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Speaker A: Welcome to the Huberman Lab podcast, where we discuss science and science based tools for everyday life. 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 Doctor Robert Sapolsky. Doctor Sapolsky is a professor ... |
Speaker B: Glad to be here. |
Speaker A: There's an enormous range of topics that we could drill into, but just to start off, I want to return to a topic that is near and dear to your heart, which is stress. And one of the questions that I get most commonly is, what is the difference between short and long term stress. In terms of their benefits an... |
Speaker B: Well, basically, sort of two graphs that one would draw. The first one is just all sorts of beneficial effects of stress short term. And then once we get into chronicity, it's just downhill from there. Short term because it saves you from the predator, short term because you're giving a presentation and you ... |
Speaker A: Us aim for in terms of the benefits of stress in the short term. One thing that's really striking to me is how physiologically the stress response looks so much like the excitement response to a positive event. And we can speculate that the fundamental difference between short term stress and short term exci... |
Speaker B: On a really mechanical level, if you're in a circumstance that is requiring that your heart races and youre. You're breathing as fast and you're using your muscles and some such thing, you're going to be having roughly the same brain activation profile, whether this is for something wonderful or something te... |
Speaker A: Let's use the amygdala as a transition point to another topic that you've spent many years working on and thinking about, which is testosterone and other sex steroid hormones. I heard you say once before that among all the brain areas that bind testosterone, where testosterone can park and create effects, th... |
Speaker B: The brain and pertinent to the transition from whether this is a stressor that's evoking fear or evoking aggression in terms of that continuum? Also, because the amygdala is in the center of all four points on those axes, basically, almost everybody out there has a completely wrong idea as to what testostero... |
Speaker A: Your social setting, in terms of status and the relationship between individuals, either non human primates or humans. Can we say that testosterone and levels of testosterone, or I should say, can we say that relative levels of testosterone between individuals is correlated to status within the hierarchy? |
Speaker B: Yes. But in a way that winds up being totally uninteresting. Like, you go back, I don't know, whatever number of decades, the endocrinology texts, and there were two totally reliable findings in there. Let's see. I have a dog in here. That's good. |
Speaker A: We like dogs. At the Huberman Lab podcast, he's jingling a bit. They are welcome. They are absolutely welcome. Yeah. |
Speaker B: And there'd be two truisms. Which is higher levels of testosterone predict higher levels of aggression in humans and other animals. Higher levels of testosterone predict higher levels of sexual activity. Whoa. Testosterone causing both. And the correlation is there. And when you look closely, we got cause an... |
Speaker A: Very interesting. I think that there are a lot of misconceptions about human biology, but testosterone seems to be one area where, at least from what I can find on the Internet, it's sort of at the peak of misunderstanding. Maybe we could just ask a few more questions about testosterone and sexual behavior, ... |
Speaker B: The opposite direction of the causality? |
Speaker A: Yeah, yeah, yeah. So if I were to increase somebody's testosterone by 30%, male or female, doesn't matter. Their sexual behavior may or may not. |
Speaker B: Change essentially zero effect at all. Your brain is not that sensitive to fluctuations in testosterone levels in terms of things like aggression, raising testosterone. Just a great footnote. If you have the right type of willing to die in the trenches devotion sort of thing, watching your favorite team play... |
Speaker A: Very interesting. Can we say that there's an exception in terms of the early organizing effects of hormones. Like, for instance, if a developing animal is deprived of testosterone or estrogen or aromatized testosterone into estrogen. There's a whole story there. As you know, then I could imagine that the cir... |
Speaker B: Yeah, exactly. And a great way of seeing that is this totally nutty biological factoid, which is the second to fourth digit ratio in hands. Oh, yeah, totally obscure thing. The ratio of one to the other in some way reflects levels of testosterone androgen exposure during fetal life. And I can't remember whic... |
Speaker A: Yeah, I have a confession, which is that I was a master's student at Berkeley, and Mark Breed loves arena. So I'm an author on that paper, although I'm deep within the author line, and you got the description of it exactly right, that it's the d two. The index finger to the ring finger ratio is more similar ... |
Speaker B: Type of post parturition period after birth. Aggression is all about estrogen, progesterone, those sorts of things. Female aggression the rest of the time has testosterone as a major player at a much lower level. On the average. On the average, one always has to say, but it's basically the same punchlines in... |
Speaker A: So, in line with that, how should we conceptualize testosterone? I realize there isn't a single sentence that can capture a hormone and all its effects, because hormones have so many different slow and fast effects on the brain, on other glands, on their own, on the very glands that produce them. As I've hea... |
Speaker B: Yeah, maybe. Three separate answers to that. The first one is, I think it's a fair summary to think that when it comes to motivated, strong behaviors, what testosterone does is make you more of whatever you already are in that domain, sexual arousal, libido aggressiveness, spontaneous aggression, reactive ag... |
