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A | Welcome to the Huberman Lab podcast, where we discuss science and science based tools for everyday life. |
B | I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today I have the pleasure of introducing the first guest of the Huberman Lab podcast. My guest is Doctor Carl Deisseroth. Doctor Karl Deisseroth is a medical doctor. He's a psychiatrist and a research scientist. |
A | At Stanford School of Medicine. |
B | In his clinical practice, he sees patients dealing with a range of nervous system disorders, including obsessive compulsive disorder, autism, attention deficit disorders, schizophrenia, mania, anxiety disorders, and eating disorders. His laboratory develops and explores tools with which to understand how the nervous sy... |
A | Brain works more generally. |
B | We also discuss issues of consciousness, and we even delve into how somebody like Carl, who's managing a full time clinical practice and a 40 plus person laboratory and a family of five children and is happily married, how he organizes his internal landscape his own thinking in order to manage that immense workload and... |
A | And his pursuits in science. |
B | I found this to be an incredible conversation. I learned so much. I also learned through the course of reading Carl's book projections that not only is he an accomplished psychiatrist and obviously an accomplished research scientist and a family man, but he's also a phenomenal writer. Projections is absolutely, masterf... |
A | Biological system relevant to health throughout your brain and body. |
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A | They're all delicious. |
B | So again, if you want to try elemnt, you can go to elementlmnt.com Huberman Today's episode is also brought to us by waking up. Waking up is a meditation app that includes hundreds of meditation programs, mindfulness trainings, yoga Nidra sessions, and NSDR non sleep deep rest protocols. I started using the Waking up a... |
A | App turned out to be the waking. |
B | Up app, which could teach you meditations of different durations, and that had a lot of different types of meditations to place the brain and body into different states and that he liked it very much. So I gave the waking up app a try, and I too found it to be extremely useful because sometimes I only have a few minute... |
A | And now my conversation with doctor Carla Diceroth. Well, thanks for being here. |
C | Thanks for having me. |
A | It's been a long time coming for me, because you may not know this, but one of the reasons I started this podcast was actually so I could have this conversation. It's but one. There are other reasons, but one of the goals is to be able to hold conversations with colleagues of mine that are doing incredible work in the ... |
C | Well, you know, I'm married to a neurologist and I am a psychiatrist, and we make fun of each other all the time. So this is a lot of neuroscientists and a lot of brain clinicians actually think these two should be the same field at some point in the future. They were in the past. They started together. Psychiatry, tho... |
A | So do you find that if a patient is very verbal or hyper verbal, that you have an easier time diagnosing them, as opposed to somebody who's more quiet and reserved, or I can imagine the opposite might be true as well. |
C | Well, because we only have words, you put your finger on a key point. If they don't speak that much, in principle, it's harder. The lack of speech can be a symptom. We can see that in depression. We can see that in the negative symptoms of schizophrenia. We can see that in autism. Sometimes by itself, that is a symptom... |
A | Do you find that there are patients that have, let's call them comorbidities or conditions where they would land in both psychiatry and neurology, meaning there's damage to a particular area of the brain, and therefore they're depressed. And how do you tease that out as a psychiatrist? |
C | Yeah, this happens all the time. Parkinson's disease is a great example. It can be debilitating in so many ways. People have trouble moving, they have trouble walking, trouble swallowing, and they can have truly severe depression. And this is, you might say, oh, well, they've got a life threatening illness. But there a... |
A | Do you think we will ever have a blood test for depression or schizophrenia or autism? And would that be a good or a bad thing? |
C | I think ultimately there will be quantitative tests. Already, efforts are being made to look at certain rhythms in the brain. Using external eegs to look at brain waves effectively, look at the ratios of certain frequencies to other frequencies, and there's some progress being made on that front. It's not as good as it... |
A | I want to know, and I'm sure there are several, but what do you see as the biggest challenge facing psychiatry and the treatment of mental illness today? |
C | I think we have. We're making progress on what the biggest challenge is, which I think there's still such a strong stigma for psychiatric disease that patients often don't come to us, and they feel that they should be able to handle this on their own. And that can slow treatment. It can lead to worsening symptoms. We k... |
A | That raises a question related to something I heard you say many years ago at a lecture, which was that this was a scientific lecture, and you said, we don't know how other people feel. Most of the time, we don't even really know how we feel. Maybe you could elaborate on that a little bit of the dearth of ways that we ... |
C | This is really interesting. Here we have it. There's a tension between the words that we've built up in the clinic that mean something to the physicians. And then there's the colloquial use of words that may not be the same. And so that's the first level we have to sort out. When someone says, you know, I'm. I'm depres... |
A | So in this area of trying to figure out what's going on under the hood through words. It sounds like certain words would relate to this idea of anticipation and hope. Is it fair to say that that somehow relates to the dopamine system in the sense that dopamine is involved in motivated behaviors? I mean, is that in. If ... |
C | Absolutely. |
A | And there are now ways to measure the accuracy of those statements. Like, for instance, if I gave you permission, you could know if I slept last night or whether or not I was just saying I had a poor night's sleep. |
