Dr. Robert Sapolsky: Science of Stress, Testosterone & Free Will

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.260 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman, and I'm a professor of neurobiology

00:00:11.960 | and ophthalmology at Stanford School of Medicine.

00:00:15.080 | Today, I have the pleasure of introducing

00:00:16.760 | Dr. Robert Sapolsky.

00:00:18.720 | Dr. Sapolsky is a professor of biology and neurosurgery

00:00:21.800 | at Stanford University.

00:00:23.680 | His laboratory has worked on a large variety of topics,

00:00:26.980 | including stress, hormones, including testosterone

00:00:30.560 | and estrogen, and how the different members

00:00:33.160 | of a given species interact according to factors

00:00:35.840 | like hormones, hierarchy within primate troops,

00:00:39.440 | and how things like stress, reproduction,

00:00:42.080 | and competition impact behavior.

00:00:45.380 | One of the things that makes Dr. Sapolsky's work so unique

00:00:48.480 | is that it combines elements from primatology,

00:00:51.000 | including field studies, with human behavior,

00:00:54.480 | in essence, trying to unveil how humans

00:00:57.640 | as old world primates are controlled by different elements

00:01:01.280 | of our biology, as well as our psychology.

00:01:03.880 | Dr. Sapolsky is also a prolific author of popular books,

00:01:07.840 | such as "Why Zebras Don't Get Ulcers,"

00:01:09.980 | "The Trouble with Testosterone,"

00:01:11.680 | and "Behave the Biology of Humans at Our Best and Worst."

00:01:15.440 | During the course of our discussion today,

00:01:17.280 | Robert also revealed to me that he is close

00:01:19.120 | to completing a new book entitled

00:01:21.360 | "Determined, the Science of Life Without Free Will."

00:01:24.960 | And indeed, we discuss the science of life

00:01:27.200 | without free will during this episode.

00:01:29.820 | We also discuss stress and how best to control stress

00:01:33.320 | and how stress controls us

00:01:35.280 | at both conscious and subconscious levels.

00:01:38.060 | We talk about testosterone and estrogen

00:01:40.560 | and hormone replacement therapy

00:01:42.520 | and how those impact our mind, our psychology,

00:01:45.320 | and our interactions with others.

00:01:47.520 | As with any discussion with Dr. Sapolsky,

00:01:49.700 | we learn about scientific mechanisms

00:01:51.480 | that make us who we are.

00:01:53.040 | And today we also discuss tools

00:01:54.880 | and how we can leverage those scientific mechanisms

00:01:57.300 | in order to be better versions of ourselves.

00:02:00.360 | I should mention that unlike most guest interviews

00:02:02.520 | on the Huberman Lab Podcast,

00:02:04.540 | this one had to be carried out remotely

00:02:06.240 | due to various constraints.

00:02:07.600 | So you may hear the occasional audio artifact.

00:02:10.660 | Please excuse that.

00:02:11.620 | We felt that the value of a conversation with Dr. Sapolsky

00:02:14.920 | was well worth those minor, minor glitches.

00:02:18.340 | And indeed, the information that he delivers us

00:02:20.880 | is tremendously valuable, interesting,

00:02:23.600 | and in many cases, actionable as well.

00:02:25.840 | Before we begin, I'd like to emphasize that this podcast

00:02:28.400 | is separate from my teaching and research roles at Stanford.

00:02:31.420 | It is, however, part of my desire and effort

00:02:33.600 | to bring zero cost to consumer information about science

00:02:36.340 | and science-related tools to the general public.

00:02:39.200 | In keeping with that theme,

00:02:40.320 | I'd like to thank the sponsors of today's podcast.

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00:03:40.060 | Today's podcast is also brought to us by Inside Tracker.

00:03:43.560 | Inside Tracker is a personalized nutrition platform

00:03:46.020 | that analyzes data from your blood and DNA

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00:06:24.060 | And now without further ado,

00:06:26.260 | my conversation with Dr. Robert Sapolsky.

00:06:29.380 | Great, well, thank you so much, Robert,

00:06:30.940 | for joining us today.

00:06:33.000 | I've been looking forward to this for a very long time.

00:06:36.020 | I appreciate it.

00:06:36.860 | - Glad to be here.

00:06:39.720 | There's an enormous range of topics

00:06:42.200 | that we could drill into,

00:06:44.340 | but just to start off,

00:06:46.940 | I want to return to a topic that is near and dear

00:06:50.140 | to your heart, which is stress.

00:06:52.340 | And one of the questions that I get most commonly is,

00:06:57.180 | what is the difference between short and long-term stress

00:07:00.700 | in terms of their benefits and their drawbacks?

00:07:05.140 | And the reason I say benefits is that obviously stress

00:07:08.720 | and the stress response can keep us alive,

00:07:10.660 | but stress of course can also sharpen our mental acuity

00:07:14.460 | and things of that sort.

00:07:15.820 | So how should we conceptualize stress

00:07:19.600 | and how should we conceptualize stress

00:07:22.040 | in the short-term and in the long-term?

00:07:24.520 | - Well, basically sort of two graphs that one would draw.

00:07:29.520 | The first one is just all sorts of beneficial effects

00:07:34.620 | of stress short-term.

00:07:36.940 | And then once we get into the chronicity,

00:07:39.660 | it's just downhill from there.

00:07:41.540 | Short-term because it saves you from the predator.

00:07:45.140 | Short-term because you're giving a presentation

00:07:47.980 | and you think more clearly or your focus is better,

00:07:52.220 | all sorts of aspects of that.

00:07:53.920 | And what then winds up being an argument

00:07:57.540 | is how long does it take to go from short-term to long-term?

00:08:02.360 | And that's somewhat arbitrary,

00:08:05.240 | but the sorts of chronic stressors

00:08:07.980 | that most people deal with

00:08:09.780 | are just undeniably in the chronic range,

00:08:13.200 | like having spent the last 20 years,

00:08:15.300 | daily traffic jams or abusive boss or some such thing.

00:08:20.160 | The other curve that's sort of perpendicular to this

00:08:24.660 | is dealing with the fact

00:08:26.760 | that sometimes stress is a great thing.

00:08:30.400 | Like our goal is not to cure people of stress

00:08:34.880 | because if it's the right kind, we love it.

00:08:36.960 | We pay good money to be stressed that way

00:08:40.460 | by a scary movie or rollercoaster ride.

00:08:43.980 | What you wind up seeing is

00:08:45.920 | when it's the right amount of stress,

00:08:48.300 | it's what we call stimulation.

00:08:50.620 | And the basic curve there is

00:08:52.900 | here's an optimal level of stimulation and too little,

00:08:56.820 | and function goes down with what we would call boredom,

00:09:00.100 | and too much and function goes down

00:09:02.120 | with what we would call stress.

00:09:04.100 | And the optimum is what all of us aim for.

00:09:08.900 | - In terms of the benefits of stress in the short term,

00:09:13.820 | one thing that's really striking to me is

00:09:17.860 | how physiologically the stress response

00:09:22.320 | looks so much like the excitement response

00:09:25.100 | to a positive event.

00:09:27.400 | And we can speculate that the fundamental difference

00:09:31.460 | between short-term stress and short-term excitement

00:09:35.220 | is some neuromodulator like dopamine or something like that.

00:09:38.940 | But is there anything else that we know about the biology

00:09:42.340 | that reveals to us what really creates

00:09:46.020 | this thing we call valence,

00:09:47.260 | that an experience can be terrible or feel awful,

00:09:51.680 | or it can feel wonderful, exhilarating,

00:09:54.720 | depending on this somewhat subjective feature

00:09:58.340 | we call valence.

00:10:00.020 | Do we know what valence is or where it resides?

00:10:03.200 | - On a really mechanical level,

00:10:07.220 | if you're in a circumstance that is requiring

00:10:11.700 | that your heart races and you're breathing as fast

00:10:16.020 | and you're using your muscles and some such thing,

00:10:19.620 | you're going to be having roughly

00:10:21.740 | the same brain activation profile,

00:10:24.780 | whether this is for something wonderful

00:10:26.420 | or something terrible,

00:10:27.820 | with the one exception being that if the amygdala

00:10:31.220 | is part of the activation,

00:10:33.460 | this is something that's going to be counting as adverse.

00:10:36.300 | Whether that's the circumstance, an adverse circumstance,

00:10:41.420 | recruiting the amygdala into it

00:10:43.540 | and how much it's the amygdala being involved

00:10:46.700 | biases you towards interpreting it as even more awful.

00:10:50.820 | The amygdala in some ways is kind of the checkpoint

00:10:54.180 | as to whether we're talking about excitement

00:10:57.100 | or terror.

00:10:58.420 | - Let's use the amygdala as a transition point

00:11:02.140 | to another topic that you've spent many years working on

00:11:06.500 | and thinking about,

00:11:07.620 | which is testosterone and other sex steroid hormones.

00:11:12.260 | I heard you say once before that

00:11:14.600 | among all the brain areas that bind testosterone,

00:11:19.980 | that where testosterone can park and create effects,

00:11:23.220 | that the amygdala is among the most chock-a-block full

00:11:28.220 | of these parking spots, these receptors.

00:11:32.060 | I realize there's a lot here,

00:11:34.180 | but how should we think about the role of testosterone

00:11:37.700 | in the amygdala given that the engagement of the amygdala

00:11:41.240 | is fundamental in this transition point

00:11:43.420 | between a exhilarating positive response

00:11:46.260 | and a negative stressful response?

00:11:50.020 | Or maybe just broadly,

00:11:51.500 | how should we think about testosterone

00:11:53.220 | and its effects on the brain?

00:11:54.660 | - And pertinent to the transition

00:11:58.260 | from whether this is a stressor that's evoking fear

00:12:02.220 | or evoking aggression in terms of that continuum also,

00:12:06.380 | 'cause the amygdala is in the center

00:12:08.460 | of all four points on those axes.

00:12:11.460 | Basically, almost everybody out there

00:12:15.540 | has a completely wrong idea as to what testosterone does,

00:12:19.140 | which is testosterone makes you aggressive

00:12:21.900 | because males, virtually every species out there,

00:12:24.780 | have more testosterone and are more aggressive,

00:12:27.260 | and seasonal maters have testosterone

00:12:30.380 | surging at the time of year.

00:12:32.020 | They're punching it out over territory.

00:12:35.060 | And you take testosterone out of the picture.

00:12:39.200 | You castrate any mammal out there, including us,

00:12:43.060 | and levels of aggression will go down.

00:12:45.860 | And the easy thing then is to conclude

00:12:48.740 | that testosterone causes aggression.

00:12:51.900 | And the reality is testosterone does no such thing.

00:12:55.280 | It doesn't cause aggression.

00:12:57.180 | And you can see this both behaviorally and in the amygdala.

00:13:00.640 | What does testosterone do?

00:13:02.940 | It lowers the threshold for the sort of things

00:13:06.440 | that would normally provoke you into being aggressive

00:13:09.620 | so that it happens more easily.

00:13:12.040 | It makes systems that are already turned on

00:13:16.220 | turn on louder rather than turning on aggressive music

00:13:20.580 | or some such thing.

