for patients. Delirium is most common in hospitalized patients, appearing in 18-35% of patients requiring hospital admission. It is also a diagnosis which can be acquired during hospital stays, typically by elderly patients or those with risk factors of delirium. While it is a common diagnosis, delirium can increase the risk of a longer hospital stay and the risk of complications throughout the hospital stay.
=== Mild neurocognitive disorder ===
Mild neurocognitive disorders, also referred to as mild cognitive impairment (MCI), can be thought of as a middle ground between normal aging and major neurocognitive disorder. Unlike delirium, mild neurocognitive disorders tend to develop slowly and are characterized by a progressive memory loss which may or may not progress to major neurocognitive disorder. Studies have shown that between 5-17% of patients with mild cognitive disorder will progress to major neurocognitive disorder each year. The likelihood of developing mild neurocognitive disorder increases with age, affecting 10-20% of adults ages 65 and older. Men also seem to be at a higher risk of developing mild neurocognitive disorder. In addition to memory loss and cognitive impairment, other symptoms include aphasia, apraxia, agnosia, loss of abstract thought, behavioral/personality changes, and impaired judgment.
=== Major neurocognitive disorder ===
Mild and major neurocognitive disorders are differentiated based on the severity of their symptoms. Also still known as dementia, major neurocognitive disorder is characterized by significant cognitive decline and interference with independence, while mild neurocognitive disorder is characterized by moderate cognitive decline and does not interfere with independence. To be diagnosed, it must not be due to delirium or other mental disorder. They are also usually accompanied by another cognitive dysfunction. For non-reversible causes of dementia such as age, the slow decline of memory and cognition is lifelong.
== Diagnostic Methods ==
There are multiple testing methods used to assess a patient's cognition and level of consciousness, including the Mini Mental Status Exam (MMSE), Montreal Cognitive Assessment (MoCA), Mini-Cog, and Cognitive Assessment Method (CAM), Glasgow Coma Score (GCS), Richmond Agitation and Sedation Scale (RASS), etc. The CAM has been shown to be the most commonly used tool to assess for delirium. Additionally, a meta-analysis looking at the accuracy and usefulness of the various testing methods reported that the MMSE was the most commonly used tool to evaluate major neurocognitive disorder, while the MoCA appeared to be the most useful when screening for minor neurocognitive disorder. More recent systematic reviews have demonstrated the need for further, well designed research on the Mini-Cog and MoCA for evaluating cognitive decline and the development of clinical guidelines on their use in various settings.
== Causes ==
=== Delirium ===
There are many causes of delirium, and many times there are multiple factors that can be contributing to delirium, particularly in the hospital setting. Common potential causes of delirium include new or worsening infections (i.e. urinary tract infections, pneumonia, and sepsis), neurological injury/infections (i.e. stroke and meningitis), environmental factors (i.e. immobilization and sleep deprivation), and medication/drug use (i.e. side effects of new medications, drug interactions, and use/withdrawal from recreational drugs).
=== Mild and major neurocognitive disorder ===
Neurocognitive disorders can have numerous causes: genetics, brain trauma, stroke, and heart issues. The main causes are neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease because they affect or deteriorate brain functions. Other diseases and conditions that cause NCDs include vascular dementia, frontotemporal degeneration, Lewy body disease, prion disease, normal pressure hydrocephalus, and dementia/neurocognitive issues due to HIV infection (AIDS). They may also include dementia due to substance abuse or exposure to toxins.
Neurocognitive disorders may also be caused by brain trauma, including concussions and traumatic brain injuries, as well as post-traumatic stress and alcoholism. This is referred to as amnesia, and is characterized by damage to major memory encoding parts of the brain such as the hippocampus. Difficulty creating recent term memories is called anterograde amnesia and is caused by damage to the hippocampus part of the brain, which is a major part of the memory process. Retrograde amnesia is also caused by damage to the hippocampus, but the memories that were encoded or in the process of being encoded in long-term memory are erased.
== Treatment ==
=== Delirium ===
The overarching principle of delirium treatment is finding and treating the underlying cause. If the patient is truly experiencing delirium, their symptoms should begin improving/resolving with proper treatment of their illness, intoxication, etc. Medication such as antipsychotics or benzodiazepines can help reduce the symptoms for some cases. For alcohol or malnourished cases, vitamin B supplements are recommended and for extreme cases, life-support can be used.
=== Mild and major neurocognitive disorder ===
There is no cure for neurocognitive disorder or the diseases that cause it. Antidepressants, antipsychotics, and other medications that help slow the progression of memory loss/behavioral symptoms are available and may help to treat the diseases. Ongoing psychotherapy and psychosocial support for patients and families are usually necessary for clear understanding and proper management of the disorder and to maintain a better quality of life for everyone involved; although older patients with major neurocognitive disorders usually require assistance with their daily activities leading to placement in long-term care homes. Speech therapy has been shown to help with language impairment, therefore improving long-term development and academic outcome.
Studies suggest that diets with high Omega 3 content, low in saturated fats and sugars, along with regular exercise can increase the level of brain plasticity. Other studies have shown that mental exercise such a newly developed "computerized brain training programs" can also help build and maintain targeted specific areas of the brain. These studies have been very successful for those diagnosed with schizophrenia and can improve fluid intelligence, the ability to adapt and deal with new problems or challenges the first time encountered, and in young people, it can still be effective in later life.
== See also ==
List of cognitive disorders
== References == | Wikipedia/Cognitive_dysfunction |
Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded receptor potentials. This process is called sensory transduction. The cell bodies of the sensory neurons are located in the dorsal root ganglia of the spinal cord.
The sensory information travels on the afferent nerve fibers in a sensory nerve, to the brain via the spinal cord. Spinal nerves transmit external sensations via sensory nerves to the brain through the spinal cord. The stimulus can come from exteroreceptors outside the body, for example those that detect light and sound, or from interoreceptors inside the body, for example those that are responsive to blood pressure or the sense of body position.
== Types and function ==
Sensory neurons in vertebrates are predominantly pseudounipolar or bipolar, and different types of sensory neurons have different sensory receptors that respond to different kinds of stimuli. There are at least six external and two internal sensory receptors:
=== External receptors ===
External receptors that respond to stimuli from outside the body are called exteroreceptors. Exteroreceptors include chemoreceptors such as olfactory receptors (smell) and taste receptors, photoreceptors (vision), thermoreceptors (temperature), nociceptors (pain), hair cells (hearing and balance), and a number of other different mechanoreceptors for touch and proprioception (stretch, distortion and stress).
==== Smell ====
The sensory neurons involved in smell are called olfactory sensory neurons. These neurons contain receptors, called olfactory receptors, that are activated by odor molecules in the air. The molecules in the air are detected by enlarged cilia and microvilli. These sensory neurons produce action potentials. Their axons form the olfactory nerve, and they synapse directly onto neurons in the cerebral cortex (olfactory bulb). They do not use the same route as other sensory systems, bypassing the brain stem and the thalamus. The neurons in the olfactory bulb that receive direct sensory nerve input, have connections to other parts of the olfactory system and many parts of the limbic system. 9.
==== Taste ====
Taste sensation is facilitated by specialized sensory neurons located in the taste buds of the tongue and other parts of the mouth and throat. These sensory neurons are responsible for detecting different taste qualities, such as sweet, sour, salty, bitter, and savory. When you eat or drink something, chemicals in the food or liquid interact with receptors on these sensory neurons, triggering signals that are sent to the brain. The brain then processes these signals and interprets them as specific taste sensations, allowing you to perceive and enjoy the flavors of the foods you consume. When taste receptor cells are stimulated by the binding of these chemical compounds (tastants), it can lead to changes in the flow of ions, such as sodium (Na+), calcium (Ca2+), and potassium (K+), across the cell membrane. In response to tastant binding, ion channels on the taste receptor cell membrane can open or close. This can lead to depolarization of the cell membrane, creating an electrical signal.
Similar to olfactory receptors, taste receptors (gustatory receptors) in taste buds interact with chemicals in food to produce an action potential.
==== Vision ====
Photoreceptor cells are capable of phototransduction, a process which converts light (electromagnetic radiation) into electrical signals. These signals are refined and controlled by the interactions with other types of neurons in the retina. The five basic classes of neurons within the retina are photoreceptor cells, bipolar cells, ganglion cells, horizontal cells, and amacrine cells. The basic circuitry of the retina incorporates a three-neuron chain consisting of the photoreceptor (either a rod or cone), bipolar cell, and the ganglion cell. The first action potential occurs in the retinal ganglion cell. This pathway is the most direct way for transmitting visual information to the brain. There are three primary types of photoreceptors: Cones are photoreceptors that respond significantly to color. In humans the three different types of cones correspond with a primary response to short wavelength (blue), medium wavelength (green), and long wavelength (yellow/red). Rods are photoreceptors that are very sensitive to the intensity of light, allowing for vision in dim lighting. The concentrations and ratio of rods to cones is strongly correlated with whether an animal is diurnal or nocturnal. In humans, rods outnumber cones by approximately 20:1, while in nocturnal animals, such as the tawny owl, the ratio is closer to 1000:1. Retinal ganglion cells are involved in the sympathetic response. Of the ~1.3 million ganglion cells present in the retina, 1-2% are believed to be photosensitive.
Issues and decay of sensory neurons associated with vision lead to disorders such as:
Macular degeneration – degeneration of the central visual field due to either cellular debris or blood vessels accumulating between the retina and the choroid, thereby disturbing and/or destroying the complex interplay of neurons that are present there.
Glaucoma – loss of retinal ganglion cells which causes some loss of vision to blindness.
Diabetic retinopathy – poor blood sugar control due to diabetes damages the tiny blood vessels in the retina.
==== Auditory ====
The auditory system is responsible for converting pressure waves generated by vibrating air molecules or sound into signals that can be interpreted by the brain.
This mechanoelectrical transduction is mediated with hair cells within the ear. Depending on the movement, the hair cell can either hyperpolarize or depolarize. When the movement is towards the tallest stereocilia, the Na+ cation channels open allowing Na+ to flow into cell and the resulting depolarization causes the Ca++ channels to open, thus releasing its neurotransmitter into the afferent auditory nerve. There are two types of hair cells: inner and outer. The inner hair cells are the sensory receptors .
Problems with sensory neurons associated with the auditory system leads to disorders such as:
Auditory processing disorder – Auditory information in the brain is processed in an abnormal way. Patients with auditory processing disorder can usually gain the information normally, but their brain cannot process it properly, leading to hearing disability.
Auditory verbal agnosia – Comprehension of speech is lost but hearing, speaking, reading, and writing ability is retained. This is caused by damage to the posterior superior temporal lobes, again not allowing the brain to process auditory input correctly.
==== Temperature ====
Thermoreceptors are sensory receptors, which respond to varying temperatures. While the mechanisms through which these receptors operate is unclear, recent discoveries have shown that mammals have at least two distinct types of thermoreceptors.
The bulboid corpuscle, is a cutaneous receptor a cold-sensitive receptor, that detects cold temperatures. The other type is a warmth-sensitive receptor.
==== Mechanoreceptors ====
Mechanoreceptors are sensory receptors which respond to mechanical forces, such as pressure or distortion.
Specialized sensory receptor cells called mechanoreceptors often encapsulate afferent fibers to help tune the afferent fibers to the different types of somatic stimulation. Mechanoreceptors also help lower thresholds for action potential generation in afferent fibers and thus make them more likely to fire in the presence of sensory stimulation.
Some types of mechanoreceptors fire action potentials when their membranes are physically stretched.
Proprioceptors are another type of mechanoreceptors which literally means "receptors for self". These receptors provide spatial information about limbs and other body parts.