C | Yes, that's right. |
A | So in moving forward through 2021 and into the next ten and 100 years of psychiatry, do you think that the body reporting some of the actions of a human are going to become useful and mesh with the words in a way that's going to make your job easier? |
C | I do think that's true. And these, the two things you've mentioned, eating and sleeping, those are additional criteria that we use to diagnose depression. These are the vegetative signs, we call them of depression, poor sleep and poor eating. And if you have a baseline for somebody, that's the real challenge, though. W... |
A | Of measuring one's own behavior. You know, I I've heard of work that's going on. Sam golden up at the University of Washington, who works on aggression in animal models, was telling me that there's some efforts that he's making, and perhaps you're involved in this work as well. I don't know of devices that would allow ... |
C | Yeah, that I do like. Because that gives the patient the agency to detect what's going on. Even separate from modern technology. This has been part of the art of psychiatry, is to help patients realize that sometimes other people observing them can give them the earliest warning signs of depression. We see this very of... |
A | So this is like 02:00 a.m. 03:00. |
C | A.M. it could start. Yeah, it could start at 05:00 a.m. |
A | Could go to four and unable to fall back asleep. |
C | Unable to fall back asleep. Exactly. So that's. And that they may not know what to do with that. It could just be, from their perspective, it's just something that's happening. But if you put enough of that information together, that that could be a useful warning sign for the patient, and it could help them seek treat... |
A | Interesting. So in this framework of needing words to self report or machines to detect how we feel or maybe inform a psychiatrist how a patient feels, I want to touch on some of the technologies that you've been involved in building but as a way to march into that, are there any very good treatments for psychiatric di... |
C | Yes. Yeah, we are fortunate. And this coming back to my, you know, the joking between my wife and myself in terms of neurology and psychiatry, we actually, in psychiatry, despite the depths of the mystery we struggle with, many of our treatments are actually, we may be doing better than some other specialties in terms ... |
A | How long does something like that take. |
C | On average, for a motivated, insightful patient? You can have a very cookbooky series of sessions, six to twelve sessions, or even less for someone who's very ingest, insightful and motivated, and it can have a very powerful effect that quickly. And that's just with words. There are many psychiatric medications that ar... |
A | These, we should clarify positive symptoms. You mean not positive in the qualitative sense, you mean positive meaning that the appearance of something abnormal. |
C | Exactly, yeah. And thank you for that clarification. When we say positive symptoms, we do mean the addition of something that wasn't there before, like a hallucination or a paranoia. And that stands in contrast to the negative symptoms where something is taken away. And these are patients who are withdrawn. They have w... |
A | So what are the pieces that are going to be required to cure autism, cure Parkinson's, cure schizophrenia? I would imagine there are several elements and bins here. Understanding the natural biology, understanding what the activity patterns are, how to modify those. Maybe you could just tell us what you think. What is ... |
C | I think the first thing we need is understanding. We need. Almost every psychiatric treatment has been serendipitously identified. Just noting by chance that something that was done for some person also had. |
A | A side effect, like lithium or something. |
C | Like lithium is a good example. |
A | Is it true that it was the urine of guinea pigs given lithium that was given to manic patients that made them not manic? Is that true? |
C | I don't have firsthand knowledge of that, but I would defer that. But it's true for essentially every treatment. The antidepressants originally arose as anti tuberculosis drugs, for example. |
A | I did not know that. |
C | This is a classic example for. And this is across all of psychiatry, and of course, there's the seizures as well. That was noticed, that patients who had epilepsy or had a seizure and also had depression, that they became much, at least for a while, they were improved after the seizure. |
A | That's amazing. I don't want to take you off course of the question, answering the question I asked, but I've heard before that if autistic children get a fever, that their symptoms improve. Is that true? |
C | I've done a fair bit of work with autism in my clinical practice. I work with adult autism, and I have heard statements like that and descriptions like that from patients and their families. That is very hard to study quantitatively because often with the children, you have this. Not as quantitative as you'd like, coll... |
A | So that seems like the first to me, the first bin of this, what I call the bento box, for lack of a better analogy, that we need to know the circuits, we need to know the cells in the various brain regions and portions of the body and how they connect to one another and what the patterns of activity are under a normal,... |
C | Well, this is, a, first of all, I give nature the credit for creating channelrhodopsins. These are beautiful little proteins that are made by algae, single celled green algae. And it's a great story in basic science that our understanding of animal behavior, sensation, cognition and action in our brains, all the way ba... |
A | And I must say, it was quite an honor and a privilege to watch optogenetics move from idea to discovery to the laboratory. I think we were postdocs at the same time, which is living proof that people move at different rates. That's a joke at my expense, by the way. We end up in the same spot, more or less physically, i... |
C | Yeah. So this is, you know, this whole thing, you know, it's been about now going on 17 years, that we've been putting channelrhodopsins into neurons. It started just like Andre from Ensign's work in a dish by 2000, that was in 2004. In 2007, we were putting these into behaving mice, and we were able to, with the switc... |