00:13:21.620 | What does that look like behaviorally?

00:13:24.240 | You take five male monkeys, put them together.

00:13:27.480 | They form a dominance hierarchy.

00:13:30.060 | Number one is great.

00:13:31.260 | Number five is miserable.

00:13:32.700 | Number three is right in between.

00:13:34.220 | Now take number three and shoot the guy up

00:13:37.340 | with tons of testosterone,

00:13:39.920 | and he's going to be involved in more fights.

00:13:43.020 | Aha, testosterone uniformly causes aggression.

00:13:46.740 | But you look closely and there's a pattern to it.

00:13:49.660 | Is number three now challenging numbers two and one

00:13:54.260 | for their place in the hierarchy?

00:13:55.780 | Absolutely not.

00:13:56.820 | He is brown nosing them exactly as much as he used to.

00:14:00.540 | What's going on is he's just a miserable terror

00:14:03.700 | to poor number four and five.

00:14:06.220 | And in that case, what testosterone is doing

00:14:08.760 | is amplifying the preexisting patterns of aggression,

00:14:13.560 | amplifying the social learning that's already gone into it.

00:14:17.900 | Now on sort of the more reductive level,

00:14:20.780 | so how does that translate into the amygdala?

00:14:23.440 | Does testosterone make amygdaloid neurons

00:14:26.840 | have action potentials?

00:14:28.900 | Does it cause those neurons to suddenly speak

00:14:32.320 | about fear and aggression spontaneously?

00:14:35.040 | Absolutely not.

00:14:36.540 | What they do is if the amygdala is already being stimulated,

00:14:41.540 | it increases the rate of neuronal firing.

00:14:44.400 | What it's worth, it shortens after hyperpolarizations.

00:14:49.620 | So the theme there exactly is it's not creating aggression,

00:14:53.260 | it's just upping the volume

00:14:54.900 | of whatever aggression is already there.

00:14:57.660 | And once you factor that in,

00:14:59.860 | it's impossible to say anything about what testosterone does

00:15:04.940 | outside the context of what testosterone-related behaviors,

00:15:09.940 | how they get treated in your social settings.

00:15:14.260 | - Yeah, and in terms of status

00:15:17.840 | and the relationship between individuals,

00:15:19.840 | either non-human primates or humans,

00:15:23.120 | can we say that testosterone and levels of testosterone,

00:15:26.820 | or I should say, can we say that relative levels

00:15:29.420 | of testosterone between individuals

00:15:31.620 | is correlated to status within the hierarchy?

00:15:34.980 | - Yes, but in a way that winds up

00:15:38.600 | being totally uninteresting.

00:15:41.020 | Like you go back, I don't know,

00:15:42.480 | whatever number of decades to endocrinology texts,

00:15:45.620 | and there were two totally reliable findings in there.

00:15:49.540 | Let's see, I have a dog in here that's so good.

00:15:51.740 | - Oh good, we like dogs at the Huberman Lab podcast.

00:15:54.500 | - Okay, he's jingling a bit.

00:15:57.460 | - They are welcome, they are absolutely welcome, yeah.

00:16:00.180 | And there'd be two truisms,

00:16:02.900 | which is higher levels of testosterone

00:16:06.220 | predict higher levels of aggression

00:16:08.680 | in humans and other animals.

00:16:10.300 | Higher levels of testosterone

00:16:12.460 | predict higher levels of sexual activity.

00:16:15.580 | Whoa, testosterone causing both.

00:16:18.420 | And the correlation is there.

00:16:20.340 | And when you look closely, we've got cause and effect stuff.

00:16:23.780 | Sexual behavior raises testosterone levels.

00:16:27.380 | Aggression raises testosterone levels.

00:16:30.400 | Your levels beforehand are barely predictive

00:16:33.300 | of what's gonna happen.

00:16:34.820 | So it's a response rather than a cause.

00:16:37.140 | When you look at that though,

00:16:39.840 | in terms of making sense of individual differences,

00:16:42.820 | they don't matter a whole lot.

00:16:45.700 | You can like spend an entire career

00:16:50.140 | on the social circumstances that produced

00:16:53.060 | three and a half percent more testosterone in the circulation

00:16:57.700 | and expect to see all sorts of interesting implications.

00:17:02.020 | And that's not really the case.

00:17:04.240 | It's somewhat of a yes or no modulator

00:17:07.980 | of a much more subtle social stuff that's already there.

00:17:12.200 | - Very interesting.

00:17:13.580 | You know, I think that there are a lot of misconceptions

00:17:17.660 | about human biology, but testosterone seems to be one area

00:17:21.340 | where at least from what I can find on the internet,

00:17:24.420 | there's a sort of at the peak of misunderstanding.

00:17:28.960 | Maybe we could just ask a few more questions

00:17:30.520 | about testosterone and sexual behavior,

00:17:32.320 | because there's an interesting story there

00:17:34.720 | about castration versus non-castration

00:17:37.980 | and the causality again.

00:17:40.260 | But before you address that,

00:17:42.360 | I just want to highlight something that you said

00:17:44.140 | that I think is so vital, which is that behaviors

00:17:47.900 | such as aggressive behaviors and sexual behaviors

00:17:50.380 | can actually increase testosterone.

00:17:52.260 | Did I hear that correctly?

00:17:53.820 | And the reverse is sort of true, but not in a causal way.

00:17:58.820 | Is that right?

00:18:00.460 | - The opposite direction with the causality, yeah.

00:18:04.300 | - Yeah, so if I were to increase somebody's testosterone

00:18:07.020 | by 30% male or female, doesn't matter,

00:18:10.180 | their sexual behavior may or may not change.

00:18:12.740 | - Essentially zero effect at all.

00:18:15.240 | Your brain is not that sensitive to fluctuations

00:18:18.600 | in testosterone levels.

00:18:20.360 | In terms of things like aggression,

00:18:22.120 | raising testosterone just is a great footnote.

00:18:25.260 | If you have the right type of willing to die

00:18:29.200 | in the trenches devotion sort of thing,

00:18:31.680 | watching your favorite team play a sport

00:18:34.720 | will raise your testosterone levels

00:18:37.000 | as you sit there with a potato chips in your arm chair.

00:18:39.920 | So it's not the physicality of aggression,

00:18:43.540 | it's the psychological framing of it.

00:18:47.780 | So yeah, testosterone is not causing that.

00:18:51.440 | And a great way to appreciate that is,

00:18:54.840 | okay, so you had all these

00:18:57.560 | testosterone sexual behavior correlations

00:19:00.360 | and you do the definitive endocrine intervention,

00:19:04.760 | which is you do a subtraction study,

00:19:08.000 | you've removed the testes, and as I said before,

00:19:11.360 | levels of sexual behavior goes down.

00:19:14.260 | Good, we've just shown that testosterone

00:19:16.360 | is somehow causative.

00:19:18.220 | Critically, they go down, but not down to zero,

00:19:22.440 | whether you are a rat or a monkey or a human, whatever.

00:19:27.440 | And what predicts how much residual sexual behavior is there,

00:19:31.880 | how much sexual behavior there was before castration.

00:19:35.640 | What that's telling you is by then,

00:19:39.640 | that's behavior that's being carried by social learning

00:19:43.060 | in context, rather than by a hormone, exact same thing

00:19:47.080 | with aggression, drops after castration, doesn't go to zero.

00:19:51.120 | The more prior history of it,

00:19:53.280 | the more it just keeps coasting along on its own,

00:19:55.740 | even without testosterone.

00:19:57.880 | - Very interesting, can we say that there's an exception

00:20:01.420 | in terms of the early organizing effects of hormones?

00:20:04.560 | Like for instance, if a developing animal is deprived

00:20:07.040 | of testosterone or estrogen or aromatized testosterone

00:20:11.500 | into estrogen, there's a whole story there as you know,

00:20:13.840 | but then I could imagine that the circuits of the brain

00:20:17.160 | that are responsible for initiating sexual behavior

00:20:19.500 | in the first place might not emerge

00:20:21.240 | and therefore not be sensitive to testosterone later in life.

00:20:24.560 | Is that right?

00:20:25.400 | - Yeah, exactly, and a great way of seeing that

00:20:29.000 | is this totally nutty biological factoid,

00:20:33.360 | which is the second to fourth digit ratio in hands.

00:20:37.840 | - Oh yeah.

00:20:38.680 | - Totally obscure thing, the ratio of one to the other

00:20:42.220 | in some way reflects levels of testosterone androgen

00:20:46.740 | exposure during fetal life.

00:20:48.820 | And I can't remember which way it goes and it's minuscule

00:20:51.980 | and you need a thousand people in your sample size

00:20:54.680 | to be able to see anything,

00:20:56.100 | but you see it in other primates, it's already there

00:20:59.920 | and fetal, sonograms, all of that.

00:21:03.020 | So that's a readout of subtle differences

00:21:07.740 | in prenatal exposure and that winds up being a predictor

00:21:11.960 | of a whole range of subtle stuff in adult behavior.

00:21:16.760 | So yeah, at the fetal end,

00:21:18.100 | when you're still building everything,

00:21:19.800 | testosterone and the amount of it

00:21:21.540 | is making a huge difference.

00:21:23.240 | By the time you're an adult,

00:21:25.060 | it's just somewhat of an all or none signal.

00:21:29.340 | - Yeah, I have a confession,

00:21:31.260 | which is that I was a master's student at Berkeley

00:21:33.380 | in Mark Breedlove's arena.

00:21:35.660 | So I'm an author on that paper,

00:21:38.400 | although I'm deep within the author line

00:21:40.300 | and you got the description of it exactly right,

00:21:43.020 | that it's the D2, the index finger to the ring finger ratio

00:21:46.540 | is more similar in females and then it is in males.

00:21:50.180 | In males, the index finger tends to be shorter.

00:21:52.140 | And for people out there who are listening to this,

00:21:53.860 | who are now freaking out or measuring,

00:21:57.720 | there's a proper way to measure this,

00:21:59.420 | which is eyeballing it doesn't work all the time

00:22:03.360 | unless at the extremes.

00:22:04.540 | And there's some more interesting stories there.

00:22:06.460 | It actually has been replicated no fewer than five times,

00:22:10.460 | Mark Breedlove tells me.

00:22:12.180 | But yes, in terms of these early organizing effects,

00:22:17.320 | those seem very robust in most studies.

00:22:20.720 | These later effects are a sort of activation

00:22:23.500 | of neural circuits by hormones.

00:22:25.060 | I'm absolutely fascinated by this.

00:22:27.300 | And I do have a couple other questions,

00:22:30.160 | which is we normally associate testosterone with males,

00:22:33.680 | but of course, females make testosterone as well

00:22:36.620 | from the adrenals and presumably elsewhere too.

00:22:39.140 | I'm guessing if we looked hard enough,

00:22:40.540 | we'd probably find that there were other sources

00:22:42.120 | of androgens in females.

00:22:45.040 | Can we say that these general contours of effects

00:22:48.940 | on aggression also pertain to females?