Nociceptors are responsible for processing pain and temperature changes. The burning pain and irritation experienced after eating a chili pepper (due to its main ingredient, capsaicin), the cold sensation experienced after ingesting a chemical such as menthol or icillin, as well as the common sensation of pain are all a result of neurons with these receptors.
Problems with mechanoreceptors lead to disorders such as:
Neuropathic pain - a severe pain condition resulting from a damaged sensory nerve
Hyperalgesia - an increased sensitivity to pain caused by sensory ion channel, TRPM8, which is typically responds to temperatures between 23 and 26 degrees, and provides the cooling sensation associated with menthol and icillin
Phantom limb syndrome - a sensory system disorder where pain or movement is experienced in a limb that does not exist
=== Internal receptors ===
Internal receptors that respond to changes inside the body are known as interoceptors.
==== Blood ====
The aortic bodies and carotid bodies contain clusters of glomus cells – peripheral chemoreceptors that detect changes in chemical properties in the blood such as oxygen concentration. These receptors are polymodal responding to a number of different stimuli.
==== Nociceptors ====
Nociceptors respond to potentially damaging stimuli by sending signals to the spinal cord and brain. This process, called nociception, usually causes the perception of pain. They are found in internal organs as well as on the surface of the body to "detect and protect". Nociceptors detect different kinds of noxious stimuli indicating potential for damage, then initiate neural responses to withdraw from the stimulus.
Thermal nociceptors are activated by noxious heat or cold at various temperatures.
Mechanical nociceptors respond to excess pressure or mechanical deformation, such as a pinch.
Chemical nociceptors respond to a wide variety of chemicals, some of which signal a response. They are involved in the detection of some spices in food, such as the pungent ingredients in Brassica and Allium plants, which target the sensory neural receptor to produce acute pain and subsequent pain hypersensitivity.
== Connection with the central nervous system ==
Information coming from the sensory neurons in the head enters the central nervous system (CNS) through cranial nerves. Information from the sensory neurons below the head enters the spinal cord and passes towards the brain through the 31 spinal nerves. The sensory information traveling through the spinal cord follows well-defined pathways. The nervous system codes the differences among the sensations in terms of which cells are active.
== Classification ==
=== Adequate stimulus ===
A sensory receptor's adequate stimulus is the stimulus modality for which it possesses the adequate sensory transduction apparatus. Adequate stimulus can be used to classify sensory receptors:
Baroreceptors respond to pressure in blood vessels
Chemoreceptors respond to chemical stimuli
Electromagnetic radiation receptors respond to electromagnetic radiation
Infrared receptors respond to infrared radiation
Photoreceptors respond to visible light
Ultraviolet receptors respond to ultraviolet radiation
Electroreceptors respond to electric fields
Ampullae of Lorenzini respond to electric fields, salinity, and to temperature, but function primarily as electroreceptors
Hydroreceptors respond to changes in humidity
Magnetoreceptors respond to magnetic fields
Mechanoreceptors respond to mechanical stress or mechanical strain
Nociceptors respond to damage, or threat of damage, to body tissues, leading (often but not always) to pain perception
Osmoreceptors respond to the osmolarity of fluids (such as in the hypothalamus)
Proprioceptors provide the sense of position
Thermoreceptors respond to temperature, either heat, cold or both
=== Location ===
Sensory receptors can be classified by location:
Cutaneous receptors are sensory receptors found in the dermis or epidermis.
Muscle spindles contain mechanoreceptors that detect stretch in muscles.
=== Morphology ===
Somatic sensory receptors near the surface of the skin can usually be divided into two groups based on morphology:
Free nerve endings characterize the nociceptors and thermoreceptors and are called thus because the terminal branches of the neuron are unmyelinated and spread throughout the dermis and epidermis.
Encapsulated receptors consist of the remaining types of cutaneous receptors. Encapsulation exists for specialized functioning.
=== Rate of adaptation ===
A tonic receptor is a sensory receptor that adapts slowly to a stimulus and continues to produce action potentials over the duration of the stimulus. In this way it conveys information about the duration of the stimulus. Some tonic receptors are permanently active and indicate a background level. Examples of such tonic receptors are pain receptors, joint capsule, and muscle spindle.
A phasic receptor is a sensory receptor that adapts rapidly to a stimulus. The response of the cell diminishes very quickly and then stops. It does not provide information on the duration of the stimulus; instead some of them convey information on rapid changes in stimulus intensity and rate. An example of a phasic receptor is the Pacinian corpuscle.
== Drugs ==
There are many drugs currently on the market that are used to manipulate or treat sensory system disorders. For instance, gabapentin is a drug that is used to treat neuropathic pain by interacting with one of the voltage-dependent calcium channels present on non-receptive neurons. Some drugs may be used to combat other health problems, but can have unintended side effects on the sensory system. Dysfunction in the hair cell mechanotransduction complex, along with the potential loss of specialized ribbon synapses, can lead to hair cell death, often caused by ototoxic drugs like aminoglycoside antibiotics poisoning the cochlea. Through the use of these toxins, the K+ pumping hair cells cease their function. Thus, the energy generated by the endocochlear potential which drives the auditory signal transduction process is lost, leading to hearing loss.
== Neuroplasticity ==
Ever since scientists observed cortical remapping in the brain of Taub's Silver Spring monkeys, there has been a large amount of research into sensory system plasticity. Huge strides have been made in treating disorders of the sensory system. Techniques such as constraint-induced movement therapy developed by Taub have helped patients with paralyzed limbs regain use of their limbs by forcing the sensory system to grow new neural pathways. Phantom limb syndrome is a sensory system disorder in which amputees perceive that their amputated limb still exists and they may still be experiencing pain in it. The mirror box developed by V.S. Ramachandran, has enabled patients with phantom limb syndrome to relieve the perception of paralyzed or painful phantom limbs. It is a simple device which uses a mirror in a box to create an illusion in which the sensory system perceives that it is seeing two hands instead of one, therefore allowing the sensory system to control the "phantom limb". By doing this, the sensory system can gradually get acclimated to the amputated limb, and thus alleviate this syndrome.
== Other animals ==
Hydrodynamic reception is a form of mechanoreception used in a range of animal species.
== Additional images ==
== See also ==
Pseudounipolar neuron
Neural coding
Posterior column
Receptive field
Sensory system
List of distinct cell types in the adult human body
Sensory nerve
Motor nerve
Afferent nerve fiber
Efferent nerve fiber
Motor neuron
== References ==
== External links ==
Media related to Sensory neuron at Wikimedia Commons
Purves D, Augustine GJ, Fitzpatrick D, et al., eds. (2001). "Table 9.1 The major classes of somatic sensory receptors". Neuroscience (2nd ed.). Sunderland MA: Sinauer Associates. ISBN 0-87893-742-0. | Wikipedia/Sensory_neurons |
Neuronal galvanotropism is the ability to direct the outgrowth of neuronal processes through the use of an extracellular electric field. This technique has been researched since the late 1920s and has been shown to direct the formation of both axonic and dendritic processes in cell culture. It is only possible to direct outgrowth of in vitro preparations at this point. In vitro preparations involve the use of a culture dish, in which there is a species-specific neuronal growth factor. Neurons are removed from a chosen animal, plated onto the dish and allowed to grow (often kept in incubation). The application of an extracellular electric field shows that the cells will grow processes in a direction that demonstrates the direction of the applied electric field. This could be either in the direction of the cathode or anode, depending on the type of substrate the cells are plated onto.
The mechanism underlying this behavior is thought to involve the effect of the electric field on receptors and membrane proteins on the cell's surface. These charged proteins would experience an electrophoretic force pulling them toward the oppositely charged pole of the electric field. Most of these membrane proteins are negatively charged, but the growth, when observed appears to be directed to the negative pole (cathode). This is a strange behavior that can only be accounted for by electroosmotic effects. Positively charged ions outside the cell experience a force towards the cathode. There is a flux of these ions outside the cell and the shear force of solution movement is thought to pull the neurite in the cathodal direction. Also, the electric field may depolarize the cell near the cathodal side opening voltage-gated calcium channels and allowing calcium ions to enter the cell. Calcium is widely believed to be a factor in neurite outgrowth. This theory has been challenged in a recent paper by scientists at Purdue University. Recent studies also involve differentiating between the effect of current on growth direction and the effect of a simple electric field. Studies involving AC and DC fields are also being conducted.
This is currently a highly researched topic, in which many neuroscience labs around the world are attempting to be the first to have a feasible method of directing outgrowth. Potential applications involve the direction and regeneration of severed nerves although these would only become available in the very distant future. This technique would also be useful in the study of neuronal networks. Neurites could be directed toward each other over large distances and allowed to form synapses. Networks of hundreds or thousands of cells could be constructed and studied.
== References == | Wikipedia/Neuronal_galvanotropism |
A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junctions, or skeletal muscles, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and weakness. Issues with sensation can also occur.
Neuromuscular diseases can be acquired or genetic. Mutations of more than 650 genes have shown to be causes of neuromuscular diseases. Other causes include nerve or muscle degeneration, autoimmunity, toxins, medications, malnutrition, metabolic derangements, hormone imbalances, infection, nerve compression/entrapment, comprised blood supply, and trauma.
== Signs and symptoms ==
Symptoms of neuromuscular disease may include numbness, paresthesia, muscle atrophy, a pseudoathletic appearance, exercise intolerance, myalgia (muscle pain), fasciculations (muscle twitches), myotonia (delayed muscle relaxation), hypotonia (lack of resistance to passive movement), fixed muscle weakness (a static symptom), or premature muscle fatigue (a dynamic symptom).
== Causes ==
Neuromuscular disease can be caused by autoimmune disorders, genetic/hereditary disorders and some forms of the collagen disorder Ehlers–Danlos syndrome, exposure to environmental chemicals and poisoning which includes heavy metal poisoning. The failure of the electrical insulation surrounding nerves, the myelin, is seen in certain deficiency diseases, such as the failure of the body's system for absorbing vitamin B-12.
Diseases of the motor end plate include myasthenia gravis, a form of muscle weakness due to antibodies against acetylcholine receptor, and its related condition Lambert–Eaton myasthenic syndrome (LEMS). Tetanus and botulism are bacterial infections in which bacterial toxins cause increased or decreased muscle tone, respectively. Muscular dystrophies, including Duchenne's and Becker's, are a large group of diseases, many of them hereditary or resulting from genetic mutations, where the muscle integrity is disrupted, they lead to progressive loss of strength and decreased life span.
Further causes of neuromuscular diseases are:
Inflammatory muscle disorders
Polymyalgia rheumatica (or "muscle rheumatism") is an inflammatory condition that mainly occurs in the elderly; it is associated with giant-cell arteritis (It often responds to prednisolone).
Polymyositis is an autoimmune condition in which the muscle is affected.
Rhabdomyolysis is the breakdown of muscular tissue due to any cause.
Tumors
Smooth muscle: leiomyoma (benign)
Striated muscle: rhabdomyoma (benign)
== Diagnosis ==
Diagnostic procedures that may reveal muscular disorders include direct clinical observations. This usually starts with the observation of bulk, possible atrophy or loss of muscle tone. Neuromuscular disease can also be diagnosed by various blood tests and using electrodiagnostic medicine tests including electromyography (measuring electrical activity in muscles) and nerve conduction studies. Genetic testing is an important part of diagnosing inherited neuromuscular conditions.
== Prognosis ==
Prognosis and management vary by disease.
== See also ==
List of neuromuscular disorders
Motor neuron diseases
Neuromuscular medicine
== Notes ==
== References ==
== Further reading ==
Wokke, John H. J.; Doorn, Pieter A. van; Hoogendijk, Jessica E.; Visser, Marianne de (2013-03-07). Neuromuscular Disease: A Case-Based Approach. Cambridge University Press. ISBN 9781107328044.