Speaker A: Super interesting. I always think about testosterone and dopamine being close cousins in the brain, not just because of their relationship through the pituitary and hypothalamus. That, of course, but also because of dopamine's salient role in creating this bias towards exteroception. When somebody takes a dr... |
Speaker B: Well, I think it's got lots to do with sort of this massive revisionism about dopamine. Everyone since the pharaohs got brought up being taught that dopamine is about pleasure and reward. Turns out it isn't. It's about anticipation of reward, and it's about generating the motivation, the goal directed behavi... |
Speaker A: Yeah. Such beautiful biology there. And I love the way you encapsulate their relationship. I want to ask about estrogen. We don't hear about estrogen as often. And it's always interesting to me now, doing some public facing education, that testosterone is this very controversial molecule. Just to say it is a... |
Speaker B: No. And it's, once again, very context dependent. And if estrogen, after giving birth, is playing a central role and you wanting to shred the face of somebody getting too close to your kittens kind of thing, we know it's not just warm, fuzzy, empathic kind of stuff. Estrogen, in lots of ways, could be summar... |
Speaker A: Wow, that's fascinating. And I never thought that these steroid hormone receptors could, by not binding estrogen, being devoid of estrogen binding, I should say, could then set off opposite biochemical cascades. Fascinating. I guess it raises the question about testosterone replacement, too, whether or not p... |
Speaker B: Two additional miseries, complications so, okay, you're trying to understand. You look at women with a history, with or without postmenopausal estrogen replacement, where it's done right, and you're seeing 20 years later estrogen is a predictor of a decreased risk of Alzheimer's. Then you got to start trying... |
Speaker A: Yeah, I don't know what to make of the literature on dropping rates of testosterone and endocrine disruptors. I was at Berkeley when Tyrone Hayes published his data on these frogs that were drinking water from various locations throughout the United States, not just in California, and seeing very severe endo... |
Speaker B: No, the phenomenon does appear to be quite real. Cross sectional studies, human populations, or I still don't understand why this was one of the first things that Hayes spotted decreasing testicle size and crocodile, go figure. Why that was one of the first contributions to this. And I think the phenomenon i... |
Speaker A: Yeah, it's an area that I know there's a lot of interest in. And you've got groups of people who won't touch a receipt at a store because of the bpas that are on the inks of the. And then you've got people who don't care about those things. It is a fascinating area, and I hope that more biology will be done ... |
Speaker B: And what you see is, rat number one gets all the benefits of exercise. Rat number two gets all the downsides of severe stress with the same exact muscle expenditure and movements going on. Perfectly yoked. Great example that. It's the interpretation in your head, and I haven't kept up with that literature, b... |
Speaker A: Interesting. These days there's a lot of interest in using physical practices to mitigate stress, you know, trying to get out of the ruminating and to some extent take control of neural circuits in the brain by using exercise and using breathing and hypnosis. And of course, hypnosis has a mental component as... |
Speaker B: That makes some sense physiologically preconditioning for when the real stressors come in terms of what you bring up. Oh, transcendental meditation, mindfulness exercise, prayer, sort of reflecting on gratitude, all that sort of thing. Collectively, they work on the average, they work in terms of they can lo... |
Speaker A: Yeah. Amen. I think one of the core goals of my lab and David Spiegel's lab, and I know you've worked with David and published papers with David as well, is to really try and find out what are the various entry points to this thing that we call the autonomic nervous system and the stress system and these sys... |
Speaker B: Benign for those people who were stuck around you. |
Speaker A: Right, right. Absolutely. And that brings me to this question of I find it amazing that how we perceive an event and whether or not we chose to be in that event or not, can have such incredibly different effects on circuitry of the brain and circuitry of the body and biology of cells. And in some ways, it bo... |
Speaker B: Well, all you need to do is, like tonight, before you're going to sleep and you're lying in bed and you're nice and drowsy, and your heart's beating nice and slow, you start thinking about the fact that that heart isn't going to beat forever. And imagine your toes getting cold afterward, and imagine the flow... |
Speaker A: Yeah. The prefrontal cortex, this thinking machinery that we all harbor, it's such a double edged sword. And what's remarkable to me is how the areas of the brain like the hypothalamus and the amygdala, they're sort of like switches. I mean, there's context and there's gain control. You talked about the gain... |
Speaker B: Ambivalent one that is changing by the millisecond and mutually contradictory? No, that's absolutely the case. The prefrontal cortex. I more than once have regretted having, like, wasted 30 years of my life studying the hippocampus when I should have been studying the prefrontal cortex, because it's so much ... |
Speaker A: Amazing. It raises this question of cognitive flexibility. Can we tell ourselves that something is good for us even if we're not enjoying it? Can we wriggle around these corners of choosing the exercise or doing the. I personally am not a big fan of long bouts of meditation, but I've benefited tremendously f... |