00:22:53.540 | And I suppose I should ask in particular

00:22:57.100 | about female-female aggression,

00:22:59.540 | which does exist in many species,

00:23:01.260 | female-male aggression, as well as maternal aggression,

00:23:04.180 | which is a robust aspect of our evolution, of course,

00:23:08.420 | that the mother will, an angry mother animal of any kind

00:23:13.160 | protecting her young is truly dangerous

00:23:16.540 | in the best sense of the word.

00:23:19.100 | - And that type of post-parturition period

00:23:22.880 | after birth aggression is all about estrogen,

00:23:27.760 | progesterone, those sorts of things.

00:23:29.740 | Female aggression the rest of the time

00:23:31.740 | has testosterone as a major player

00:23:34.660 | at a much lower level on the average,

00:23:37.580 | on the average, one always has to say,

00:23:40.420 | but it's basically the same punchlines.

00:23:42.740 | In females, the lower levels of testosterone

00:23:45.900 | are essential for typical levels of aggression

00:23:49.420 | and sexual behavior.

00:23:51.060 | None of us, they're not causing it.

00:23:53.000 | It's not sensitive to small individual differences.

00:23:55.920 | Same exact thing.

00:23:57.260 | You can get way over impressed

00:23:59.780 | with the importance of androgens in females

00:24:02.700 | just as readily as in males.

00:24:05.120 | - So in line with that,

00:24:06.780 | how should we conceptualize testosterone?

00:24:09.820 | I mean, I realize there isn't a single sentence

00:24:11.940 | or that can capture a hormone and all its effects

00:24:16.340 | because hormones have so many different slow

00:24:18.180 | and fast effects on the brain, on other glands,

00:24:20.300 | on their own, on the very glands that produce them.

00:24:23.340 | But as I've heard you talk about testosterone today

00:24:25.960 | and over the years, I start to get the impression

00:24:28.320 | that as the most misunderstood molecule

00:24:31.940 | in human health in the universe,

00:24:34.120 | it's clearly doing something very powerful.

00:24:37.700 | It's shifting the way that certain neural circuits work,

00:24:40.540 | adjusting the gain on the amygdala, as you described,

00:24:42.820 | and certainly other things as well.

00:24:45.380 | Is there any truism about testosterone

00:24:49.560 | and its relationship to effort

00:24:51.460 | or its relationship to resilience

00:24:55.300 | and in a way that maybe will help me and other people

00:24:59.400 | sort of think about how to think about testosterone?

00:25:03.120 | - Yeah, maybe three separate answers to that.

00:25:08.040 | The first one is I think it's a fair summary

00:25:11.640 | to think that when it comes to motivated strong behaviors,

00:25:16.640 | what testosterone does is make you more

00:25:19.400 | of whatever you already are in that domain.

00:25:22.720 | Sexual arousal, libido, aggressiveness,

00:25:27.000 | spontaneous aggression, reactive aggression,

00:25:29.780 | things of that sort.

00:25:30.940 | It's upping the volume of things

00:25:32.540 | that are already strongly there.

00:25:34.140 | Second way to think about it is,

00:25:39.100 | well, here's like my favorite finding about testosterone.

00:25:44.960 | And this was some wonderful work by a guy, John Wingfield,

00:25:49.540 | who's one of the best behavioral endocrinologists out there.

00:25:52.960 | And about 20 years ago, he formulated what was called

00:25:56.880 | the challenge hypothesis of testosterone action.

00:26:01.600 | What does testosterone do?

00:26:03.760 | Testosterone is what you secrete

00:26:06.320 | when your status is being challenged.

00:26:08.980 | And it makes it more likely that you'll do the behaviors

00:26:11.760 | needed to hold onto your status.

00:26:14.280 | Okay, so that's totally boringly straightforward

00:26:16.960 | if you're a baboon.

00:26:18.200 | If somebody is challenging your high rank,

00:26:21.020 | the appropriate response on your part

00:26:22.700 | is going to be aggression.

00:26:24.440 | All right, so we've just gotten through the back door

00:26:26.760 | to testosterone and aggression again.

00:26:28.820 | But then you get to humans.

00:26:31.680 | And humans have lots of different ways

00:26:33.720 | of achieving or maintaining status.

00:26:36.320 | And all you need to do is go to like some fancy

00:26:39.620 | private school's annual auction,

00:26:42.720 | and you will see all these half-drunk alpha males

00:26:46.320 | competing to see who can give the most money away

00:26:50.720 | as a show of conspicuous like, you know,

00:26:54.120 | property that they have.

00:26:56.480 | And in a setting like that, I mean,

00:26:58.800 | I haven't been able to take urine samples

00:27:01.680 | at those times, unfortunately,

00:27:03.300 | but that shows the flip side of it.

00:27:05.880 | If you have a species that hands out status

00:27:08.680 | in a very different sort of way,

00:27:10.960 | testosterone is going to boost that also.

00:27:12.720 | Okay, so that generates a totally nutty prediction.

00:27:15.960 | Wow, take people in a circumstance,

00:27:18.760 | say playing an economic game,

00:27:20.960 | where you get status by being trustworthy

00:27:24.600 | and being generous in your interactions with the game.

00:27:27.660 | If you give people testosterone,

00:27:29.840 | does that make them more generous?

00:27:32.240 | And that's absolutely the case.

00:27:34.240 | Totally cool finding.

00:27:35.980 | Showing you, I don't know,

00:27:38.600 | basically if you took a whole bunch of Buddhist monks

00:27:41.960 | and shot them up with testosterone,

00:27:44.240 | they'd get all competitive with each other

00:27:46.120 | as to who could do the most random acts of kindness.

00:27:49.440 | And if we have a societal problem with too much aggression,

00:27:54.440 | the first culprit to look at is not testosterone.

00:27:57.440 | The first to look at is that we hand out

00:28:00.120 | so much damn elevated status for aggression

00:28:03.480 | in so many circumstances.

00:28:06.000 | So I find that finding to be fantastic.

00:28:09.600 | Third thing about subtlety of testosterone.

00:28:11.960 | Okay, so like some subtler behavioral effects,

00:28:15.240 | you give testosterone to people

00:28:17.320 | and they become more confident.

00:28:19.840 | They become more self-confident.

00:28:22.400 | Well, that's good.

00:28:23.440 | People pay to take all sorts of nonsensical self-help courses

00:28:27.620 | that will boost your self-esteem.

00:28:29.920 | And that's a good thing.

00:28:31.680 | Unless testosterone makes you more confident,

00:28:35.640 | that is inaccurate.

00:28:37.420 | And you're more likely to barrel into wrong decisions.

00:28:41.040 | What's shown in economic gameplay

00:28:44.040 | is that testosterone, by making you more confident,

00:28:47.040 | makes you less cooperative.

00:28:48.960 | Because who needs to cooperate?

00:28:50.360 | Because I'm on top of this all on my own.

00:28:52.580 | Testosterone makes people cocky and impulsive.

00:28:57.600 | And that may be great in one setting,

00:28:59.920 | but if in the other is you're absolutely sure

00:29:02.240 | your army is gonna overrun the other country in three days.

00:29:05.680 | So hell, let's start World War I

00:29:07.560 | and you get a big surprise out of it.

00:29:09.800 | Testosterone altering risk assessment beforehand

00:29:13.640 | probably played a big role in that kind of miscalculation.

00:29:17.720 | - Super interesting.

00:29:19.080 | I always think about testosterone and dopamine

00:29:21.480 | being close cousins in the brain,

00:29:23.680 | not just because of their relationship

00:29:25.680 | through the pituitary and hypothalamus, that of course,

00:29:28.760 | but also because of dopamine's salient role

00:29:32.920 | in creating this bias towards exteroception.

00:29:37.240 | When somebody takes a drug that increases dopamine

00:29:40.840 | or they're chock-a-block full of dopamine,

00:29:43.280 | they tend, I want to highlight tend

00:29:45.680 | 'cause I'm really generalizing it,

00:29:47.020 | but they tend to focus on outward goals,

00:29:49.920 | things beyond the boundaries of their skin.

00:29:52.740 | And testosterone seems to do a bit of the same.

00:29:56.200 | It tends to put us into a similar mode

00:29:58.200 | of perceiving the outside world

00:30:01.120 | in ways that we're asking questions like,

00:30:04.760 | how do I relate to this other of my species?

00:30:07.800 | How do I relate to these goals?

00:30:09.740 | Is there anything that we can do

00:30:12.600 | to better conceptualize the relationship

00:30:14.560 | between testosterone and dopamine and motivation?

00:30:17.680 | Or would that just take us down the alleyways

00:30:20.840 | of neural pathways and the hypothalamus, which was fine too.

00:30:24.780 | - Well, I think it's got lots to do

00:30:27.300 | with sort of this massive revisionism about dopamine.

00:30:30.960 | Everyone since the pharaohs got brought up

00:30:33.920 | being taught that dopamine is about pleasure and reward.

00:30:37.480 | It turns out it isn't.

00:30:38.480 | It's about anticipation of reward.

00:30:41.560 | And it's about generating the motivation,

00:30:44.080 | the goal-directed behavior needed to go get that reward.

00:30:48.040 | And before you know it,

00:30:49.080 | you're using like elevated dopamine your entire life

00:30:53.080 | to motivate you to do whatever's going to get you

00:30:55.760 | like entry into heaven after life.

00:30:58.240 | Kind of, you know, it's doing that sort of thing.

00:31:01.920 | So it's really about the motivation.

00:31:04.600 | And what testosterone does,

00:31:06.520 | even in individuals who are not aggressive

00:31:09.160 | and why testosterone replacement

00:31:11.360 | is often a very helpful thing for aging males,

00:31:14.600 | is it increases energy.

00:31:16.720 | It increases a sense of there-ness,

00:31:21.120 | of presence, of alertness.

00:31:22.680 | It increases motivation.

00:31:24.360 | So that's a whole aspect which then takes us into

00:31:28.460 | is your motivation to get up and like go, you know,

00:31:33.460 | hand out lots of soup in a soup kitchen for homeless people?

00:31:37.300 | Or is it to get up and go ethnically cleanse a village?

00:31:41.100 | It's got much to do with what your makeup was

00:31:45.060 | before the testosterone got on board.

00:31:47.500 | So it's activating in an energetic sense.

00:31:50.700 | Testosterone within minutes

00:31:53.160 | increases glucose uptake into skeletal muscle.

00:31:56.700 | You're just more awake and alert and all of that.

00:32:00.420 | And that has a lot to do with what dopamine does.

00:32:03.120 | And as one might predict then,

00:32:05.260 | getting just the right levels of testosterone

00:32:09.300 | infused into your bloodstream feels great to lab rats.

00:32:13.740 | They will lever press to get infused into the range

00:32:17.920 | that optimizes dopamine release.

00:32:19.960 | So there's, you're absolutely right.

00:32:21.960 | You're deeply intertwined.

00:32:24.460 | - Yeah, such beautiful biology there.

00:32:26.540 | And I love the way you encapsulate their relationship.

00:32:29.280 | I want to ask about estrogen.

00:32:32.360 | We don't hear about estrogen as often.