Ambrosino, N; Carpene, N; Gherardi, M (2009). "Chronic respiratory care for neuromuscular diseases in adults". European Respiratory Journal. 34 (2): 444–451. doi:10.1183/09031936.00182208. PMID 19648521.
== External links == | Wikipedia/Neuromuscular_disease |
Charcot-Marie-Tooth disease (CMT) is an inherited neurological disorder that affects the peripheral nerves responsible for transmitting signals between the brain, spinal cord, and the rest of the body.
This is the most common inherited neuropathy that causes sensory and motor symptoms of numbness, tingling, weakness and muscle atrophy, pain, and progressive foot deformities over time. In some cases, CMT also affects nerves controlling automatic bodily functions like sweating and balance. Symptoms typically start in the feet and legs before spreading to the hands and arms. While some individuals experience minimal symptoms, others may face significant physical limitations. There is no cure for CMT; however, treatments such as physical therapy, orthopedic devices, surgery, and medications can help manage symptoms and improve quality of life.
CMT is caused by mutations in over 100 different genes, which disrupt the function of nerve cells' axons (responsible for transmitting signals) and their myelin sheaths (which insulate and accelerate signal transmission). When these components are damaged, nerve signal transmission slows down or becomes impaired, leading to problems with muscle control and sensory feedback. The condition was discovered in 1886 by Doctors Jean-Martin Charcot and Pierre Marie of France and Howard Henry Tooth of the United Kingdom.
This disease is the most commonly inherited neurological disorder, affecting approximately one in 2,500 people.
== Signs and symptoms ==
The symptoms of CMT often appear in childhood and adolescence, but in some cases, they may not develop until adulthood. The severity and progression of symptoms can vary widely between individuals even among members of the same family. Some people do not experience symptoms until their early 30s or 40s. The most common early sign of CMT is difficulty walking, often due to weakness in the muscles of the lower legs and feet. This muscle weakness can lead to foot drop, where patients have trouble lifting the front part of the foot, causing them to trip or adopt a high-stepping gait. Over time, individuals may develop distinctive foot deformities, such as high arches (known as pes cavus) and curled toes (hammertoes), due to muscle imbalance.
As the disease progresses, the weakness often spreads to the hands and forearms, making tasks that require fine motor skills—like buttoning a shirt or writing—more difficult. In addition to motor symptoms, many people with CMT also experience a gradual loss of sensation in the feet, legs, hands, and arms. This sensory loss may affect the ability to feel pain, temperature, or touch, and can lead to problems with balance, especially in low-light conditions.
Symptoms and progression of the disease can vary. Involuntary grinding of teeth and squinting are prevalent and often go unnoticed by the person affected. Breathing can be affected in some, as can hearing, vision, and neck and shoulder muscles. Scoliosis is common, causing hunching and loss of height. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT, as can difficulty chewing, swallowing, and speaking (due to atrophy of vocal cords). A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as severe emotional stress. Patients with CMT must avoid periods of prolonged immobility, such as when recovering from a secondary injury, as prolonged periods of limited mobility can drastically accelerate symptoms of CMT.
Pain is a common symptom experienced by individuals with Charcot-Marie-Tooth disease, often resulting from postural abnormalities, skeletal deformities, muscle fatigue, and cramping. This pain can typically be managed through a combination of physical therapy, orthopedic interventions, and the use of corrective or assistive devices. In cases where these approaches do not provide sufficient relief, analgesic medications may be necessary to alleviate discomfort and improve quality of life.
Although the disease is typically slowly progressive and not life-threatening, the degree of disability can vary. Some people may live relatively normal lives with mild symptoms, while others may require orthopedic supports, physical therapy, or even surgery to manage complications.
The variation in symptoms and severity is influenced by the specific genetic mutation causing the condition. While some genes are linked to earlier onset and more severe forms of CMT, others result in milder forms with slower progression. Furthermore, even when the same gene is involved, the symptoms can differ between individuals.
Neuropathic pain is a recognized symptom of Charcot-Marie-Tooth disease, although its presence and severity can vary greatly among individuals, and not all patients experience pain. For some, it can be moderate to severe and significantly interfere with daily activities and overall quality of life. When it presents, the pain experienced in CMT is often similar in character to that observed in other forms of peripheral neuropathy, including postherpetic neuralgia and complex regional pain syndrome. Addressing this symptom typically requires an individualized treatment plan, which may include pharmacological interventions, physical therapy, and other supportive strategies to manage and alleviate discomfort.
Charcot-Marie-Tooth disease type 1A (CMT1A) can also include mild enlargement or hypertrophy of leg muscles, particularly the calves, alongside typical symptoms of distal muscle weakness and atrophy. However, this muscle enlargement typically represents pseudohypertrophy due to fatty tissue infiltration rather than actual muscle growth.
This hypertrophic type of CMT is not caused by the muscles enlarging directly, but by pseudohypertrophy of the legs as fatty tissue enters the leg muscles.
== Causes and Genetics ==
Charcot-Marie-Tooth (CMT) disease is an inherited neurological disorder primarily caused by genetic mutations that disrupt critical proteins within peripheral nerves. These mutations predominantly affect proteins essential for the structure and function of the myelin sheath, including peripheral myelin protein 22 (PMP22), myelin protein zero (P0/MPZ), connexin32 (Cx32/GJB1), and periaxin (PRX), leading to demyelination. Additionally, mutations in proteins involved in axonal integrity, such as neurofilament light chain (NF-L), dynamin 2 (DNM2), ganglioside-induced differentiation-associated protein 1 (GDAP1), and mitofusin 2 (MFN2), can cause axonal forms of CMT. Due to the close interaction between Schwann cells (which produce myelin) and axons, mutations affecting Schwann cells often result in secondary axonal degeneration, further complicating disease progression. Ultimately, the pathogenesis of CMT involves the disruption of essential cellular processes, including protein synthesis, sorting, intracellular transport, protein degradation, and mitochondrial function, highlighting the complex molecular mechanisms underlying this disorder.
In some forms like X-linked CMT (CMTX), mutations in the GJB1 gene lead to dysfunction in gap junctions within Schwann cells, further impairing nerve signal transmission.
== Classification ==
Charcot–Marie–Tooth (CMT) disease is a genetically heterogeneous disorder, meaning that it can be caused by mutations in many different genes.
To date, dozens of genes have been linked to various forms of CMT, reflecting the complexity of its molecular basis. As a result, CMT is classified into several major types, such as CMT1, CMT2, CMT4, CMTX, and intermediate forms, based on the pattern of inheritance and whether the primary defect affects the myelin sheath or the axon. CMT1 involves demyelination and is most caused by duplication of the PMP22 gene, while CMT2 is primarily axonal and frequently linked to mutations in genes such as MFN2 or NEFL. X-linked and autosomal recessive forms, like CMTX and CMT4, are also recognized and often associated with more severe or early-onset symptoms.
Each type is further divided into subtypes, defined by the specific gene that is mutated. This genetic classification helps guide diagnosis, prognosis, and, potentially, the development of targeted therapies
=== GARS1-related axonal neuropathy (CMT2) ===
Charcot–Marie–Tooth type 2 (CMT2) is commonly classified as an axonal neuropathy due to the degeneration of nerve axons observed in affected individuals. Unlike CMT type 1, which results from damage to the myelin sheath, CMT type 2 is characterized by direct injury to the axon itself.. This axonal damage can disrupt nerve signal transmission between the brain and muscles, resulting in symptoms such as muscle weakness, atrophy, reduced sensation, and foot deformities. The onset of symptoms in CMT2 typically occurs between the ages of 5 and 25.
CMT2D is one of more than 31 recognized subtypes of Charcot–Marie–Tooth disease type 2 (CMT2) and is diagnosed when both motor and sensory deficits are present—such as loss of sensation caused by degeneration of sensory axons. In cases where only motor symptoms are observed without sensory involvement, the condition is classified as distal hereditary motor neuropathy type V (dHMN-V). The reason behind the variability in sensory involvement among patients with GARS1-related neuropathy remains unclear.
Symptoms of CMT2D typically include muscle weakness, loss of sensation, reduced reflexes, and muscle atrophy, which are similar to those seen in both CMT1 and other CMT2 variants. The severity and combination of symptoms vary widely among patients, particularly regarding the extent of sensory involvement.
CMT2D is a result of autosomal dominant mutations in the human GARS1 gene located at 7p14.3 and is thought to be caused by aberrant gain-of-function missense mutations.
The GARS1 gene encodes the enzyme glycyl-tRNA synthetase (GlyRS), which belongs to the class II group of aminoacyl-tRNA synthetases. This enzyme is essential in the process of protein synthesis, facilitating the bonding of the amino acid glycine to its corresponding transfer RNA (tRNA). Through this process, GlyRS ensures the accurate incorporation of glycine during translation, making it essential for proper protein production.
Many different mutations have been found in CMT2D patients, and how mutations in GARS1 cause CMT2D remains unclear. However, mutant glycyl-tRNA synthetase (GlyRS) is thought to interfere with transmembrane receptors, causing motor disease, and that mutations in the gene could disrupt the ability of GlyRS to interact with its cognate RNA, disrupting protein production. The GARS1 mutations present in CMT2D cause a deficient amount of glycyl-tRNA in cells, preventing the elongation phase of protein synthesis. Elongation is a key step in protein production, so when a deficiency of glycyl-tRNA exists, protein synthesis is unable to continue at glycine sites. GARS1 mutations also stall initiation of translation due to a stress response that is induced by glycine addition failure. By stalling elongation and initiation of translation, CMT2D mutations in GARS1 cause translational repression, meaning that overall translation is inhibited.
GARS1-associated axonal neuropathy is a progressive condition that deteriorates over time. Although the precise mechanisms driving the chronic neurodegeneration caused by mutant glycyl-tRNA synthetase (GlyRS) remain unclear, one proposed theory involves disrupted vascular endothelial growth factor (VEGF) signaling. The mutant GlyRS aberrantly interacts with neuronal transmembrane receptors, such as neuropilin 1 (Nrp1) and VEGF receptors, interfering with normal signaling pathways and contributing to the development of neuropathy.
GARS-CMT2D mutations alter GlyRS and allow it to bind to the Nrp1 receptor, interfering with the normal binding of Nrp1 to VEGF. While enhanced expression of VEGF improves motor function, reduced expression of Nrp1 worsens CMT2D; because Nrp1 binds to mutant GlyRS in mutant GARS1-CMT2D individuals, Nrp1 expression is reduced, in turn worsening motor function. Mice with deficient VEGF demonstrate motor neuron disease over time. Thus, the VEGF/Nrp1 pathway is considered to be targetable for CMT2D treatment.
=== X-linked CMT ===
Main article: X-linked Charcot–Marie–Tooth disease
CMT can also be produced by X-linked mutations, in which case it is called X-linked CMT (CMTX). In CMTX, mutated connexons create nonfunctional gap junctions that interrupt molecular exchange and signal transport.The mutation can appear in the GJB1 gene coding for the connexin 32 protein, a gap junction protein expressed in Schwann cells. Because this protein is also present in oligodendrocytes, demyelination can appear in the CNS as well.
Schwann cells create the myelin sheath by wrapping their plasma membranes around the axon. These Schwann cells work together with neurons and fibroblasts to create a functional nerve. Schwann cells and neurons exchange molecular signals by way of gap junctions that regulate survival and differentiation.
Demyelinating Schwann cells cause abnormal axon structure and function. They may cause axon degeneration, or they may simply cause axons to malfunction. The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, however, nerve signals are slower. This can be measured by a common neurological test, electromyography. When the axon is damaged, the result is a reduced compound muscle action potential.