Speaker B: An enormous amount. For example, being low in a hierarchy is generally bad for health, and like every mammal out there, including us, but we do something special, which is we can be part of multiple hierarchies at the same time. And while you may be low ranking in one of them, you could be extremely high ran... |
Speaker A: I love it. Your statement about the fact that we can select multiple hierarchies to participate in, to me, seems like a particularly important one nowadays with social media being so prevalent. I know you're not particularly active on social media, although you might be pleasantly or, I don't know, unpleasan... |
Speaker B: Well, I think what you get is in some ways the punchline of what's most human about humans, which is over and over. We use the exact same blueprint, the same hormones, the same kinases, the same receptors, the same everything. We're built out of the exact same stuff as all these other species out there. And ... |
Speaker A: Do you take steps in your own life to actively restrict the context in which you think and live and contemplate in order to enhance your creative life, your intellectual life? Are those steps that you actively take? |
Speaker B: Well, I very actively don't know how to make use of anything with social media, so I guess that counts as my having thus actively chosen not to learn how. So that's the case certainly for the last year and a half. Like lots of people, I've gone through stretches where I've managed to sort of enforce a morato... |
Speaker A: Well, I think there's a shifting trend towards trying to create a narrowing of context. And I like what I see. I have a niece, she's 14 years old, and she and her friends are very good at putting their phones away. They say, we're not going to have our phones for this interaction, especially after. And I rea... |
Speaker B: Well, my personal way out and left field inflammatory stance is I don't think we have a shred of free will. Despite, you know, 95% of philosophers and I think probably the majority of neuroscientists, saying that we have free will in at least some circumstances. I don't think there's any at all. And the reas... |
Speaker A: So I can appreciate that our behaviors and our choices are the consequence of a long line of dominoes that fell prior to that behavior. But is it possible that I can intervene in the domino effect, so to speak? You know, in other words, can my recognition of the fact that genes have heritability, there's an ... |
Speaker B: Nah. All of that can produce the wonderfully positive belief that change can happen, even dramatic change, even in the worst of circumstances, most unlikely people. And change can happen. Things can change. Don't be fatalistic. Don't decide, because we're mechanistic biological machines, that nothing can cha... |
Speaker A: So we can acknowledge that change is extremely hard to impossible, that circumstances can change, and yet that striving to be better human beings is still a worthwhile endeavor. Do I have that correct? |
Speaker B: Absolutely. Because simply the knowledge, either from experience or making it to the end of the right neurobiology class, has taught you that change can happen within a framework of a mechanistic neurobiology, you are now more open to being made optimistic by the good news in the world around you. You are mo... |
Speaker A: Yeah. As somebody who spent much of his career working on the hippocampus, I have to assume that you are a believer in neural plasticity, that neural circuits can change in response to, and that some of the same so called top down mechanisms of prefrontal cortex that we were talking about before can play a r... |
Speaker B: Yeah. And not only can, say, prenatal hormone exposure change the way your brain is being constructed, but learning that prenatal hormone exposure can change the construction of your brain will change your brain right now and how you think about where your intentions came from. Wow, maybe that had something ... |
Speaker A: That's such an important and powerful statement to hear. I think that many people think that if a tool doesn't involve a pill or a protocol, that it's useless. And certainly there are pills and protocols that are very useful in a variety of contexts for a variety of things. But the idea that knowledge itself... |
Speaker B: Yeah, it's going really slow. Title is determined a science of life without free will. And essentially the first half of the book is trying to convince a reader, okay, if not, that there's no free will whatsoever, but at least there's a lot less than is normally assumed. And I'm going through all the standar... |
Speaker A: Well, I speak for many, many people when I say that we're really excited for the book when it's done, and we will patiently wait a but with great excitement for the book. Determined, you said? Is the title correct? |
Speaker B: Yeah, determined. The science of life without free will. It seems like you can't publish a book these days without a subtitle. So that's it. |
Speaker A: Fantastic. Well, very excited to read the book. Very grateful to you for this conversation today. I learned a ton. Every time you speak, I learn. And for me, it's really been a pleasure and a delight to interact with you today and over the previous years, I should say, as colleagues. And thank you again, Rob... |
Speaker B: Thanks. And thanks for having me. This was a blast. |
Speaker A: Thank you for joining me for my conversation with Doctor Robert Sapolsky. If you're enjoying this podcast and learning from it, please subscribe to our YouTube channel. In addition, you can leave us comments and suggestions for future episodes and guests in the comment section on YouTube. Please also subscri... |
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