00:32:36.340 | And it's always interesting to me now

00:32:38.500 | doing some public facing education, you know,

00:32:41.100 | that testosterone is this very controversial molecule.

00:32:44.600 | Just to say it is almost controversial.

00:32:47.300 | But estrogen doesn't seem to hold

00:32:50.420 | the same controversial weight.

00:32:53.540 | And yet estrogen has some very powerful effects

00:32:56.660 | on both the animal brain and on the human brain

00:32:59.660 | of males and females.

00:33:02.080 | Men do not want their estrogen to go too low.

00:33:05.900 | Terrible things happen.

00:33:07.020 | They will lose cognitive function.

00:33:08.980 | Libido can drop.

00:33:10.940 | So men need estrogen as well.

00:33:12.640 | But perhaps maybe we can put the same filter on estrogen

00:33:17.300 | as we did on testosterone.

00:33:19.420 | Are there any general themes of estrogen

00:33:21.920 | that people should be aware of

00:33:24.760 | or that you think that are generally misunderstood?

00:33:27.660 | Is it really all about feelings and empathy

00:33:30.060 | and making us more sensitive?

00:33:31.360 | I sense not.

00:33:34.260 | - No, and it's once again, very context dependent.

00:33:38.020 | And if estrogen after giving birth

00:33:41.220 | is playing a central role in you wanting to shred the face

00:33:44.340 | of somebody getting too close to your kittens kind of thing,

00:33:48.340 | we know it's not just warm, fuzzy, empathic kind of stuff.

00:33:53.340 | Estrogen in lots of ways could be summarized

00:33:58.100 | by if you had a choice in the matter

00:34:00.240 | between having a lot of estrogen in your bloodstream or not,

00:34:03.340 | go for having a lot of estrogen.

00:34:05.700 | It enhances cognition exactly as you said.

00:34:10.000 | It stimulates neurogenesis in the hippocampus.

00:34:13.560 | It increases glucose and oxygen delivery.

00:34:16.980 | It protects you from dementia.

00:34:19.660 | It decreases inflammatory oxidative damage to blood vessels,

00:34:24.660 | which is why it's good for protecting

00:34:26.500 | from cardiovascular disease in contrast to testosterone,

00:34:30.460 | which is making every one of those things worse.

00:34:33.220 | This brings up this minefield of the question,

00:34:38.180 | which is so what about post-menopausal estrogen?

00:34:41.480 | And all sorts of lab studies with non-human primates

00:34:46.380 | suggested that you keep estrogen levels high

00:34:50.460 | after a monkey's equivalent of menopause

00:34:53.060 | and you're gonna keep brain health a lot better,

00:34:56.260 | decreasing the risk of dementia, stroke, every such thing.

00:35:00.980 | Estrogen is a great antioxidant, all of that.

00:35:03.900 | So in the '90s, I think when Healy, I'm forgetting her name,

00:35:08.900 | but when there was the first female head of the NIH,

00:35:15.580 | Bernadette Healy, set up this massive prospective

00:35:20.580 | human study, what was gonna be the biggest one of all times,

00:35:25.100 | looking at the pluses and minuses

00:35:27.420 | of post-menopausal estrogen.

00:35:29.700 | And tens of thousands of women, this was great,

00:35:33.380 | and they had to cut the study short

00:35:36.540 | because what they were seeing was estrogen

00:35:39.380 | was not only doing the normal bad stuff that you expect

00:35:42.860 | in terms of some decalcification stuff,

00:35:46.260 | but it was increasing the risk of cardiovascular disease.

00:35:49.900 | And it was increasing the risk of stroke

00:35:51.740 | and it was increasing the risk of dementia.

00:35:54.260 | And this ground to a halt and everybody,

00:35:57.220 | they stopped the study in front page news

00:35:59.820 | and everybody had that point.

00:36:02.380 | And nobody could make sense of it

00:36:04.740 | who had been spending the last 20 years

00:36:06.700 | studying the exact same thing in primates

00:36:08.900 | and seeing all the protective effects.

00:36:11.380 | And the explanation turned out to be one of those things

00:36:16.380 | where like law of unexpected consequences.

00:36:20.340 | Okay, menopause in women last different lengths of time.

00:36:24.660 | That may be a factor that's gonna come.

00:36:26.700 | You know what?

00:36:27.780 | Let's not start giving our study subjects more estrogen

00:36:31.340 | until they're totally past menopause.

00:36:34.260 | And when you've got that lag time in between,

00:36:38.180 | you shift all sorts of estrogen receptor patterns

00:36:41.500 | and that's where all of the bad effects come from.

00:36:44.500 | All of the monkey studies had involved

00:36:46.980 | just maintaining ovulatory levels

00:36:50.900 | into the post-menopausal period.

00:36:53.340 | And you do that and you get great effects.

00:36:55.260 | Estrogen is one of the greatest predictors

00:36:57.700 | of protection from Alzheimer's disease, all of that,

00:37:00.660 | but it needs to be physiological.

00:37:04.220 | Just keep continuing what your body has been doing

00:37:08.100 | for a long time versus let the whole thing shut down

00:37:11.700 | and suddenly like try to fire up the coal stoves

00:37:15.000 | at the bottom of the basement kind of thing

00:37:16.940 | and get that going.

00:37:18.540 | There you get utterly different outcomes.

00:37:21.100 | And that caused a lot of human health consequences

00:37:25.340 | when people suddenly decided that estrogen

00:37:28.540 | is in fact neurologically endangering post-menopausal aid.

00:37:33.540 | - Wow, that's fascinating.

00:37:35.380 | And I never thought that these steroid hormone receptors

00:37:39.060 | could, you know, by not binding estrogen,

00:37:42.380 | being devoid of estrogen binding, I should say,

00:37:44.940 | could then set off opposite biochemical cascades.

00:37:49.080 | Fascinating.

00:37:49.920 | I guess it raises the question

00:37:50.840 | about testosterone replacement too,

00:37:52.500 | whether or not people should talk to their doctor

00:37:56.280 | before too long.

00:37:58.920 | Men and women talk to your physicians before too long

00:38:01.940 | to avoid these, whatever is happening in these periods

00:38:05.180 | where there isn't sufficient testosterone and/or estrogen.

00:38:08.980 | Sounds like it could cause longer-term problems

00:38:11.820 | even when therapies are introduced.

00:38:14.580 | - Two additional misery/complications.

00:38:18.700 | So, okay, you're trying to understand,

00:38:20.360 | you look at women with a history

00:38:22.500 | with or without post-menopausal estrogen replacement,

00:38:25.580 | where it's done right, and you're seeing 20 years later,

00:38:30.500 | estrogen is a predictor of a decreased risk of Alzheimer's.

00:38:33.780 | Then you gotta start trying to do

00:38:36.500 | the unpacking prospective type studies.

00:38:40.340 | How much estrogen?

00:38:42.200 | At which times?

00:38:44.100 | Estrogen is just a catch-all term for a bunch of hormones.

00:38:49.100 | Estrone, estradiol, estriol.

00:38:52.060 | How much of each one of them?

00:38:53.780 | Natural or synthetic?

00:38:55.620 | Go try to figure all of that out.

00:38:57.660 | And the second complication is,

00:38:59.780 | it's often hard to say anything about what estrogen does,

00:39:03.500 | outside the context of what progesterone is doing.

00:39:07.020 | And often it's not the absolute levels of either,

00:39:10.040 | it's the ratio of the two.

00:39:11.940 | This is such a more complicated endocrine system

00:39:15.460 | than testosterone.

00:39:17.700 | And because you have to generate dramatic cyclicity

00:39:22.700 | that no male hypothalamus ever has to dream of.

00:39:27.420 | It's a much, much more complicated system.

00:39:30.360 | Thus, it's a lot more complicated to understand

00:39:33.380 | let alone like figure out what the ideal benefits are of it.

00:39:38.380 | - Yeah, I don't know what to make of the literature

00:39:42.820 | on dropping rates of testosterone

00:39:46.060 | and endocrine disruptors.

00:39:48.380 | I was at Berkeley when Tyrone Hayes published his data

00:39:51.060 | on these frogs that were drinking water

00:39:53.720 | from various locations throughout the United States,

00:39:55.860 | not just in California,

00:39:57.220 | and seeing very severe endocrine disruption

00:40:01.060 | through blockade and of androgen receptors

00:40:04.880 | and all sorts of issues.

00:40:05.860 | And you hear this all the time now

00:40:07.500 | that sperm counts are dropping,

00:40:09.140 | that there are all these endocrine disruptors,

00:40:11.100 | that there's birth control in the water,

00:40:13.460 | in the drinking water.

00:40:14.540 | It all starts to sound a little crazy.

00:40:16.680 | And yet I've also been fooled before by,

00:40:21.140 | I guess a good example would be,

00:40:24.500 | there's a lot of crazy stuff in the world online

00:40:26.980 | about all the terrible stuff in highly processed foods.

00:40:29.760 | And yet you've got very respectable people,

00:40:31.980 | endocrinologists at UCSF, like Robert Lustig saying,

00:40:34.860 | yeah, a lot of these hidden sugars and these emulsifiers,

00:40:38.020 | they're causing real problems.

00:40:39.220 | So I've become more open-minded about the question.

00:40:42.920 | And so are we suffering from drops in sperm counts

00:40:48.940 | and testosterone and estrogen and fertility

00:40:51.960 | as a consequence of endocrine disruptors

00:40:54.560 | in the environments and food,

00:40:56.580 | or because of social reasons?

00:40:59.580 | Is there anything that we can hang our hat on,

00:41:01.520 | like real data that you're confident in,

00:41:04.060 | or is it just a mess?

00:41:05.260 | - No, the phenomenon does appear to be quite real.

00:41:09.820 | Cross-sectional studies, human populations,

00:41:14.380 | or I still don't understand why this was one

00:41:16.880 | of the first things that Hayes spotted,

00:41:19.140 | decreasing testicle size in crocodiles.

00:41:22.700 | Go figure why that was one of the first contributions

00:41:26.740 | to this.

00:41:27.700 | And I think the phenomenon is absolutely real.

00:41:30.660 | And what you're then left with is two classic challenges,

00:41:34.780 | which is this is correlated with something broad,

00:41:38.320 | environmental toxins, which ones, how much, when, et cetera.

00:41:43.320 | And the other one always being, well, okay, dropping.

00:41:47.180 | Is it dropping enough to make a difference?

00:41:49.120 | How big of an effect is this?

00:41:50.620 | And those are where the juries are still out.

00:41:54.060 | - Yeah, it's an area that I know there's a lot

00:41:55.940 | of interest in, and you've got groups of people

00:41:58.940 | who won't touch a receipt at a store

00:42:00.740 | because of the BPAs that are on the inks of the,

00:42:03.580 | and then you've got people who don't care about those things.

00:42:07.460 | It is a fascinating area,

00:42:09.340 | and I hope that more biology will be done there soon.

00:42:13.060 | I'd like to briefly return to stress.