== Diagnosis ==
Charcot–Marie–Tooth (CMT) disease can be diagnosed using a combination of three primary methods: nerve conduction studies, nerve biopsy, and genetic testing. Nerve conduction studies assess the velocity of electrical impulses traveling through nerves, whereas nerve biopsy entails the examination of small samples of nerve tissue. Genetic testing can conclusively diagnose CMT by identifying specific mutations linked to the condition. however, but not all the genetic markers for CMT are known. Initial signs of CMT often include lower leg weakness, such as foot drop, and foot deformities like high arches or hammertoes. However, these symptoms alone do not provide enough information for a diagnosis. Individuals showing signs of CMT should be referred to a neurologist or rehabilitation medicine specialist for further evaluation and treatment.During a physical examination, the physician may assess muscle strength such as asking the patient to walk on their heels or resist applied pressure on their legs and check for sensory loss and reduced deep-tendon reflexes, such as the knee-jerk response. A detailed family history is also important, as CMT is an inherited condition. While the absence of a family history does not rule out CMT, it can help the physician distinguish it from other causes of neuropathy, such as diabetes, toxin exposure, or certain medications.
== Treatment and Management ==
There is no cure for CMT, but its symptoms can be managed to maintain quality of life. Physical and occupational therapy can help preserve muscle strength, flexibility, and mobility
Orthopedic devices like ankle-foot orthoses (AFOs) are commonly used to correct foot drop and improve gait. In some cases, surgical interventions may be necessary to straighten toes, lower arches, or fuse joints to enhance stability. Pain management may involve physical therapy, assistive devices, or medications for neuropathic pain. Patients are advised to avoid prolonged immobility, which can accelerate disease progression. Certain drugs, such as vincristine (a chemotherapy agent), should be avoided altogether in CMT patients due to their known toxicity to nerves. Regular follow-up with healthcare providers is essential to adapt care as the disease progresses.
== History ==
Charcot-Marie-Tooth disease was first discovered in 1886 by three scientists: the Jean-Martin Charcot (1825–1893), and his assistant Pierre Marie (1853–1940), along with the English doctor Howard Henry Tooth (1856–1925). In their original publication, titled “Concerning a Special Form of Progressive Muscular Atrophy,” Charcot and Marie acknowledged that similar cases had been previously published in medical literature
Their findings described hereditary neuropathy, marked by gradual muscle wasting and diminished sensation in the extremities.This crucial discovery helped establish CMT as a distinct clinical entity, differentiating it from other neuromuscular conditions such as muscular dystrophies. Over the years, advancements in neurogenetics have led to the identification of various genetic mutations responsible for the disease, significantly enhancing our understanding of its pathogenesis and classification.
Charcot also noted that prior descriptions of the disease were neither objective nor thorough. Most of the earlier accounts merely mentioned that CMT was hereditary. As a result, Charcot felt it was essential to provide a comprehensive description of the disease, ensuring that it received the attention it deserved.
In 2010, Charcot–Marie–Tooth (CMT) disease became one of the first conditions in which the precise genetic cause was identified in an individual patient using whole-genome sequencing. This groundbreaking discovery was made by scientists affiliated with the Charcot–Marie–Tooth Association (CMTA). The analysis revealed two mutations in the SH3TC2 gene, which is already known to be associated with CMT. To better understand the inheritance pattern, researchers compared the genome of the affected individual with those of the patient's parents and seven siblings—some of whom had the disease and others who did not. Both parents were found to carry one normal and one mutated copy of the SH3TC2 gene and showed either mild or no symptoms. However, children who inherited two mutated copies of the gene exhibited the full clinical features of the disease.
== See also ==
Charcot–Marie–Tooth disease classifications
Palmoplantar keratoderma and spastic paraplegia
Hereditary motor and sensory neuropathies
Hereditary motor neuropathies
Low copy repeats
Christina's World
== References ==
== External links ==
Media related to Charcot-Marie-Tooth disease at Wikimedia Commons | Wikipedia/Charcot–Marie–Tooth_disease |
Alpha (α) motor neurons (also called alpha motoneurons), are large, multipolar lower motor neurons of the brainstem and spinal cord. They innervate extrafusal muscle fibers of skeletal muscle and are directly responsible for initiating their contraction. Alpha motor neurons are distinct from gamma motor neurons, which innervate intrafusal muscle fibers of muscle spindles.
While their cell bodies are found in the central nervous system (CNS), α motor neurons are also considered part of the somatic nervous system—a branch of the peripheral nervous system (PNS)—because their axons extend into the periphery to innervate skeletal muscles.
An alpha motor neuron and the muscle fibers it innervates comprise a motor unit. A motor neuron pool contains the cell bodies of all the alpha motor neurons involved in contracting a single muscle.
== Location ==
Alpha motor neurons (α-MNs) innervating the head and neck are found in the brainstem; the remaining α-MNs innervate the rest of the body and are found in the spinal cord. There are more α-MNs in the spinal cord than in the brainstem, as the number of α-MNs is directly proportional to the amount of fine motor control in that muscle. For example, the muscles of a single finger have more α-MNs per fibre, and more α-MNs in total, than the muscles of the quadriceps, which allows for finer control of the force a finger applies.
In general, α-MNs on one side of the brainstem or spinal cord innervate muscles on that same side of the body. An exception is the trochlear nucleus in the brainstem, which innervates the superior oblique muscle of the eye on the opposite side of the face.
=== Brainstem ===
In the brainstem, α-MNs and other neurons reside within clusters of cells called nuclei, some of which contain the cell bodies of neurons belonging to the cranial nerves. Not all cranial nerve nuclei contain α-MNs; those that do are motor nuclei, while others are sensory nuclei. Motor nuclei are found throughout the brainstem—medulla, pons, and midbrain—and for developmental reasons are found near the midline of the brainstem.
Generally, motor nuclei found higher in the brainstem (i.e., more rostral) innervate muscles that are higher on the face. For example, the oculomotor nucleus contains α-MNs that innervate muscles of the eye, and is found in the midbrain, the most rostral brainstem component. By contrast, the hypoglossal nucleus, which contains α-MNs that innervate the tongue, is found in the medulla, the most caudal (i.e., towards the bottom) of the brainstem structures.
=== Spinal cord ===
In the spinal cord, α-MNs are located within the gray matter that forms the ventral horn. These α-MNs provide the motor component of the spinal nerves that innervate muscles of the body.
As in the brainstem, higher segments of the spinal cord contain α-MNs that innervate muscles higher on the body. For example, the biceps brachii muscle, a muscle of the arm, is innervated by α-MNs in spinal cord segments C5, C6, and C7, which are found rostrally in the spinal cord. On the other hand, the gastrocnemius muscle, one of the muscles of the leg, is innervated by α-MNs within segments S1 and S2, which are found caudally in the spinal cord.
Alpha motor neurons are located in a specific region of the spinal cord's gray matter. This region is designated lamina IX in the Rexed lamina system, which classifies regions of gray matter based on their cytoarchitecture. Lamina IX is located predominantly in the medial aspect of the ventral horn, although there is some contribution to lamina IX from a collection of motor neurons located more laterally. Like other regions of the spinal cord, cells in this lamina are somatotopically organized, meaning that the position of neurons within the spinal cord is associated with what muscles they innervate. In particular, α-MNs in the medial zone of lamina IX tend to innervate proximal muscles of the body, while those in the lateral zone tend to innervate more distal muscles. There is similar somatotopy associated with α-MNs that innervate flexor and extensor muscles: α-MNs that innervate flexors tend to be located in the dorsal portion of lamina IX; those that innervate extensors tend to be located more ventrally.
== Development ==
Alpha motor neurons originate in the basal plate, the ventral portion of the neural tube in the developing embryo. Sonic hedgehog (Shh) is secreted by the nearby notochord and other ventral structures (e.g., the floor plate), establishing a gradient of highly concentrated Shh in the basal plate and less concentrated Shh in the alar plate. Under the influence of Shh and other factors, some neurons of the basal plate differentiate into α-MNs.
Like other neurons, α-MNs send axonal projections to reach their target extrafusal muscle fibers via axon guidance, a process regulated in part by neurotrophic factors released by target muscle fibers. Neurotrophic factors also ensure that each muscle fiber is innervated by the appropriate number of α-MNs. As with most types of neurons in the nervous system, α-MNs are more numerous in early development than in adulthood. Muscle fibers secrete a limited amount of neurotrophic factors capable of sustaining only a fraction of the α-MNs that initially project to the muscle fiber. Those α-MNs that do not receive sufficient neurotrophic factors will undergo apoptosis, a form of programmed cell death.
Because they innervate many muscles, some clusters of α-MNs receive high concentrations of neurotrophic factors and survive this stage of neuronal pruning. This is true of the α-MNs innervating the upper and lower limbs: these α-MNs form large cell columns that contribute to the cervical and lumbar enlargements of the spinal cord. In addition to receiving neurotrophic factors from muscles, α-MNs also secrete a number of trophic factors to support the muscle fibers they innervate. Reduced levels of trophic factors contributes to the muscle atrophy that follows an α-MN lesion.
== Connectivity ==
Like other neurons, lower motor neurons have both afferent (incoming) and efferent (outgoing) connections. Alpha motor neurons receive input from a number of sources, including upper motor neurons, sensory neurons, and interneurons. The primary output of α-MNs is to extrafusal muscle fibers. This afferent and efferent connectivity is required to achieve coordinated muscle activity.
=== Afferent input ===
Upper motor neurons (UMNs) send input to α-MNs via several pathways, including (but not limited to) the corticonuclear, corticospinal, and rubrospinal tracts. The corticonuclear and corticospinal tracts are commonly encountered in studies of upper and lower motor neuron connectivity in the control of voluntary movements.
The corticonuclear tract is so named because it connects the cerebral cortex to cranial nerve nuclei. (The corticonuclear tract is also called the corticobulbar tract, as the target in the brainstem—which is medulla—is archaically called the "bulb.") It is via this pathway that upper motor neurons descend from the cortex and synapse on α-MNs of the brainstem. Similarly, UMNs of the cerebral cortex are in direct control of α-MNs of the spinal cord via the lateral and ventral corticospinal tracts.
The sensory input to α-MNs is extensive and has its origin in Golgi tendon organs, muscle spindles, mechanoreceptors, thermoreceptors, and other sensory neurons in the periphery. These connections provide the structure for the neural circuits that underlie reflexes. There are several types of reflex circuits, the simplest of which consists of a single synapse between a sensory neuron and a α-MNs. The knee-jerk reflex is an example of such a monosynaptic reflex.
The most extensive input to α-MNs is from local interneurons, which are the most numerous type of neuron in the spinal cord. Among their many roles, interneurons synapse on α-MNs to create more complex reflex circuitry. One type of interneuron is the Renshaw cell.
=== Efferent output ===
Alpha motor neurons send fibers that mainly synapse on extrafusal muscle fibers. Other fibers from α-MNs synapse on Renshaw cells, i.e. inhibitory interneurons that synapse on the α-MN and limit its activity in order to prevent muscle damage.
== Signaling ==
Like other neurons, α-MNs transmit signals as action potentials, rapid changes in electrical activity that propagate from the cell body to the end of the axon. To increase the speed at which action potentials travel, α-MN axons have large diameters and are heavily myelinated by both oligodendrocytes and Schwann cells. Oligodendrocytes myelinate the part of the α-MN axon that lies in the central nervous system (CNS), while Schwann cells myelinate the part that lies in the peripheral nervous system (PNS). The transition between the CNS and PNS occurs at the level of the pia mater, the innermost and most delicate layer of meningeal tissue surrounding components of the CNS.