A | So basically, you're controlling the mouse's behavior? |
C | Yeah, exactly. In real time. So we could make a mouse that was just sitting there doing nothing to then turn left very consistently, in fact, go around in a circle, and as soon as we turn off the light, it would stop. That was an eye opening moment. It took, really, a few years to make optogenetics work. There was a lo... |
A | An amazing paper and discovery. I realize it was one patient, but it's such an important milestone. |
C | Well, as you say, it's a very important milestone, and the history of that is very deep. Almost ten years earlier, Botan Raska and I had published a paper in Science in human retina, but explanted, taken from cadavers, from someone who had died, the living retina taken out opsins, put into this retinal tissue and showi... |
A | You and I know Botan well, and you and Botan share this incredible big vision that I think only a clinician can really understand, being in close contact with and the suffering of patients as a ultimate motivator of developing technologies. Which makes me have to ask, did you decide to become a scientist to find cures ... |
C | No, I didn't. It's a really important question to actually look back and see the steps that brought you to a particular place. And that was not what brought me initially to science. And it's okay to, I think, to embrace the twists and turns that life brings to you. But I was always interested in the brain. And so that ... |
A | Front of him, even though their vision was perfectly fine. |
C | Even though their vision was perfectly fine. Exactly. And so I was, and I loved the operating room. I loved the rhythm of suturing and the precision of it. And I loved being able to help patients immediately. But then a required rotation was in psychiatry, which I was not looking forward to at all. And that completely ... |
A | It all started with poetry, and it started with poetry out of respect for poetry. Are there any favorites that you spend time with on a regular basis? |
C | I mean, the ones who got me down this path early on. I remember in childhood, in high school, Borges had an immense influence on me. I studied Spanish all the way through and reading his work. He was a great writer. He wrote both in English and in Spanish, and being able to appreciate his poetry, both in English and in... |
A | You're bilingual. |
C | I wouldn't say now. I became. At one point, I was effectively fluent in Spanish, and I'm pretty good with medical Spanish still, because we use Spanish all the time in the clinic here. I wouldn't claim full fluency, but it's something I definitely use all the time that's been very helpful in the clinic. |
A | Borges is wonderful. As the son of an argentine, I grew up hearing about it, and I learned that Borges favorite city was Geneva. So I spent time in Geneva only for that reason. It also turns out to be an interesting city. So you developed methods to control neurons with these algae proteins using light. In 2015, there ... |
C | Yeah. So starting with the body is a good example because it, it highlights the opportunity and how far we have to go. So let's take this example of vagus nerve stimulation. So the vagus nerve, it's the 10th cranial nerve. It comes from the brain. It goes down, it innervates the heart, innervates the gut. And by innerv... |
A | And why the vagus? I mean, it's there, but, and it's accessible. |
C | That's the reason? |
B | That's the reason? |
C | That's the reason, yes. |
B | Really? |
C | Yeah. |
A | You're not kidding? |
C | I'm not kidding. |
A | So stimulating the vegas to treat depression simply because it's accessible, it started as. |
C | Actually as an epilepsy treatment. And it can help with epilepsy, but. |
A | Yes, you gotta love medicine. As a scientist, I got, this is where I get to chuckle and just say, I'm in the field of medicine from that perspective, from the perspective of a scientist and outsider, the field of medicine as a field that goes in and tickles pathways because they're there. I don't know what to say. It's... |
C | Yeah, I mean, there are stories people tell. So the vagus nerve lands on a particular spot on the brain called the solitary tract nucleus, which is just one synapse away from the serotonin and the dopamine and the norepinephrine. |
A | So there's a link to chemical systems in the brain that make it a rational choice? |
C | Yes. It's not irrational, but I can tell you that even if that were not true, the same thing would have been tried. You guys would have done it anyway because it's successful. I see. Okay. And. And. But. And why? Well, it's. It's not to, again, not to disparage what. What's been happening in this branch of medicine. Th... |
A | How do you think it's working? When it does work? Is it triggering the activation of neurons that release more serotonin or dopamine? |
C | It could be, but I would say we don't have evidence for that. And so I just don't know. But what is clear is that it's dose limited in how high and strongly we can stimulate. And why? It's because it's an electrode and it's stimulating everything nearby. And when you turn on the vagus nerve stimulator, the patient's vo... |
A | We want to fix this key on the piano. And then I see two other steps that are required. One is to get the channel opsin gene into the cell. In the case of botan, Roscoe and colleagues rescuing vision in this patient, they did that by an injection of a virus that doesn't damage the neurons. The virus itself is fairly in... |
C | Yeah. So we had to solve exactly these questions. You're saying, how do you get the light in? How do you get the gene in in a potent and robust and safe way. And that's now solved, and that's not a challenge. So there are very safe, well tolerated gene delivery mechanisms that are called adeno associated viruses, aavsi... |
A | Would that be an outpatient procedure? |
C | Yeah. |
A | So you come in in the morning, get your injection, maybe walk out a few hours later? |
C | Yeah, that's right. And so that's the gene, then the light delivery. This is also something that we've worked out. We've worked on making very, very light sensitive opsins. One challenge, and Botan would be the first to state this. In fact, in solving this problem for the patient, he had to build goggles that created m... |
A | And it has to be the right wavelength. |
C | Has to be the right. |
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