00:42:15.680 | You described a study once about two rats,

00:42:22.860 | one running on a wheel voluntarily,

00:42:26.220 | one who's basically stuck in a running wheel

00:42:30.260 | and is forced to run anytime rat number one runs.

00:42:33.340 | So in one case, the rat is voluntarily exercising,

00:42:36.740 | and in the other case,

00:42:37.700 | the rat is being forced to go to PE class, so to speak,

00:42:41.620 | but really, and seeing divergent effects on biology.

00:42:46.620 | And I'd like to just touch into this

00:42:49.060 | and use it as kind of a case study

00:42:50.620 | for stress mitigation in general.

00:42:52.980 | I'm rather obsessed, and our colleague, David Spiegel,

00:42:57.020 | Associate Chair of Psychiatry at Stanford,

00:42:58.660 | is obsessed with this question

00:43:00.400 | of how humans can start to mitigate their own stress.

00:43:03.960 | What do you think about stress mitigation,

00:43:07.780 | and what should we do as individuals and as families

00:43:12.320 | and as a culture to try and encourage people

00:43:14.740 | to mitigate their stress,

00:43:16.620 | but in ways that are not going to turn us

00:43:19.080 | into rat number two, where we're being forced

00:43:21.240 | to mitigate our own stress

00:43:22.520 | and therefore becomes more stressful?

00:43:24.820 | - And what you see is rat number one

00:43:27.420 | gets all the benefits of exercise.

00:43:30.040 | Rat number two gets all the downsides of severe stress

00:43:34.100 | with the same exact muscle expenditure

00:43:37.720 | and movements going on, perfectly yoked,

00:43:40.920 | great example that it's the interpretation in your head.

00:43:45.040 | And I haven't kept up with that literature,

00:43:47.800 | but I'll bet you rat number two

00:43:49.980 | is having a whole lot more activity in its amygdala

00:43:53.220 | than is rat number one.

00:43:54.600 | Okay, so stress mitigation.

00:43:59.020 | Anything I should say here, I should preface with,

00:44:02.460 | reasonably good at telling people what's gonna happen

00:44:06.780 | if they don't manage their stress,

00:44:08.760 | but I'm terrible at actually like managing stress

00:44:12.460 | or advising how to manage it.

00:44:14.620 | I'm much better with the bad news aspect of it,

00:44:18.180 | but what you see is by now just a classic literature,

00:44:23.180 | half a century old, sort of showing

00:44:25.880 | what are the building blocks of stress.

00:44:29.420 | Not, ooh, you step outside

00:44:31.400 | and you've been gored by an elephant

00:44:33.000 | and can you grow from your experience

00:44:36.880 | and what doesn't kill you makes you stronger.

00:44:39.600 | You could have a stress response,

00:44:41.260 | but you're in the realm of the gray zone

00:44:44.940 | of ambiguous social interactions, that sort of thing.

00:44:48.900 | Some people have massive stress responses,

00:44:51.260 | others not at all in between enjoy it.

00:44:53.760 | Like what are the building blocks

00:44:55.460 | of what makes psychological stress stressful?

00:44:58.140 | And the first one is exactly what is brought up

00:45:01.500 | by that running study.

00:45:03.660 | Do you have a sense of control?

00:45:06.480 | A sense of control makes stressors less stressful.

00:45:10.360 | And the running wheel shows that

00:45:12.460 | or studies where you, you lab rat

00:45:15.780 | or you college freshmen volunteer

00:45:18.380 | have been trained that by pressing the lever,

00:45:20.580 | you're less likely to get a shock.

00:45:22.840 | And today you're at the lever there working away

00:45:25.780 | and unbeknownst to you, the lever has been turned off

00:45:28.660 | and it has no effect on shock frequency,

00:45:31.240 | but because you think you have some control,

00:45:33.560 | you have less of a stress response.

00:45:35.440 | If you were a rat and doing this day in and day out,

00:45:38.060 | you're less likely to get an ulcer.

00:45:40.140 | So a sense of control.

00:45:41.980 | Related to that is a sense of predictability.

00:45:46.380 | Rat gets shocked, human gets shocked, whatever.

00:45:49.440 | And the scenario either is the shocks come now and then,

00:45:53.160 | or the shocks come now and then,

00:45:54.700 | and 10 seconds before a little warning light comes on.

00:45:59.080 | And when you get the warning light,

00:46:00.920 | the shocks aren't as stressful.

00:46:03.260 | You got predictability

00:46:05.020 | because if you're not getting warning lights,

00:46:07.460 | any second you could be a half second away

00:46:10.080 | from the next shock, you get a warning light

00:46:13.020 | and you know that if there isn't one,

00:46:14.940 | you've got at least 10 seconds worth of relaxation.

00:46:17.940 | You know what's coming.

00:46:18.980 | You can prepare your coping responses

00:46:22.420 | and best of all, afterward,

00:46:24.260 | you know when you're finally safe,

00:46:26.580 | when you can recover from it.

00:46:28.620 | And that's enormously protective.

00:46:32.020 | Others, outlet for frustration.

00:46:35.340 | You take a rat who's getting shocked

00:46:37.540 | and if it could run on a running wheel,

00:46:39.620 | that's a protective thing.

00:46:41.360 | It's doing it voluntarily.

00:46:43.200 | If you've got a rat and it can gnaw on a bar of wood,

00:46:47.280 | a stressor is less stressful.

00:46:50.120 | Unfortunately, if you have a rat or primate or human

00:46:54.460 | and they're stressed,

00:46:55.620 | the ability to aggressively dump on somebody smaller

00:47:00.020 | and weaker also reduces the stress response

00:47:03.420 | and displacement aggression,

00:47:05.220 | and the fact that displacement aggression reduces stress

00:47:08.760 | accounts for a huge percentage of Earth's unhappiness.

00:47:12.920 | So all of those variables get social support as well.

00:47:16.100 | That's a good one.

00:47:16.940 | Interpreting circumstances,

00:47:18.680 | being good news rather than bad, hooray.

00:47:20.860 | So you've got this very simple sort of take home recipe

00:47:24.700 | of go out and get as much control

00:47:27.300 | and as much predictability and as many outlets

00:47:30.120 | and as much social support as possible,

00:47:32.460 | and you're gonna do just fine.

00:47:33.940 | And you go out and do that

00:47:35.220 | and that's a recipe for total disaster

00:47:37.980 | because it's much, much more subtle than that.

00:47:41.700 | One great example.

00:47:43.420 | Okay, so you're getting shocks.

00:47:44.960 | Do you want a warning beforehand?

00:47:47.120 | Get a little warning light 10 seconds before each shock.

00:47:49.720 | It's wonderfully protective.

00:47:51.620 | Get a warning light one second before the shock.

00:47:56.620 | Doesn't do anything.

00:47:58.060 | There's not enough time for you

00:47:59.180 | to get the psychological benefits of the anticipation.

00:48:03.380 | Now instead, get the little warning coming on two minutes

00:48:07.360 | before each shock and it's gonna make things worse

00:48:10.940 | because you're not gonna be sitting there like,

00:48:13.460 | you know, reveling in sort of your sense of predictability

00:48:18.780 | and it's soon gonna be over.

00:48:20.300 | You're gonna be sitting there for two minutes saying,

00:48:22.660 | damn, here it comes.

00:48:24.360 | Predictive information only works in a narrow domain.

00:48:28.840 | Similarly, control.

00:48:31.820 | Do you wanna have a sense of control in the face of stress?

00:48:35.300 | And the answer is only if it is a mild to moderate stressor

00:48:40.300 | because what's happening then,

00:48:43.180 | your sense of control is completely independent

00:48:45.440 | of the reality of whether you have control or not.

00:48:48.220 | But in the face of mild to moderate stressors,

00:48:50.700 | a sense of control gets interpreted as,

00:48:53.660 | wow, look how much worse things could have been.

00:48:57.580 | Thank God I have control.

00:48:59.300 | I'm on top of this to master my fate.

00:49:00.860 | In contrast, if it's a major stressor,

00:49:04.320 | all that a, you know, arbitrary sense of control does

00:49:08.280 | is make you think, oh my God,

00:49:10.660 | look how much better it could have been.

00:49:13.460 | I could have prevented it.

00:49:15.100 | And we all know that intuitively,

00:49:16.860 | like we do that in the face of people's worst stressors.

00:49:21.380 | Nobody could have stopped the car

00:49:23.380 | the way the kids suddenly jumped out.

00:49:25.980 | It wouldn't have mattered if you had gotten them

00:49:28.300 | to the doctor a month ago instead of now,

00:49:31.260 | it wouldn't have made me,

00:49:32.320 | you didn't actually have any control.

00:49:35.340 | And what you see is you absolutely want to have

00:49:39.200 | a huge sense of control over mild to moderate stressors

00:49:42.940 | and especially ones that result in a good outcome.

00:49:45.460 | Hooray for me.

00:49:46.780 | And in the face of horrible stressors,

00:49:50.180 | what you want to do is like self-deception

00:49:54.820 | and like truth and beauty don't necessarily go hand in hand

00:49:59.120 | at that point.

00:50:00.380 | And that's why stress management techniques

00:50:03.020 | about control and predictability

00:50:05.140 | wind up being far worse than neutral

00:50:07.700 | if you're preaching that to somebody homeless

00:50:10.960 | or somebody with terminal cancer

00:50:13.280 | or somebody who's a refugee,

00:50:15.940 | tell a neurotic middle-class person

00:50:18.500 | that they have the psychological tools

00:50:20.780 | to turn, you know, hell into heaven.

00:50:23.400 | And there's some truth to that.

00:50:24.980 | Do the same thing to somebody

00:50:26.720 | who's going through a real hell.

00:50:29.040 | And that's just privileged, you know, heartlessness

00:50:34.040 | to do that because that doesn't work.

00:50:37.160 | More and more, you know, outlets,

00:50:39.220 | if your outlets are damaging,

00:50:41.040 | that's not a good way to mitigate stress.

00:50:43.100 | Social support.

00:50:44.300 | If you're confusing mere acquaintances

00:50:46.620 | for real social support,

00:50:48.340 | you're going to have the rug pulled out

00:50:49.720 | from under you at some point.

00:50:51.240 | If you're mistaking social support for being,

00:50:54.360 | going and bitching and moaning and demanding supportiveness

00:50:57.400 | from everyone around you,

00:50:59.040 | rather than you doing some of that reciprocally,

00:51:01.980 | that's not going to work very well either.

00:51:04.620 | So, you know, it's not simple.

00:51:07.580 | It's not for nothing that lots of us are really lousy at,

00:51:12.220 | like being good friends and things like that

00:51:15.140 | and why it takes a lot of work to like do it right.

00:51:19.700 | Because, you know, you do it wrong

00:51:22.200 | and it may temporarily seem like a great thing,

00:51:25.220 | but when it turns out to be completely misplaced faith,

00:51:29.340 | you're going to be feeling worse than before you started.

00:51:32.140 | - Interesting.

00:51:33.960 | These days, there's a lot of interest

00:51:35.400 | in using physical practices to mitigate stress.