The axon of an α-MN connects with its extrafusal muscle fiber via a neuromuscular junction, a specialized type of chemical synapse that differs both in structure and function from the chemical synapses that connect neurons to each other. Both types of synapses rely on neurotransmitters to transduce the electrical signal into a chemical signal and back. One way they differ is that synapses between neurons typically use glutamate or GABA as their neurotransmitters, while the neuromuscular junction uses acetylcholine exclusively. Acetylcholine is sensed by nicotinic acetylcholine receptors on extrafusal muscle fibers, causing their contraction.
Like other motor neurons, α-MNs are named after the properties of their axons. Alpha motor neurons have Aα axons, which are large-caliber, heavily myelinated fibers that conduct action potentials rapidly. By contrast, gamma motor neurons have Aγ axons, which are slender, lightly myelinated fibers that conduct less rapidly.
== Clinical significance ==
Injury to α-MNs is the most common type of lower motor neuron lesion. Damage may be caused by trauma, ischemia, and infection, among others. In addition, certain diseases are associated with the selective loss of α-MNs. For example, poliomyelitis is caused by a virus that specifically targets and kills motor neurons in the ventral horn of the spinal cord. Amyotropic lateral sclerosis likewise is associated with the selective loss of motor neurons.
Paralysis is one of the most pronounced effects of damage to α-MNs. Because α-MNs provide the only innervation to extrafusal muscle fibers, losing α-MNs effectively severs the connection between the brainstem and spinal cord and the muscles they innervate. Without this connection, voluntary and involuntary (reflex) muscle control is impossible. Voluntary muscle control is lost because α-MNs relay voluntary signals from upper motor neurons to muscle fibers. Loss of involuntary control results from interruption of reflex circuits such as the tonic stretch reflex. A consequence of reflex interruption is that muscle tone is reduced, resulting in flaccid paresis. Another consequence is the depression of deep tendon reflexes, causing hyporeflexia.
Muscle weakness and atrophy are inevitable consequences of α-MN lesions as well. Because muscle size and strength are related to the extent of their use, denervated muscles are prone to atrophy. A secondary cause of muscle atrophy is that denervated muscles are no longer supplied with trophic factors from the α-MNs that innervate them. Alpha motor neuron lesions also result in abnormal EMG potentials (e.g., fibrillation potentials) and fasciculations, the latter being spontaneous, involuntary muscle contractions.
Diseases that impair signaling between α-MNs and extrafusal muscle fibers, namely diseases of the neuromuscular junction have similar signs to those that occur with α-MN disease. For example, myasthenia gravis is an autoimmune disease that prevents signaling across the neuromuscular junction, which results in functional denervation of muscle.
== See also ==
Beta motor neuron
Anterior grey column
== References ==
== External links ==
NIF Search - Alpha Motor Neuron Archived 2016-03-04 at the Wayback Machine via the Neuroscience Information Framework | Wikipedia/Alpha_motor_neuron |
An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system.
== Structure ==
Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are bipolar neurons with dendrites facing the external surface of the cribriform plate with axons that pass through the cribriform foramina with terminal end at olfactory bulbs. The ORNs are located in the olfactory epithelium in the nasal cavity. The cell bodies of the ORNs are distributed among the stratified layers of the olfactory epithelium.
Many tiny hair-like non-motile cilia protrude from the olfactory receptor cell's dendrites. The dendrites extend to the olfactory epithelial surface and each ends in a dendritic knob from which around 20 to 35 cilia protrude. The cilia have a length of up to 100 micrometres and with the cilia from other dendrites form a meshwork in the olfactory mucus. The surface of the cilia is covered with olfactory receptors, a type of G protein-coupled receptor. Each olfactory receptor cell expresses only one type of olfactory receptor (OR), but many separate olfactory receptor cells express ORs which bind the same set of odors. The axons of olfactory receptor cells which express the same OR converge to form glomeruli in the olfactory bulb.
== Function ==
ORs, which are located on the membranes of the cilia have been classified as a complex type of ligand-gated metabotropic channels. There are approximately 1000 different genes that code for the ORs, making them the largest gene family. An odorant will dissolve into the mucus of the olfactory epithelium and then bind to an OR. ORs can bind to a variety of odor molecules, with varying affinities. The difference in affinities causes differences in activation patterns resulting in unique odorant profiles. The activated OR in turn activates the intracellular G-protein, GOLF (GNAL), adenylate cyclase and production of cyclic AMP (cAMP) opens ion channels in the cell membrane, resulting in an influx of sodium and calcium ions into the cell, and an efflux of chloride ions. This influx of positive ions and efflux of negative ions causes the neuron to depolarize, generating an action potential.
=== Desensitization ===
The olfactory receptor neuron has a fast working negative feedback response upon depolarization. When the neuron is depolarizing, the CNG ion channel is open allowing sodium and calcium to rush into the cell. The influx of calcium begins a cascade of events within the cell. Calcium first binds to calmodulin to form CaM. CaM will then bind to the CNG channel and close it, stopping the sodium and calcium influx. CaMKII will be activated by the presence of CaM, which will phosphorylate ACIII and reduce cAMP production. CaMKII will also activate phosphodiesterase, which will then hydrolyze cAMP. The effect of this negative feedback response inhibits the neuron from further activation when another odor molecule is introduced.
=== Number of distinguishable odors ===
A widely publicized study suggested that humans can detect more than one trillion different odors. This finding has been disputed. Critics argued that the methodology used for the estimation was fundamentally flawed, showing that applying the same argument for better-understood sensory modalities, such as vision or audition, leads to wrong conclusions. Other researchers have also showed that the result is extremely sensitive to the precise details of the calculation, with small variations changing the result over dozens of orders of magnitude, possibly going as low as a few thousand. The authors of the original study have argued that their estimate holds as long as it is assumed that odor space is sufficiently high-dimensional.
== Other animals ==
== See also ==
Chemoreceptor
Sensory receptor
List of distinct cell types in the adult human body
== References ==
== External links ==
Insect olfaction | Wikipedia/Olfactory_receptor_neuron |
Interneurons (also called internuncial neurons, association neurons, connector neurons, or intermediate neurons) are neurons that are not specifically motor neurons or sensory neurons. Interneurons are the central nodes of neural circuits, enabling communication between sensory or motor neurons and the central nervous system (CNS). They play vital roles in reflexes, neuronal oscillations, and neurogenesis in the adult mammalian brain.
Interneurons can be further broken down into two groups: local interneurons and relay interneurons. Local interneurons have short axons and form circuits with nearby neurons to analyze small pieces of information. Relay interneurons have long axons and connect circuits of neurons in one region of the brain with those in other regions. However, interneurons are generally considered to operate mainly within local brain areas. The interaction between interneurons allows the brain to perform complex functions such as learning and decision-making.
== Structure ==
In the human brain, approximately 20–30% of the neurons in the neocortex are interneurons, and the remaining majority of neurons are pyramidal. Investigations into the molecular diversity of neurons is impeded by the inability to isolate cell populations born at different times for gene expression analysis. An effective means of identifying coetaneous interneurons is neuronal birthdating. This can be achieved using nucleoside analogs such as EdU.
In 2008, a nomenclature for the features of GABAergic cortical interneurons was proposed, called Petilla terminology.
=== Spinal cord ===
Ia inhibitory interneuron: Found in lamina VII. Responsible for inhibiting antagonist motor neuron. 1a spindle afferents activate 1a inhibitory neuron.
Ib inhibitory interneuron: Found in lamina V, VI, VII. Afferent or Golgi tendon organ activates it.
=== Cortex ===
Parvalbumin-expressing interneurons
CCK-expressing interneurons
VIP-expressing interneurons
SOM-expressing interneurons
=== Cerebellum ===
Molecular layer (basket cells, stellate cells)
Golgi cells
Granule cells
Lugaro cells
Unipolar brush cells
=== Striatum ===
Parvalbumin-expressing interneurons
Cholinergic interneurons
Tyrosine hydroxylase-expressing interneurons
Calretinin-expressing interneurons
Nitric oxide synthase-expressing interneurons
== Function ==
Interneurons in the CNS are primarily inhibitory, and use the neurotransmitter GABA or glycine. However, excitatory interneurons using glutamate in the CNS also exist, as do interneurons releasing neuromodulators like acetylcholine.
In addition to these general functions, interneurons in the insect CNS play a number of specific roles in different parts of the nervous system, and also are either excitatory or inhibitory. For example, in the olfactory system, interneurons are responsible for integrating information from odorant receptors and sending signals to the mushroom bodies, which are involved in learning and memory. In the visual system, interneurons are responsible for processing motion information and sending signals to the optic lobes, which are involved in visual navigation.
Interneurons are also important for coordinating complex behaviors, such as flight and locomotion. For example, interneurons in the thoracic ganglia are responsible for coordinating the activity of the leg muscles during walking and flying.
Interneurons' main function is to provide a neural circuit, conducting flow of signals or information between sensory neurons and motor neurons.
== References == | Wikipedia/Interneuron |
A motor neuron (or motoneuron), also known as efferent neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly control effector organs, mainly muscles and glands. There are two types of motor neuron – upper motor neurons and lower motor neurons. Axons from upper motor neurons synapse onto interneurons in the spinal cord and occasionally directly onto lower motor neurons. The axons from the lower motor neurons are efferent nerve fibers that carry signals from the spinal cord to the effectors. Types of lower motor neurons are alpha motor neurons, beta motor neurons, and gamma motor neurons.
A single motor neuron may innervate many muscle fibres and a muscle fibre can undergo many action potentials in the time taken for a single muscle twitch. Innervation takes place at a neuromuscular junction and twitches can become superimposed as a result of summation or a tetanic contraction. Individual twitches can become indistinguishable, and tension rises smoothly eventually reaching a plateau.
Although the word "motor neuron" suggests that there is a single kind of neuron that controls movement, this is not the case. Indeed, upper and lower motor neurons—which differ greatly in their origins, synapse locations, routes, neurotransmitters, and lesion characteristics—are included in the same classification as "motor neurons." Essentially, motor neurons, also known as motoneurons, are made up of a variety of intricate, finely tuned circuits found throughout the body that innervate effector muscles and glands to enable both voluntary and involuntary motions. Two motor neurons come together to form a two-neuron circuit. While lower motor neurons start in the spinal cord and go to innervate muscles and glands all throughout the body, upper motor neurons originate in the cerebral cortex and travel to the brain stem or spinal cord. It is essential to comprehend the distinctions between upper and lower motor neurons as well as the routes they follow in order to effectively detect these neuronal injuries and localise the lesions.
== Development ==
Motor neurons begin to develop early in embryonic development, and motor function continues to develop well into childhood. In the neural tube cells are specified to either the rostral-caudal axis or ventral-dorsal axis. The axons of motor neurons begin to appear in the fourth week of development from the ventral region of the ventral-dorsal axis (the basal plate). This homeodomain is known as the motor neural progenitor domain (pMN). Transcription factors here include Pax6, OLIG2, Nkx-6.1, and Nkx-6.2, which are regulated by sonic hedgehog (Shh). The OLIG2 gene being the most important due to its role in promoting Ngn2 expression, a gene that causes cell cycle exiting as well as promoting further transcription factors associated with motor neuron development.
Further specification of motor neurons occurs when retinoic acid, fibroblast growth factor, Wnts, and TGFb, are integrated into the various Hox transcription factors. There are 13 Hox transcription factors and along with the signals, determine whether a motor neuron will be more rostral or caudal in character. In the spinal column, Hox 4-11 sort motor neurons to one of the five motor columns.
== Anatomy and physiology ==
=== Upper motor neurons ===
Upper motor neurons originate in the motor cortex located in the precentral gyrus. The cells that make up the primary motor cortex are Betz cells, which are giant pyramidal cells. The axons of these cells descend from the cortex to form the corticospinal tract. Corticomotorneurons project from the primary cortex directly onto motor neurons in the ventral horn of the spinal cord. Their axons synapse on the spinal motor neurons of multiple muscles as well as on spinal interneurons. They are unique to primates and it has been suggested that their function is the adaptive control of the hands including the relatively independent control of individual fingers. Corticomotorneurons have so far only been found in the primary motor cortex and not in secondary motor areas.
=== Nerve tracts ===
Nerve tracts are bundles of axons as white matter, that carry action potentials to their effectors. In the spinal cord these descending tracts carry impulses from different regions. These tracts also serve as the place of origin for lower motor neurons. There are seven major descending motor tracts to be found in the spinal cord:
Lateral corticospinal tract
Rubrospinal tract
Lateral reticulospinal tract
Vestibulospinal tract
Medial reticulospinal tract
Tectospinal tract
Anterior corticospinal tract
=== Lower motor neurons ===
Lower motor neurons are those that originate in the spinal cord and directly or indirectly innervate effector targets. The target of these neurons varies, but in the somatic nervous system the target will be some sort of muscle fiber. There are three primary categories of lower motor neurons, which can be further divided in sub-categories.
According to their targets, motor neurons are classified into three broad categories:
Somatic motor neurons
Special visceral motor neurons
General visceral motor neurons
==== Somatic motor neurons ====
Somatic motor neurons originate in the central nervous system, project their axons to skeletal muscles (such as the muscles of the limbs, abdominal, and intercostal muscles), which are involved in locomotion. The three types of these neurons are the alpha efferent neurons, beta efferent neurons, and gamma efferent neurons. They are called efferent to indicate the flow of information from the central nervous system (CNS) to the periphery.
Alpha motor neurons innervate extrafusal muscle fibers, which are the main force-generating component of a muscle. Their cell bodies are in the ventral horn of the spinal cord and they are sometimes called ventral horn cells. A single motor neuron may synapse with 150 muscle fibers on average. The motor neuron and all of the muscle fibers to which it connects is a motor unit. Motor units are split up into 3 categories:
Slow (S) motor units stimulate small muscle fibers, which contract very slowly and provide small amounts of energy but are very resistant to fatigue, so they are used to sustain muscular contraction, such as keeping the body upright. They gain their energy via oxidative means and hence require oxygen. They are also called red fibers.
Fast fatiguing (FF) motor units stimulate larger muscle groups, which apply large amounts of force but fatigue very quickly. They are used for tasks that require large brief bursts of energy, such as jumping or running. They gain their energy via glycolytic means and hence do not require oxygen. They are called white fibers.
Fast fatigue-resistant motor units stimulate moderate-sized muscles groups that do not react as fast as the FF motor units, but can be sustained much longer (as implied by the name) and provide more force than S motor units. These use both oxidative and glycolytic means to gain energy.
In addition to voluntary skeletal muscle contraction, alpha motor neurons also contribute to muscle tone, the continuous force generated by noncontracting muscle to oppose stretching. When a muscle is stretched, sensory neurons within the muscle spindle detect the degree of stretch and send a signal to the CNS. The CNS activates alpha motor neurons in the spinal cord, which cause extrafusal muscle fibers to contract and thereby resist further stretching. This process is also called the stretch reflex.
Beta motor neurons innervate intrafusal muscle fibers of muscle spindles, with collaterals to extrafusal fibres. There are two types of beta motor neurons: Slow Contracting- These innervate extrafusal fibers. Fast Contracting- These innervate intrafusal fibers.
Gamma motor neurons innervate intrafusal muscle fibers found within the muscle spindle. They regulate the sensitivity of the spindle to muscle stretching. With activation of gamma neurons, intrafusal muscle fibers contract so that only a small stretch is required to activate spindle sensory neurons and the stretch reflex. There are two types of gamma motor neurons: Dynamic- These focus on Bag1 fibers and enhance dynamic sensitivity. Static- These focus on Bag2 fibers and enhance stretch sensitivity.
Regulatory factors of lower motor neurons
Size Principle – this relates to the soma of the motor neuron. This restricts larger neurons to receive a larger excitatory signal in order to stimulate the muscle fibers it innervates. By reducing unnecessary muscle fiber recruitment, the body is able to optimize energy consumption.
Persistent Inward Current (PIC) – recent animal study research has shown that constant flow of ions such as calcium and sodium through channels in the soma and dendrites influence the synaptic input. An alternate way to think of this is that the post-synaptic neuron is being primed before receiving an impulse.
After Hyper-polarization (AHP) – A trend has been identified that shows slow motor neurons to have more intense AHPs for a longer duration. One way to remember this is that slow muscle fibers can contract for longer, so it makes sense that their corresponding motor neurons fire at a slower rate.
==== Special visceral motor neurons ====
These are also known as branchial motor neurons, which are involved in facial expression, mastication, phonation, and swallowing. Associated cranial nerves are the oculomotor, abducens, trochlear, and hypoglossal nerves.
==== General visceral motor neurons ====
These motor neurons indirectly innervate cardiac muscle and smooth muscles of the viscera ( the muscles of the arteries): they synapse onto neurons located in ganglia of the autonomic nervous system (sympathetic and parasympathetic), located in the peripheral nervous system (PNS), which themselves directly innervate visceral muscles (and also some gland cells).
In consequence, the motor command of skeletal and branchial muscles is monosynaptic involving only one motor neuron, either somatic or branchial, which synapses onto the muscle. Comparatively, the command of visceral muscles is disynaptic involving two neurons: the general visceral motor neuron, located in the CNS, synapses onto a ganglionic neuron, located in the PNS, which synapses onto the muscle.
All vertebrate motor neurons are cholinergic, that is, they release the neurotransmitter acetylcholine. Parasympathetic ganglionic neurons are also cholinergic, whereas most sympathetic ganglionic neurons are noradrenergic, that is, they release the neurotransmitter noradrenaline. (see Table)
=== Neuromuscular junctions ===
A single motor neuron may innervate many muscle fibres and a muscle fibre can undergo many action potentials in the time taken for a single muscle twitch. As a result, if an action potential arrives before a twitch has completed, the twitches can superimpose on one another, either through summation or a tetanic contraction. In summation, the muscle is stimulated repetitively such that additional action potentials coming from the somatic nervous system arrive before the end of the twitch. The twitches thus superimpose on one another, leading to a force greater than that of a single twitch. A tetanic contraction is caused by constant, very high frequency stimulation - the action potentials come at such a rapid rate that individual twitches are indistinguishable, and tension rises smoothly eventually reaching a plateau.
The interface between a motor neuron and muscle fiber is a specialized synapse called the neuromuscular junction. Upon adequate stimulation, the motor neuron releases a flood of acetylcholine (Ach) neurotransmitters from synaptic vesicles bound to the plasma membrane of the axon terminals. The acetylcholine molecules bind to postsynaptic receptors found within the motor end plate. Once two acetylcholine receptors have been bound, an ion channel is opened and sodium ions are allowed to flow into the cell. The influx of sodium into the cell causes depolarization and triggers a muscle action potential. T tubules of the sarcolemma are then stimulated to elicit calcium ion release from the sarcoplasmic reticulum. It is this chemical release that causes the target muscle fiber to contract.
In invertebrates, depending on the neurotransmitter released and the type of receptor it binds, the response in the muscle fiber could be either excitatory or inhibitory. For vertebrates, however, the response of a muscle fiber to a neurotransmitter can only be excitatory, in other words, contractile. Muscle relaxation and inhibition of muscle contraction in vertebrates is obtained only by inhibition of the motor neuron itself. This is how muscle relaxants work by acting on the motor neurons that innervate muscles (by decreasing their electrophysiological activity) or on cholinergic neuromuscular junctions, rather than on the muscles themselves.
=== Synaptic input to motor neurons ===
Motor neurons receive synaptic input from premotor neurons. Premotor neurons can be 1) spinal interneurons that have cell bodies in the spinal cord, 2) sensory neurons that convey information from the periphery and synapse directly onto motoneurons, 3) descending neurons that convey information from the brain and brainstem. The synapses can be excitatory, inhibitory, electrical, or neuromodulatory. For any given motor neuron, determining the relative contribution of different input sources is difficult, but advances in connectomics have made it possible for fruit fly motor neurons. In the fly, motor neurons controlling the legs and wings are found in the ventral nerve cord, homologous to the spinal cord. Fly motor neurons vary by over 100X in the total number of input synapses. However, each motor neuron gets similar fractions of its synapses from each premotor source: ~70% from neurons within the VNC, ~10% from descending neurons, ~3% from sensory neurons, and ~6% from VNC neurons that also send a process up to the brain. The remaining 10% of synapses come from neuronal fragments that are unidentified by current image segmentation algorithms and require additional manual segmentation to measure.
== See also ==
Betz cell
Central chromatolysis
Motor dysfunction
Motor neuron disease
Nerve
Sensory nerve
Motor nerve
Afferent nerve fiber
Efferent nerve fiber
Sensory neuron
== References ==
== Sources ==
Sherwood, L. (2001). Human Physiology: From Cells to Systems (4th ed.). Pacific Grove, CA: Brooks-Cole. ISBN 0-534-37254-6.
Marieb, E. N.; Mallatt, J. (1997). Human Anatomy (2nd ed.). Menlo Park, CA: Benjamin/Cummings. ISBN 0-8053-4068-8. | Wikipedia/Motor_neurons |
A multipolar neuron is a type of neuron that possesses a single axon and many dendrites (and dendritic branches), allowing for the integration of a great deal of information from other neurons. These processes are projections from the neuron cell body. Multipolar neurons constitute the majority of neurons in the central nervous system. They include motor neurons, and also interneurons (relay neurons), which are most commonly found in the cortex of the brain and the spinal cord. Peripherally, multipolar neurons are found in autonomic ganglia.
== See also ==
Dogiel cells
Ganglion cell
Purkinje cell
Pyramidal cell
== Additional images ==
== References ==
== External links ==
Diagram
Diagram
Image | Wikipedia/Multipolar_neuron |
Dopaminergic cell groups, DA cell groups, or dopaminergic nuclei are collections of neurons in the central nervous system that synthesize the neurotransmitter dopamine. In the 1960s, dopaminergic neurons or dopamine neurons were first identified and named by Annica Dahlström and Kjell Fuxe, who used histochemical fluorescence. The subsequent discovery of genes encoding enzymes that synthesize dopamine, and transporters that incorporate dopamine into synaptic vesicles or reclaim it after synaptic release, enabled scientists to identify dopaminergic neurons by labeling gene or protein expression that is specific to these neurons.
In the mammalian brain, dopaminergic neurons form a semi-continuous population extending from the midbrain through the forebrain, with eleven named collections or clusters among them.
== Cell group A8 ==
Group A8 is a small group of dopaminergic cells in rodents and primates. It is located in the midbrain reticular formation dorsolateral to the substantia nigra at the level of the red nucleus and caudally. In the mouse it is identified with the retrorubral field as defined by classical stains.
== Cell group A9 ==
Group A9 is the most densely packed group of dopaminergic cells, and is located in the ventrolateral midbrain of rodents and primates. It is for the most part identical with the pars compacta of the substantia nigra as seen from the accumulation of neuromelanin pigment in the midbrain of healthy, adult humans.
== Cell group A10 ==
Group A10 is the largest group of dopaminergic cells in the ventral midbrain tegmentum of rodents and primates. The cells are located for the most part in the ventral tegmental area, the linear nucleus and, in primates, the part of central gray of the midbrain located between the left and right oculomotor nuclear complexes.