00:51:38.360 | You know, trying to get out of the ruminating

00:51:40.980 | and to some extent take control of neural circuits

00:51:45.360 | in the brain by using exercise

00:51:48.320 | and using breathing and hypnosis.

00:51:51.340 | And of course, hypnosis has a mental component as well.

00:51:55.280 | What are your thoughts on stress mitigation

00:51:59.380 | from the standpoint of, okay,

00:52:00.780 | so we don't want to be rat number two.

00:52:02.420 | We want to select something for ourselves.

00:52:04.340 | So we have to take the initiative for ourselves.

00:52:07.680 | Being forced into exercising is not,

00:52:10.380 | it could actually have negative health effects perhaps.

00:52:13.240 | So we need to pick something that we like.

00:52:14.980 | We need to take control of it.

00:52:16.600 | In terms of supporting other people,

00:52:19.700 | you touched on that a bit.

00:52:21.300 | What is the best way to support other people?

00:52:23.020 | Is it to talk about the stressful thing?

00:52:25.620 | I mean, I'm not asking you to play psychologist here,

00:52:27.640 | but I find divergent data on this.

00:52:30.660 | You know, we can spin ourselves up into a lather

00:52:34.740 | by ruminating on something.

00:52:36.700 | And language seems to me like it's a wonderful tool,

00:52:41.100 | but it's also a fairly deprived tool

00:52:44.640 | because it doesn't really get into the core

00:52:46.620 | of our physiology like something like breathing would.

00:52:49.900 | So what are your thoughts on more,

00:52:51.800 | for lack of a better way to put it,

00:52:54.220 | more head-centered cognitive approaches to stress mitigation

00:52:57.580 | versus kind of going at the core physiology,

00:53:00.420 | cold showers now, or even a thing to some extent,

00:53:04.060 | you know, just to get people stress acclimated,

00:53:06.340 | voluntarily taking cold showers, you know?

00:53:08.640 | - That makes some sense physiologically preconditioning

00:53:13.820 | for when the real stressors come.

00:53:16.460 | In terms of what you bring up, oh, transcendental meditation,

00:53:20.740 | mindfulness, exercise, prayer,

00:53:24.520 | sort of reflecting on gratitude, all that sort of thing.

00:53:29.340 | Collectively, they work on the average.

00:53:32.720 | They work in terms of they can lower heart rate

00:53:35.280 | and cholesterol levels and have all sorts of good outcomes,

00:53:38.900 | but they come with provisos.

00:53:40.980 | One is exactly the caveat that comes out

00:53:43.820 | of the running wheel study is it doesn't matter

00:53:46.620 | how many of your friends swear

00:53:48.180 | by this stress management technique.

00:53:50.420 | If doing it makes you want to scream your head off

00:53:53.120 | after 10 seconds,

00:53:54.820 | that's not the one that's going to work for you.

00:53:56.580 | So, you know, read the fine print and the testimonials,

00:54:00.420 | but it's gotta be something that works for you.

00:54:02.220 | Another one is the stress management type techniques

00:54:06.700 | that work, you can't save them for the weekend.

00:54:11.140 | You can't save them for when you're stuck on hold

00:54:13.500 | on the phone with Muzak for two minutes.

00:54:16.060 | It's gotta be something where you stop what you're doing

00:54:20.380 | and do it virtually daily or every other day

00:54:23.420 | and spend 20, 30 minutes doing it.

00:54:26.260 | And what you see coming out of that

00:54:28.220 | is this like 80/20 rule from economics.

00:54:32.540 | 80/20, 80% of the complaints in the store

00:54:35.340 | come from 20% of the customers, things like that.

00:54:37.860 | What you see is if your entire life consists

00:54:40.980 | of every single thing on your shoulders

00:54:45.260 | that you can't say no to 24/7,

00:54:48.700 | if you've stopped that and finally said,

00:54:52.180 | my wellbeing is important enough,

00:54:54.340 | that I'm finally going to say no to some of the stuff

00:54:56.420 | that I can't say no to,

00:54:57.780 | and I'm going to do it every day for 20 minutes,

00:55:00.540 | whatever stress management technique you then do

00:55:03.060 | in those 20 minutes, short of who knows what,

00:55:06.240 | you're already 80% of the way there

00:55:08.700 | simply by having decided your wellbeing is important enough

00:55:13.340 | that you're going to stop every single day

00:55:15.860 | and have that as priority.

00:55:17.700 | And that's exactly the same finding

00:55:19.300 | that you find people with chronic depression untreated

00:55:23.020 | that merely calling and getting an appointment

00:55:26.040 | to see a mental health professional,

00:55:28.200 | people start feeling better already

00:55:30.640 | because it's evidence that you've been activated

00:55:34.460 | and you matter enough to do this

00:55:37.140 | and you could conceive that this would actually

00:55:39.140 | have a good outcome rather than a hopeless one.

00:55:41.940 | Just doing something meditative

00:55:44.940 | or reflective every day or so,

00:55:47.780 | and it hardly even matters which one you're doing.

00:55:52.020 | And what comes out of that is thus another warning,

00:55:55.100 | which is do not trust anybody

00:55:57.940 | who says it has been scientifically proven

00:56:00.740 | that their brand of stress management

00:56:03.260 | works better than the other ones.

00:56:04.940 | Just watch your wallet at that point.

00:56:08.100 | - Yeah, amen.

00:56:09.040 | I think one of the core goals of my lab

00:56:12.100 | and David Spiegel's lab,

00:56:13.420 | and I know you've worked with David

00:56:14.620 | and published papers with David as well,

00:56:16.520 | is to really try and find out

00:56:18.340 | what are the various entry points

00:56:20.300 | to this thing that we call the autonomic nervous system

00:56:22.900 | and the stress system and the systems that,

00:56:25.100 | when gone unchecked, really can take us down a dark path.

00:56:28.900 | And the idea that there are so many entry points

00:56:31.980 | is really the one that keeps,

00:56:33.500 | what the data keep telling us over and over again.

00:56:35.460 | So there's no magic breathing tool or exercise.

00:56:39.060 | It's any variety of those or one of those.

00:56:42.700 | And again, we come back to this idea

00:56:44.580 | that it's the one that you select

00:56:45.860 | and the one that you make space for,

00:56:47.580 | and it's the one that you hopefully enjoy

00:56:50.680 | that's going to work best in terms of physiology.

00:56:54.200 | - I'm one that's benign

00:56:56.060 | for those people who were stuck around you.

00:56:58.420 | - Right, right, absolutely.

00:57:00.500 | And that brings me to this question of,

00:57:03.100 | I find it amazing that how we perceive an event

00:57:08.100 | and whether or not we chose to be in that event or not

00:57:12.220 | can have such incredibly different effects

00:57:16.140 | on circuitry of the brain and circuitry of the body

00:57:19.500 | and biology of cells.

00:57:21.100 | And in some ways it boggles my mind,

00:57:24.060 | like how can a decision made presumably

00:57:26.700 | with the prefrontal cortex,

00:57:28.380 | although other parts of the brain as well,

00:57:30.260 | how can that change essentially the polarity

00:57:33.420 | of a response in the body?

00:57:36.260 | And I mean, you've talked before about type A personalities

00:57:39.660 | and we don't have to go into all the detail there

00:57:41.780 | for sake of time,

00:57:42.620 | but it is interesting that the effects of endothelial cells,

00:57:46.260 | I mean, literally of the size of the portals for blood

00:57:51.260 | are in opposite direction,

00:57:53.300 | depending on whether or not somebody

00:57:55.140 | wants to be in a situation, is a highly motivated person.

00:57:58.500 | Maybe you could just give us the top contour of that,

00:58:01.100 | because I think it really illustrates this principle

00:58:03.900 | so beautifully.

00:58:04.860 | And then maybe if you would,

00:58:06.660 | you could just speculate on how the brain might have

00:58:10.320 | this switch to turn one experience from terrible

00:58:14.740 | to beneficial or from beneficial to terrible.

00:58:18.660 | It's really fascinating.

00:58:20.100 | - Well, I mean, all you need to do is like tonight

00:58:24.180 | before you're going to sleep and you're lying in bed

00:58:27.780 | and you're nice and drowsy

00:58:29.180 | and your heart's beating nice and slow,

00:58:31.700 | you'll start thinking about the fact that, you know,

00:58:34.420 | that heart isn't going to beat forever.

00:58:36.820 | And imagine your toes getting cold

00:58:40.580 | after we're going to imagine the flow of blood

00:58:43.140 | coming to a halt and all of you clotting.

00:58:46.180 | And if you're really,

00:58:47.340 | you're going to be doing something with your physiology

00:58:49.700 | at that point that 99% of mammals out there only do

00:58:52.820 | if they're running frantically.

00:58:54.820 | And you're going to be turning on

00:58:56.180 | your synthetic stress response with thought,

00:58:58.420 | with emotions, with memory.

00:59:00.420 | And the measure of that is just how much the cortex

00:59:05.420 | and the limbic system sends projections down

00:59:09.060 | to all the autonomic regulators in the brain.

00:59:12.540 | You can think autonomic regulatory neurons into action

00:59:17.340 | in ways that only other animals can do

00:59:19.500 | with like extremes of environmental circumstances.

00:59:24.500 | Given that and the autonomic rule,

00:59:27.940 | I mean, the other big challenge in understanding it

00:59:30.420 | is gigantic individual differences.

00:59:34.140 | And that's, you know,

00:59:37.700 | we talk about the optimal amount of stress

00:59:40.820 | that counts as stimulation.

00:59:42.340 | And in general, that's stress that's not too severe

00:59:46.660 | and doesn't go on for too long

00:59:48.060 | and is overall in a benevolent setting.

00:59:50.180 | And under those conditions,

00:59:51.540 | we love being stressed by something unexpected

00:59:54.780 | and out of control and predictability,

00:59:56.540 | like a really interesting plot turn

00:59:58.820 | in the movie you're watching.

01:00:00.300 | That's great, but you get the individual differences

01:00:03.700 | that somehow has to accommodate the fact that

01:00:06.380 | for some people, the perfect stimulatory amount of stress

01:00:10.780 | is like getting up early for an Audubon bird watching walk

01:00:15.500 | next Sunday morning.

01:00:16.740 | And for somebody else,

01:00:17.740 | it's signing up to be like a mercenary in Yemen.

01:00:21.220 | And tremendous individual differences

01:00:24.700 | that swamp any simple, you know, prescriptions.

01:00:29.700 | - Yeah, the prefrontal cortex,

01:00:33.260 | this thinking machinery that we all harbor,

01:00:35.460 | it's such a double-edged sword.

01:00:37.900 | And what's remarkable to me is how the areas of the brain,

01:00:42.900 | like the hypothalamus and the amygdala,

01:00:44.860 | they're sort of like switches.

01:00:46.460 | I mean, there's context and there's gain control.

01:00:49.100 | You talked about the gain control by testosterone, et cetera,

01:00:52.520 | but they're really like switches.

01:00:53.780 | I mean, if you stimulate ventromedial hypothalamus,

01:00:56.580 | you get the right neurons,

01:00:57.500 | an animal will try and kill even an object

01:01:00.020 | that's sitting next to it.