== Cell group A11 ==
Group A11 is a small group of dopaminergic cells located in the posterior periventricular nucleus and the intermediate periventricular nucleus of the hypothalamus in the macaque. In the rat, small numbers of cells assigned to this group are also found in the posterior nucleus of hypothalamus, the supramammillary area and the reuniens nucleus. Dopaminergic cells in A11 may be important in the modulation of auditory processing.
== Cell group A12 ==
Group A12 is a small group of cells in the arcuate nucleus of the hypothalamus in primates. In the rat a few cells belonging to this group are also seen in the anteroventral portion of the paraventricular nucleus of the hypothalamus.
== Cell group A13 ==
Group A13 is distributed in clusters that, in the primate, are ventral and medial to the mammillothalamic tract of the hypothalamus; a few extend into the reuniens nucleus of the thalamus. In the mouse, A13 is located ventral to the mammillothalamic tract of the thalamus in the zona incerta.
== Cell group A14 ==
Group A14 consists of a few cells observed in and near the preoptic periventricular nucleus of the primate. In the mouse, cells in the anterodorsal preoptic nucleus are assigned to this group.
== Cell group A15 ==
Group A15 exists in a few species, such as sheep, and immunoreactive for tyrosine hydroxylase, a precursor of dopamine, in many other species including rodents and primates. It is located in ventral and dorsal components within the preoptic periventricular nucleus and adjacent parts of the anterior hypothalamic region. It is continuous caudally with the dopaminergic group A14.
== Cell group A16 ==
Group A16 is located in the olfactory bulb of vertebrates, including rodents and primates.
== Cell group Aaq ==
Group Aaq is a sparse group of cells located in the rostral half of the central gray of the midbrain in primates. It is more prominent in the squirrel monkey (Saimiri) than the macaque.
== Telencephalic group ==
This group is a population of cells immunoreactive for dopamine and tyrosine hydroxylase that are broadly distributed in the rostral forebrain, including such structures as: substantia innominata, diagonal band, olfactory tubercle, prepyriform area, striatum (at levels rostral to the anterior commissure), claustrum, and deep cortical layers of all gyri of the frontal lobe rostral to the head of the caudate nucleus; the cells are also numerous in intervening white matter, including the external capsule, extreme capsule and frontal white matter. They are found in the rodent, the macaque and the human.
== See also ==
Dopaminergic pathways
History of catecholamine research
== Footnotes ==
== References ==
Dahlstrom A, Fuxe K (1964). "Evidence for the existence of monoamine-containing neurons in the central nervous system". Acta Physiologica Scandinavica. 62: 1–55. PMID 14229500.
Dubach MF (1994). "11:Telencephalic dopamine cells in monkeys, humans and rats". In Smeets WJ, Reiner A (eds.). Phylogeny and Development of Catecholamine Systems in the CNS of Vertebrates. Cambridge, England: University Press. ISBN 978-0-5214-4251-0. OCLC 29952121.
Felten DL, Sladek Jr JR (1983). "Monoamine distribution in primate brain V. Monoaminergic nuclei: anatomy, pathways and local organization". Brain Research Bulletin. 10 (2): 171–284. doi:10.1016/0361-9230(83)90045-x. PMID 6839182.
Fuxe K, Hoekfelt T, Ungerstedt U (1970). "Morphological and functional aspects of central monoamine neurons". International Review of Neurobiology. 13: 93–126. doi:10.1016/S0074-7742(08)60167-1.
Nevue AA, Felix II RA, Portfors CV (November 2016). "Dopaminergic projections of the subparafascicular thalamic nucleus to the auditory brainstem". Hearing Research. 341: 202–209. doi:10.1016/j.heares.2016.09.001. PMC 5111623. PMID 27620513.
Paxinos G, Franklin KB (2001). The Mouse Brain in Stereotaxic Coordinates (2nd ed.). San Diego: Academic Press. ISBN 978-0-1254-7636-2. OCLC 493265554.
Smeets WJ, Reiner A (1994). "20:Catecholamines in the CNS of vertebrates: current concepts of evolution and functional significance". In Smeets WJ, Reiner A (eds.). Phylogeny and Development of Catecholamine Systems in the CNS of Vertebrates. Cambridge, England: University Press. ISBN 978-0-5214-4251-0. OCLC 29952121.{{cite book}}: CS1 maint: ref duplicates default (link)
Tillet Y (1994). "9: Catecholaminergic neuronal systems in the diencephalon of mammals". In Smeets WJ, Reiner A (eds.). Phylogeny and Development of Catecholamine Systems in the CNS of Vertebrates. Cambridge, England: University Press. ISBN 978-0-5214-4251-0. OCLC 29952121. | Wikipedia/Dopaminergic_neurons |
For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequence or, in replicating cells, by preventing addition of methyl groups to DNA so that the replicated DNA will largely have cytosine in the DNA sequence (5mC will be diluted out).
Methylated cytosine is frequently present in the linear DNA sequence where a cytosine is followed by a guanine in a 5' → 3' direction (a CpG site). In mammals, DNA methyltransferases (which add methyl groups to DNA bases) exhibit a strong sequence preference for cytosines at CpG sites. There appear to be more than 20 million CpG dinucleotides in the human genome (see genomic distribution). In mammals, on average, 70% to 80% of CpG cytosines are methylated, though the level of methylation varies with different tissues. Methylated cytosines often occur in groups or CpG islands within the promoter regions of genes, where such methylation may reduce or silence gene expression (see gene expression). Methylated cytosines in the gene body, however, are positively correlated with expression.
Almost 100% DNA demethylation occurs by a combination of passive dilution and active enzymatic removal during the reprogramming that occurs in early embryogenesis and in gametogenesis. Another large demethylation, of about 3% of all genes, can occur by active demethylation in neurons during formation of a strong memory. After surgery, demethylations are found in peripheral blood mononuclear cells at sites annotated to immune system genes. Demethylations also occur during the formation of cancers. During global DNA hypomethylation of tumor genomes, there is a minor to moderate reduction of the number of methylated cytosines (5mC) amounting to a loss of about 5% to 20% on average of the 5mC bases.
== Embryonic development ==
=== Early embryonic development ===
The mouse sperm genome is 80–90% methylated at its CpG sites in DNA, amounting to about 20 million methylated sites. After fertilization, the paternal chromosome is almost completely demethylated in six hours by an active process, before DNA replication (blue line in Figure).
Demethylation of the maternal genome occurs by a different process. In the mature oocyte, about 40% of its CpG sites in DNA are methylated. While somatic cells of mammals have three main DNA methyltransferases (which add methyl groups to cytosines at CpG sites), DNMT1, DNMT3A, and DNMT3B, in the pre-implantation embryo up to the blastocyst stage (see Figure), the only methyltransferase present is an isoform of DNMT1 designated DNMT1o. DNMT1o has an alternative oocyte-specific promoter and first exon (exon 1o) located 5' of the somatic and spermatocyte promoters. As reviewed by Howell et al., DNMT1o is sequestered in the cytoplasm of mature oocytes and in 2-cell and 4-cell embryos, but at the 8-cell stage is only present in the nucleus. At the 16 cell stage (the morula) DNMT1o is again found only in the cytoplasm. It appears that demethylation of the maternal chromosomes largely takes place by blockage of the methylating enzyme DNMT1o from entering the nucleus except briefly at the 8 cell stage. The maternal-origin DNA thus undergoes passive demethylation by dilution of the methylated maternal DNA during replication (red line in Figure). The morula (at the 16 cell stage), has only a small amount of DNA methylation (black line in Figure).
DNMT3b begins to be expressed in the blastocyst. Methylation begins to increase at 3.5 days after fertilization in the blastocyst, and a large wave of methylation then occurs on days 4.5 to 5.5 in the epiblast, going from 12% to 62% methylation, and reaching maximum level after implantation in the uterus. By day seven after fertilization, the newly formed primordial germ cells (PGC) in the implanted embryo segregate from the remaining somatic cells. At this point the PGCs have about the same level of methylation as the somatic cells.
=== Gametogenesis ===
The newly formed primordial germ cells (PGC) in the implanted embryo devolve from the somatic cells. At this point the PGCs have high levels of methylation. These cells migrate from the epiblast toward the gonadal ridge. As reviewed by Messerschmidt et al., the majority of PGCs are arrested in the G2 phase of the cell cycle, while they migrate toward the hindgut during embryo days 7.5 to 8.5. Then demethylation of the PGCs takes place in two waves. At day 9.5 the primordial germ cells begin to rapidly replicate going from about 200 PGCs at embryo day 9.5 to about 10,000 PGCs at day 12.5. During days 9.5 to 12.5 DNMT3a and DNMT3b are repressed and DNMT1 is present in the nucleus at a high level. But DNMT1 is unable to methylate cytosines during days 9.5 to 12.5 because the UHRF1 gene (also known as NP95) is repressed and UHRF1 is an essential protein needed to recruit DNMT1 to replication foci where maintenance DNA methylation takes place. This is a passive, dilution form of demethylation.
In addition, from embryo day 9.5 to 13.5 there is an active form of demethylation. As indicated below in "Molecular stages of active reprogramming," two enzymes are central to active demethylation. These are a ten-eleven translocation methylcytosine dioxygenase (TET) and thymine-DNA glycosylase (TDG). One particular TET enzyme, TET1, and TDG are present at high levels from embryo day 9.5 to 13.5, and are employed in active demethylation during gametogenesis. PGC genomes display the lowest levels of DNA methylation of any cells in the entire life cycle of the mouse at embryonic day 13.5.
== Learning and Memory ==
Learning and memory have levels of permanence, differing from other mental processes such as thought, language, and consciousness, which are temporary in nature. Learning and memory can be either accumulated slowly (multiplication tables) or rapidly (touching a hot stove), but once attained, can be recalled into conscious use for a long time. Rats subjected to one instance of contextual fear conditioning create an especially strong long-term memory. At 24 hours after training, 9.17% of the genes in the genomes of rat hippocampus neurons were found to be differentially methylated. This included more than 2,000 differentially methylated genes at 24 hours after training, with over 500 genes being demethylated. Similar results to that in the rat hippocampus were also obtained in mice with contextual fear conditioning.
The hippocampus region of the brain is where contextual fear memories are first stored (see figure of the brain, this section), but this storage is transient and does not remain in the hippocampus. In rats contextual fear conditioning is abolished when the hippocampus is subjected to hippocampectomy just one day after conditioning, but rats retain a considerable amount of contextual fear when hippocampectomy is delayed by four weeks. In mice, examined at 4 weeks after conditioning, the hippocampus methylations and demethylations were reversed (the hippocampus is needed to form memories but memories are not stored there) while substantial differential CpG methylation and demethylation occurred in cortical neurons during memory maintenance. There were 1,223 differentially methylated genes in the anterior cingulate cortex of mice four weeks after contextual fear conditioning. Thus, while there were many methylations in the hippocampus shortly after memory was formed, all these hippocampus methylations were demethylated as soon as four weeks later.
== Demethylation in Cancer ==
The human genome contains about 28 million CpG sites, and roughly 60% of the CpG sites are methylated at the 5 position of the cytosine. During formation of a cancer there is an average reduction of the number of methylated cytosines of about 5% to 20%, or about 840,00 to 3.4 million demethylations of CpG sites.
DNMT1 methylates CpGs on hemi-methylated DNA during DNA replication. Thus, when a DNA strand has a methylated CpG, and the newly replicated strand during semi-conservative replication lacks a methyl group on the complementary CpG, DNMT1 is normally recruited to the hemimethylated site and adds a methyl group to cytosine in the newly synthesized CpG. However, recruitment of DNMT1 to hemimethylated CpG sites during DNA replication depends on the UHRF1 protein. If UHRF1 does not bind to a hemimethylated CpG site, then DNMT1 is not recruited and cannot methylate the newly synthesized CpG site. The arginine methyltransferase PRMT6 regulates DNA methylation by methylating the arginine at position 2 of histone 3 (H3R2me2a). (See Protein methylation#Arginine.) In the presence of H3R2me2a UHRF1 can not bind to a hemimethylated CpG site, and then DNMT1 is not recruited to the site, and the site remains hemimethylated. Upon further rounds of replication the methylated CpG is passively diluted out. PRMT6 is frequently overexpressed in many types of cancer cells. The overexpression of PRMT6 may be a source of DNA demethylation in cancer.
== Molecular stages of active reprogramming ==
Three molecular stages are required for actively, enzymatically reprogramming the DNA methylome. Stage 1: Recruitment. The enzymes needed for reprogramming are recruited to genome sites that require demethylation or methylation. Stage 2: Implementation. The initial enzymatic reactions take place. In the case of methylation, this is a short step that results in the methylation of cytosine to 5-methylcytosine. Stage 3: Base excision DNA repair. The intermediate products of demethylation are catalysed by specific enzymes of the base excision DNA repair pathway that finally restore cystosine in the DNA sequence.
=== Stage 2 of active demethylation ===
Demethylation of 5-methylcytosine to generate 5-hydroxymethylcytosine (5hmC) very often initially involves oxidation of 5mC (see Figure in this section) by ten-eleven translocation methylcytosine dioxygenases (TET enzymes). The molecular steps of this initial demethylation are shown in detail in TET enzymes. In successive steps (see Figure) TET enzymes further hydroxylate 5hmC to generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Thymine-DNA glycosylase (TDG) recognizes the intermediate bases 5fC and 5caC and excises the glycosidic bond resulting in an apyrimidinic site (AP site). This is followed by base excision repair (stage 3). In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by APOBEC (AID/APOBEC) deaminases to form 5-hydroxymethyluracil (5hmU). Also, 5mC can be converted to thymine (Thy). 5hmU can be cleaved by TDG, MBD4, NEIL1 or SMUG1. AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield cytosine (Cyt). The TET family of dioxygenases are employed in the most frequent type of demethylation reactions.
==== TET family ====
TET dioxygenase isoforms include at least two isoforms of TET1, one of TET2 and three isoforms of TET3. The full-length canonical TET1 isoform appears virtually restricted to early embryos, embryonic stem cells and primordial germ cells (PGCs). The dominant TET1 isoform in most somatic tissues, at least in the mouse, arises from alternative promoter usage which gives rise to a short transcript and a truncated protein designated TET1s. The isoforms of TET3 are the full length form TET3FL, a short form splice variant TET3s, and a form that occurs in oocytes and neurons designated TET3o. TET3o is created by alternative promoter use and contains an additional first N-terminal exon coding for 11 amino acids. TET3o only occurs in oocytes and neurons and is not expressed in embryonic stem cells or in any other cell type or adult mouse tissue tested. Whereas TET1 expression can barely be detected in oocytes and zygotes, and TET2 is only moderately expressed, the TET3 variant TET3o shows extremely high levels of expression in oocytes and zygotes, but is nearly absent at the 2-cell stage. It is possible that TET3o, high in neurons, oocytes and zygotes at the one cell stage, is the major TET enzyme utilized when very large scale rapid demethylations occur in these cells.
=== Stage 1 of demethylation - recruitment of TET to DNA ===
The TET enzymes do not specifically bind to 5-methylcytosine except when recruited. Without recruitment or targeting, TET1 predominantly binds to high CG promoters and CpG islands (CGIs) genome-wide by its CXXC domain that can recognize un-methylated CGIs. TET2 does not have an affinity for 5-methylcytosine in DNA. The CXXC domain of the full-length TET3, which is the predominant form expressed in neurons, binds most strongly to CpGs where the C was converted to 5-carboxycytosine (5caC). However, it also binds to un-methylated CpGs.
For a TET enzyme to initiate demethylation it must first be recruited to a methylated CpG site in DNA. Two of the proteins shown to recruit a TET enzyme to a methylated cytosine in DNA are OGG1 (see figure Initiation of DNA demethylation at a CpG site) and EGR1.
==== OGG1 ====
Oxoguanine glycosylase (OGG1) catalyses the first step in base excision repair of the oxidatively damaged base 8-OHdG. OGG1 finds 8-OHdG by sliding along the linear DNA at 1,000 base pairs of DNA in 0.1 seconds. OGG1 very rapidly finds 8-OHdG. OGG1 proteins bind to oxidatively damaged DNA with a half maximum time of about 6 seconds. When OGG1 finds 8-OHdG it changes conformation and complexes with 8-OHdG in its binding pocket. OGG1 does not immediately act to remove the 8-OHdG. Half maximum removal of 8-OHdG takes about 30 minutes in HeLa cells in vitro, or about 11 minutes in the livers of irradiated mice. DNA oxidation by reactive oxygen species preferentially occurs at a guanine in a methylated CpG site, because of a lowered ionization potential of guanine bases adjacent to 5-methylcytosine. TET1 binds (is recruited to) the OGG1 bound to 8-OHdG (see figure). This likely allows TET1 to demethylate an adjacent methylated cytosine. When human mammary epithelial cells (MCF-10A) were treated with H2O2, 8-OHdG increased in DNA by 3.5-fold and this caused about 80% demethylation of the 5-methylcytosines in the MCF-10A genome.
==== EGR1 ====
The gene early growth response protein 1 (EGR1) is an immediate early gene (IEG). EGR1 can rapidly be induced by neuronal activity. The defining characteristic of IEGs is the rapid and transient up-regulation—within minutes—of their mRNA levels independent of protein synthesis. In adulthood, EGR1 is expressed widely throughout the brain, maintaining baseline expression levels in several key areas of the brain including the medial prefrontal cortex, striatum, hippocampus and amygdala. This expression is linked to control of cognition, emotional response, social behavior and sensitivity to reward. EGR1 binds to DNA at sites with the motifs 5′-GCGTGGGCG-3′ and 5'-GCGGGGGCGG-3′ and these motifs occur primarily in promoter regions of genes. The short isoform TET1s is expressed in the brain. EGR1 and TET1s form a complex mediated by the C-terminal regions of both proteins, independently of association with DNA. EGR1 recruits TET1s to genomic regions flanking EGR1 binding sites. In the presence of EGR1, TET1s is capable of locus-specific demethylation and activation of the expression of downstream genes regulated by EGR1.
== DNA demethylation intermediate 5hmC ==
As indicated in the Figure above, captioned "Demethylation of 5-methylcytosine," the first step in active demethylation is a TET oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). The demethylation process, in some tissues and at some genome locations, may stop at that point. As reviewed by Uribe-Lewis et al., in addition to being an intermediate in active DNA demethylation, 5hmC is often a stable DNA modification. Within the genome, 5hmC is located at transcriptionally active genes, regulatory elements and chromatin associated complexes. In particular, 5hmC is dynamically changed and positively correlated with active gene transcription during cell lineage specification, and high levels of 5hmC are found in embryonic stem cells and in the central nervous system. In humans, defective 5-hydroxymethylating activity is associated with a phenotype of lymphoproliferation, immunodeficiency and autoimmunity.
=== Stage 3 base excision repair ===
The third stage of DNA demethylation is removal of the intermediate products of demethylation generated by a TET enzyme by base excision repair. As indicated above in Stage 2, after 5mC is first oxidized by a TET to form 5hmC, further oxidation of 5hmC by TET yields 5fC and oxidation of 5fC by TET yields 5caC. Both 5fC and 5caC are recognized by a DNA glycosylase, TDG, a base excision repair enzyme, as an abnormal base. As shown in the Figure in this section, TDG removes the abnormal base (e.g. 5fC) while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. In this Figure, the 8-OHdG is left in the DNA, since it may have been present when OGG1 attracted TET1 to the CpG site with a methylated cytosine. After an AP site is formed, AP endonuclease creates a nick in the phosphodiester backbone of the AP site that was formed when the TDG DNA glycosylase removed the 5fC or 5caC. The human AP endonuclease incises DNA 5′ to the AP site by a hydrolytic mechanism, leaving a 3′-hydroxyl and a 5′-deoxyribose phosphate (5' dRP) residue. This is followed by either short patch or long patch repair. In short patch repair, 5′ dRP lyase trims the 5′ dRP end to form a phosphorylated 5′ end. This is followed by DNA polymerase β (pol β) adding a single cytosine to pair with the pre-existing guanine in the complementary strand and then DNA ligase to seal the cut strand. In long patch repair, DNA synthesis is thought to be mediated by polymerase δ and polymerase ε performing displacement synthesis to form a flap. Pol β can also perform long-patch displacement synthesis. Long-patch synthesis typically inserts 2–10 new nucleotides. Then flap endonuclease removes the flap, and this is followed by DNA ligase to seal the strand. At this point there has been a complete replacement of the 5-methylcytosine by cytosine (demethylation) in the DNA sequence.
== Demethylation after exercise ==
Physical exercise has well established beneficial effects on learning and memory (see Neurobiological effects of physical exercise). BDNF is a particularly important regulator of learning and memory. As reviewed by Fernandes et al., in rats, exercise enhances the hippocampus expression of the gene Bdnf, which has an essential role in memory formation. Enhanced expression of Bdnf occurs through demethylation of its CpG island promoter at exon IV and this demethylation depends on steps illustrated in the two figures.
== Demethylation after exposure to traffic related air pollution ==
In a panel of healthy adults, negative associations were found between total DNA methylation and exposure to traffic related air pollution. DNA methylation levels were associated both with recent and chronic exposure to Black Carbon as well as benzene.
== Peripheral sensory neuron regeneration ==
After injury, neurons in the adult peripheral nervous system can switch from a dormant state with little axonal growth to robust axon regeneration. DNA demethylation in mature mammalian neurons removes barriers to axonal regeneration. This demethylation, in regenerating mouse peripheral neurons, depends upon TET3 to generate 5-hydroxymethylcytosine (5hmC) in DNA. 5hmC was altered in a large set of regeneration-associated genes (RAGs), including well-known RAGs such as Atf3, Bdnf, and Smad1, that regulate the axon growth potential of neurons.
== See also ==
DNA methylation
DNA demethylation
== References == | Wikipedia/DNA_demethylation |
Rosehip neurons are inhibitory GABAergic neurons present in the first layer (the molecular layer) of the human cerebral cortex. They make up about 10-15% of all inhibitory neurons in Layer 1. Neurons of this type (having "large ‘rosehip’-like axonal boutons and compact arborization") exist in humans, but have not been reported in rodents.
Rosehip neurons are named after the rose hip fruit due to the axon terminal's resemblance to their berries.
These rosehip cells show an immunohistochemical profile (GAD1+CCK+, CNR1–SST–CALB2–PVALB–) matching a single transcriptomically defined cell type whose specific molecular marker signature is not seen in mouse cortex. Rosehip cells in layer 1 make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons, and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.
== Discovery ==
An international group of scientists discovered Rosehip neurons and announced their discovery in August 2018. These authors contributed equally to this work: Eszter Boldog (University of Szeged, Szeged, Hungary), Trygve E. Bakken (Allen Institute for Brain Science, Seattle, WA, United States), and Rebecca D. Hodge (Allen Institute for Brain Science, Seattle, WA, United States). They identified this cell with the help of RNA sequencing.
== See also ==
Endorestiform nucleus, a nucleus discovered in 2018 which is uniquely present in human.
== References == | Wikipedia/Rosehip_neuron |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.