01:01:00.840 | You tickle some other neurons,

01:01:02.180 | it'll try and mate with that same object.

01:01:04.220 | I mean, it's really wild.

01:01:05.920 | I think there are probably rules to prefrontal cortex also,

01:01:09.460 | but it sounds like the context, plural,

01:01:13.520 | from which prefrontal cortex can draw from

01:01:16.820 | is probably infinite.

01:01:18.780 | So that we could probably learn to perceive threat

01:01:21.920 | in anything, whether or not it's another group

01:01:23.900 | or whether or not it's science or whether or not

01:01:26.580 | it's somebody's version of the shape of the earth

01:01:29.540 | versus another.

01:01:30.380 | I mean, it's like you can plug in anything to this system

01:01:33.820 | and give it enough data.

01:01:35.300 | And I think it sounds like you could drive a fear response

01:01:37.860 | or a love response.

01:01:39.100 | Is that overstepping?

01:01:40.580 | - Or a mixed, hardly ambivalent one

01:01:44.500 | that is changing by the millisecond

01:01:46.900 | and then like initially contradictory?

01:01:49.940 | No, that's absolutely the case.

01:01:51.500 | And the prefrontal cortex,

01:01:53.420 | I more than once have regretted having like wasted 30 years

01:01:58.420 | of my life studying the hippocampus

01:02:01.060 | when I should have been studying the prefrontal cortex

01:02:03.660 | because it's so much more interesting what it does.

01:02:06.460 | And it's all this contextual stuff.

01:02:09.460 | It's all the ways in which it's not okay to lie

01:02:13.180 | in this setting, but it's a great thing in another.

01:02:16.420 | It's not okay to kill unless you do it to them.

01:02:19.660 | And then you get a medal.

01:02:20.620 | It's not all of this social context and moral relativity

01:02:25.620 | and situational ethics stuff.

01:02:29.100 | That's the prefrontal cortex that's got to master that.

01:02:32.020 | And that winds up meaning that's the place in your brain

01:02:36.980 | more than anywhere where you say your perception of things

01:02:41.980 | can powerfully influence the reality

01:02:44.460 | of what's coming into you.

01:02:46.420 | I mean, great example, just harking back to testosterone.

01:02:51.420 | Okay, so exercise boosts up testosterone levels.

01:02:54.900 | Does exercise and success do it more than exercise

01:02:58.660 | and failure of literature back in the '80s or so,

01:03:02.580 | looking at outcomes of marathons.

01:03:05.060 | Did testosterone rise more in the people who win

01:03:07.780 | than the losers?

01:03:09.140 | Wrestling matches, things of that sort

01:03:11.460 | with a simple prediction and the answer wound up being

01:03:14.220 | you didn't see a simple answer.

01:03:16.620 | Okay, you win the marathon.

01:03:18.660 | That's not necessarily an increase,

01:03:20.980 | a predictor of increased testosterone.

01:03:23.140 | What's that about?

01:03:24.460 | And then you find like the winner, testosterone decreases.

01:03:29.460 | And you find out the guy who came in 73rd

01:03:32.900 | is having a massive testosterone increase.

01:03:35.860 | Whoa, what's that about?

01:03:37.820 | What's that about is far more human subtlety.

01:03:40.500 | The guy who won the race has a decline in testosterone

01:03:44.020 | because he came in three minutes later

01:03:46.020 | than he really, really was expecting.

01:03:48.460 | And everybody now is going to be writing it up

01:03:50.740 | about how he's over the hill.

01:03:52.700 | And the guy who came in 73rd

01:03:54.500 | is having a boost of testosterone

01:03:56.420 | because he was assuming he'd be dead from a heart attack

01:03:59.260 | by the third mile and instead he managed to finish.

01:04:02.500 | It's this interpretive stuff going on in there

01:04:05.380 | and that's what prefrontal cortex is about.

01:04:08.300 | - Amazing.

01:04:09.220 | It raises this question of cognitive flexibility.

01:04:13.700 | Can we tell ourselves that something is good for us

01:04:18.700 | even if we're not enjoying it?

01:04:21.020 | Can we wriggle around these corners

01:04:23.260 | of choosing the exercise or doing the...

01:04:28.260 | I personally am not a big fan of long bouts of meditation

01:04:34.400 | but I've benefited tremendously

01:04:35.620 | from things like dedicated breathing

01:04:37.860 | and shorter rounds of meditation.

01:04:40.220 | Can I tell myself that it's good for me

01:04:42.740 | and wriggle around the corner

01:04:44.300 | and get my physiology working the way I want?

01:04:46.660 | Do we have cognitive flexibility?

01:04:48.540 | Can I be that third place runner and tell myself,

01:04:52.000 | well, at least I came in, I wanted to win so badly.

01:04:56.560 | That was my primary goal.

01:04:57.960 | But another goal was to beat my previous time

01:05:01.260 | and I did do that.

01:05:02.380 | And so, I mean, to what extent can we toggle

01:05:07.380 | this relationship between the prefrontal cortex

01:05:11.100 | and these other more primitive systems?

01:05:14.720 | - Oh, an enormous amount.

01:05:16.800 | For example, being low in a hierarchy

01:05:23.260 | is generally bad for health

01:05:25.100 | and like every mammal out there, including us.

01:05:27.940 | But we do something special,

01:05:29.340 | which is we can be part of multiple hierarchies

01:05:32.040 | at the same time.

01:05:33.460 | And while you may be low ranking in one of them,

01:05:36.320 | you could be extremely high ranking in another.

01:05:38.860 | You're like have the crappiest job in your corporation,

01:05:42.940 | but you're the captain of the team softball,

01:05:45.340 | of the softball team this year for the company.

01:05:48.060 | And you better bet that's somebody

01:05:49.860 | who's gonna find all sorts of ways

01:05:51.820 | to decide that nine to five Monday to Friday

01:05:54.300 | is just stupid paying the bills.

01:05:56.540 | And what really matters is the prestige on the weekend.

01:06:00.500 | You're poor, but you're the deacon of your church here.

01:06:04.500 | And so we can play all sorts of psychological games

01:06:07.140 | with that.

01:06:07.980 | One of the most like consistent, reliable ones

01:06:11.620 | that we do and need to use the frontal cortex like crazy

01:06:14.980 | is somebody does something rotten

01:06:18.500 | and you need to attribute it.

01:06:20.360 | And the answer is they did something rotten

01:06:22.700 | because they're rotten.

01:06:23.980 | Always have been, always will be

01:06:25.800 | this constitutional explanation.

01:06:28.220 | You do something rotten to somebody

01:06:30.340 | and how do you explain it afterward?

01:06:32.340 | A situational one.

01:06:34.060 | I was tired, I was stressed in this sort of setting.

01:06:38.100 | I misunderstood this.

01:06:40.260 | We're best at excusing ourselves from bad things

01:06:43.900 | because we have access to our inner lives

01:06:46.500 | and we've got prefrontal cortexes that are great

01:06:49.260 | at coming up with a situational explanation

01:06:52.340 | rather than, hey, maybe you're just

01:06:54.540 | like a selfish rotten human and you need to change.

01:06:57.860 | And that's all prefrontal cortex.

01:07:00.020 | And we do that every time we don't let somebody,

01:07:04.620 | you know, merge in the lane in front of us

01:07:07.040 | even though you curse somebody who does the same thing

01:07:09.780 | to you and, you know, endlessly.

01:07:13.760 | - I love it.

01:07:16.140 | Your statement about the fact

01:07:18.060 | that we can select multiple hierarchies to participate in

01:07:21.140 | to me seems like a particularly important one nowadays

01:07:25.880 | with social media being so prevalent.

01:07:28.940 | I know you're not particularly active on social media

01:07:31.340 | although you might be pleasantly, or I don't know,

01:07:34.100 | unpleasantly surprised to find out

01:07:35.380 | that there's a lot of positive discussion

01:07:37.560 | about you and your work.

01:07:38.880 | So you don't even need to be on there.

01:07:40.220 | We'll just continue to discuss your work.

01:07:42.540 | But what's interesting about social media I've found

01:07:46.420 | is that the context is very, very broad.

01:07:49.140 | I mean, one could argue that who one selects to follow

01:07:52.140 | and which news articles you're reading, et cetera,

01:07:54.000 | can create a kind of a funneling of information

01:07:56.200 | that itself can be dangerous.

01:07:57.860 | You know, more verification of crazy ideas

01:08:01.220 | or even just less exposure to new ideas.

01:08:04.280 | But there's also this idea

01:08:07.100 | that social media is an incredibly broad context.

01:08:11.060 | So as you scroll through a feed,

01:08:13.020 | it's no longer like being in your eighth grade classroom

01:08:15.760 | or your office or your faculty meeting.

01:08:18.580 | You are being exposed to thousands,

01:08:21.440 | if not millions of contexts.

01:08:23.900 | This meal, that soccer game, this person's body,

01:08:27.200 | this person's intellect.

01:08:29.180 | YouTube is another example.

01:08:30.700 | It's a vast, vast landscape.

01:08:34.060 | So the context is completely mishmash.

01:08:37.600 | Whereas I'm assuming we evolved, I think we did evolve,

01:08:41.020 | under contexts that were much more constrained.

01:08:43.460 | We interacted with a limited number of individuals

01:08:45.580 | and a limited number of different domains.

01:08:47.780 | Seasons tend to constrain us all.

01:08:50.380 | And of course, then we got phones and televisions

01:08:53.060 | and this started to expand.

01:08:54.140 | But now more than ever, our brain,

01:08:56.820 | our prefrontal cortex and our sense of where we exist

01:09:00.160 | in these multiple hierarchies

01:09:02.580 | has essentially wicked out into infinity.

01:09:06.620 | How do you think this might be interacting

01:09:08.700 | with some of these more primitive systems

01:09:12.260 | and other aspects of our biology?

01:09:15.960 | - Well, I think what you get is in some ways,

01:09:19.620 | the punchline of what's most human about humans,

01:09:24.540 | which is over and over, we use the exact same blueprint,

01:09:28.620 | the same hormones, the same kinases, the same receptors,

01:09:33.100 | the same everything.

01:09:34.440 | We're built out of the exact same stuff

01:09:36.940 | as all these other species out there.

01:09:39.020 | And then we go and use it in a completely novel way.

01:09:42.740 | And usually in terms of being able to abstract stuff

01:09:47.740 | over space and time in dramatic ways.

01:09:51.780 | So, okay, you're a low ranking baboon

01:09:55.020 | and you can feel badly because you just like killed a rabbit

01:09:58.820 | and you're about to eat and some higher ranking guy

01:10:01.140 | boots you off and takes it away from you

01:10:03.500 | and you feel crummy and it's stressful and you're unhappy.

01:10:07.740 | We are doing the exact same things with like our brain

01:10:12.460 | and bodies when we're losing a sense of self-esteem,

01:10:15.940 | but we can do it by watching a movie character on the screen

01:10:19.920 | and feeling inadequate compared to like how wonderful

01:10:23.540 | or attractive they are.

01:10:25.060 | We can do it by somebody driving past us in an expensive car

01:10:29.460 | and we don't even see their face and you can feel belittled

01:10:33.440 | by your own socioeconomic status.

01:10:35.920 | You can watch like the lifestyles of the rich and famous

01:10:41.000 | or read about what Bezos is up to.

01:10:43.700 | And for some reason decide your life is less fulfilling

01:10:47.560 | because you didn't fly into space for 11 minutes.

01:10:50.700 | And so you can feel miserable about yourself in ways

01:10:54.860 | that no other organism can simply because we can have

01:10:59.860 | our meaningful social networks include like the party

01:11:04.420 | you're reading about on Facebook that you weren't invited to

01:11:07.660 | because it's taking place in Singapore

01:11:09.460 | and you don't know any of those people.

01:11:10.860 | But nonetheless, somehow that could be a means

01:11:13.940 | for you to feel less content with who you've turned out to be

01:11:18.440 | - Do you take steps in your own life

01:11:20.520 | to actively restrict the context in which you think and live

01:11:25.520 | and contemplate in order to enhance your creative life,

01:11:30.880 | your intellectual life, are those steps

01:11:37.220 | that you actively take?

01:11:38.600 | - Well, I very actively don't know how to make use

01:11:43.640 | of anything with social media.

01:11:46.020 | So I guess that counts as my having thus actively chosen

01:11:49.980 | not to learn how.

01:11:51.280 | So that's the case, certainly for the last year and a half,

01:11:55.780 | like lots of people, I've gone through stretches

01:11:58.620 | where I've managed to sort of enforce a moratorium

01:12:01.820 | on looking at the news and that was wonderfully freeing.

01:12:05.440 | I think in the larger sense though,

01:12:08.440 | in addition to me being a neurobiologist,

01:12:12.640 | I've sort of spent decades spending part of each year

01:12:15.440 | studying wild baboons out in a national park in East Africa.

01:12:19.980 | And I'd spend three months a year without electricity,

01:12:24.260 | without phone calls, with going 12 hours a day

01:12:28.440 | without saying a word to somebody.

01:12:30.560 | And when I finally would, it would be somebody,

01:12:33.400 | a nomadic pastoralist guy in a different language.

01:12:37.280 | Yeah, I did 90% of my like insightful thinking

01:12:42.100 | about anything in the laboratory

01:12:44.200 | during those three months each year

01:12:46.000 | and not one in the lab and not one inundated with stuff.

01:12:50.100 | - Well, I think there's sort of a shifting trend

01:12:53.120 | towards trying to create a narrowing of context

01:12:55.940 | that people, and I like what I see.

01:12:59.200 | I have a niece, she's 14 years old

01:13:00.920 | and she and her friends are very good

01:13:02.500 | at putting their phones away.

01:13:04.160 | They say, we're not going to have our phones

01:13:06.180 | for this interaction, especially after,

01:13:09.160 | and I realize we're still somewhat in this,

01:13:11.720 | it's unclear where it's headed,

01:13:13.260 | but 2020 was so restrictive

01:13:15.540 | and she was so separated from her friends.

01:13:17.460 | Now it's let's really focus on being together

01:13:20.540 | and not bring in all these other elements from our phones.

01:13:23.360 | And that brings me great hope for that generation.

01:13:27.380 | Maybe they will, or who knows,

01:13:29.980 | maybe they'll run off and study baboons.

01:13:31.580 | We need more field researchers.

01:13:33.800 | So along the lines of choice,

01:13:36.840 | I'd like to shift gears slightly and talk about free will,

01:13:41.020 | about our ability to make choices at all.

01:13:43.720 | - Well, my personal way out

01:13:48.860 | and left field inflammatory stance is,

01:13:53.040 | I don't think we have a shred of free will.

01:13:55.480 | Despite, you know, 95% of philosophers

01:14:01.760 | and I think probably the majority of neuroscientists

01:14:05.740 | saying that we have free will

01:14:07.580 | in at least some circumstances,

01:14:09.420 | I don't think there's any at all.

01:14:11.860 | And the reason for this is you do something,

01:14:16.860 | you behave, you make a choice, whatever.

01:14:20.480 | And to understand why you did that,

01:14:23.500 | where did that intention come from?

01:14:25.900 | Part of it was due to like the sensory environment

01:14:30.420 | you were in in the previous minute.

01:14:32.560 | Some of it is from the hormone levels

01:14:34.380 | in your bloodstream that morning.

01:14:36.420 | Some of it is from whether you had a wonderful

01:14:40.340 | or stressful last three months

01:14:42.000 | and what sort of neuroplasticity happened.

01:14:44.460 | Part of it is what hormone levels

01:14:46.580 | you were exposed to as a fetus.

01:14:48.980 | Part of it is what culture your ancestors came up with

01:14:52.700 | and thus how you were parented when you were a kid.

01:14:56.220 | All of those are in there

01:14:57.920 | and you can't understand where behavior is coming from

01:15:00.660 | without incorporating all of those.

01:15:03.380 | And at that point, not only are there

01:15:07.940 | all of these relevant factors,

01:15:11.860 | but they're ultimately all one factor.

01:15:15.120 | If you're talking about what evolution

01:15:17.300 | has to do with your behavior,

01:15:19.060 | by definition, you're also talking about genetics.

01:15:22.200 | If you're talking about what your genes

01:15:23.960 | have to do with behavior, by definition,

01:15:26.360 | you're talking about how your brain was constructed

01:15:29.100 | or what proteins are coded for.

01:15:31.280 | If you're talking about like your mood disorder now,

01:15:35.800 | you're talking about the sense of efficacy

01:15:37.960 | you were getting as a five-year-old.

01:15:39.760 | They're all intertwined.

01:15:41.040 | And when you look at all those influences,

01:15:45.220 | basically like the challenge is show me a neuron

01:15:50.220 | that just caused that behavior

01:15:52.380 | or show me a network of neurons

01:15:54.140 | that just caused that behavior

01:15:55.860 | and show me that nothing about what they just did

01:15:59.940 | was influenced by anything from the sensory environment

01:16:04.060 | one second ago to the evolution of your species.

01:16:07.160 | And there's no space in there to fit in

01:16:11.140 | a free will concept that winds up being in your brain,

01:16:16.140 | but not of your brain.

01:16:18.440 | There's simply no wiggle room for it there.

01:16:21.960 | - So I can appreciate that our behaviors and our choices

01:16:26.240 | are the consequence of a long line of dominoes

01:16:29.100 | that fell prior to that behavior.

01:16:32.340 | But is it possible that I can intervene

01:16:36.260 | in the domino effect, so to speak?

01:16:40.120 | In other words, can my recognition of the fact

01:16:44.520 | that genes have heritability, there's an epigenome,

01:16:48.260 | that there's a hormonal context,

01:16:50.780 | there's a historical context,

01:16:52.960 | can the knowledge of that give me some small, small shards

01:16:59.260 | of free will, meaning does it allow me to say,

01:17:02.380 | ah, okay, I accept that my choices are somewhat

01:17:06.020 | predetermined and yet knowing that gives me

01:17:10.000 | some additional layer of control.

01:17:12.920 | Is there any philosophical or biological universe

01:17:17.380 | in which that works?

01:17:19.640 | - Nah.

01:17:21.400 | All of that can produce the wonderfully positive

01:17:28.860 | belief that change can happen.

01:17:30.920 | Even dramatic change, even in the worst of circumstances,

01:17:34.600 | most unlikely people, and change can happen.

01:17:37.620 | Things can change.

01:17:39.800 | Don't be fatalistic, don't decide because we're mechanistic

01:17:43.820 | biological machines that nothing can ever, change can happen.

01:17:48.380 | But where people go off the rails is translating that into

01:17:56.180 | we can change ourselves, we don't, we can't,

01:18:00.900 | 'cause there's no free will.

01:18:02.460 | However, we can be changed by circumstance.

01:18:07.060 | And the point of it is, like, you look at an aplegia,

01:18:12.060 | a sea slug that has learned to retract its gill

01:18:18.020 | in response to a shock on its tail.

01:18:20.780 | You can do like conditioning, Pavlovian conditioning on it,

01:18:24.660 | and it has learned its behavior has been changed

01:18:27.940 | by its environment.

01:18:30.100 | And you hear news about something like horrifically

01:18:34.060 | depressing going on and, you know, refugees and wherever.

01:18:39.060 | And as a result, you feel a little bit more helpless

01:18:45.820 | and a less of a sense of efficacy in the world.

01:18:48.900 | And both of your behaviors have been changed.

01:18:53.240 | - Okay, okay, yeah, I guess that,

01:18:55.160 | but the remarkable thing is it's the exact same neurobiology.

01:19:00.160 | The signal transduction pathways that were happening

01:19:04.380 | in that sea snail incorporate the exact same kinases

01:19:09.380 | and proteases and phosphatases that we do

01:19:13.300 | when you're having mammalian fear conditioning

01:19:16.180 | or when you're learning it's conserved,

01:19:20.060 | it's the exact same thing.

01:19:21.920 | It's simply playing out in obviously

01:19:23.720 | a much, much fancier domain.

01:19:26.140 | And because you have learned that change is possible

01:19:31.140 | despite understanding mechanistically

01:19:36.280 | that we can't change ourselves volitionally,

01:19:39.660 | but because you understand change is possible,

01:19:42.340 | you have just changed the ability of your brain

01:19:45.980 | to respond to optimistic stimuli.

01:19:49.580 | And you have changed the ability of your brain

01:19:52.120 | to now send you in the direction of being exposed

01:19:55.300 | to more information that will seem cheerful

01:19:57.560 | rather than depressing.

01:19:59.120 | Oh my God, that's amazing what Nelson Mandela

01:20:02.900 | and Martin Luther King and all these folks did.

01:20:05.900 | Wow, under the most adverse of circumstances

01:20:08.460 | they were able to do.

01:20:09.800 | Maybe I can also, maybe I can go read more

01:20:13.920 | about people like them to get even more data points

01:20:17.420 | of change to neurochemistry

01:20:20.580 | so that your responses are different now.

01:20:23.500 | And you're tilted a little bit more in that direction

01:20:27.660 | of feeling like you can make a difference

01:20:29.620 | instead of it's all damn hopeless.

01:20:32.320 | So enormous change can happen,

01:20:34.440 | but the last thing that could come out of a view

01:20:37.040 | of we are nothing more or less than the sum of our biology

01:20:41.620 | and its interactions with environment

01:20:43.620 | is to throw up your hands and say,

01:20:45.380 | and thus it's no use trying to change anything.

01:20:48.580 | - So we can acknowledge that change is extremely hard

01:20:53.220 | to impossible, that circumstances can change,

01:20:56.340 | and yet that striving to be better human beings

01:20:59.800 | is still a worthwhile endeavor.

01:21:01.560 | Do I have that correct?

01:21:02.860 | - Absolutely, because simply the knowledge

01:21:06.940 | either from experience or making it to the end

01:21:09.860 | of the right neurobiology class has taught you

01:21:14.000 | that change can happen within a framework

01:21:16.940 | of a mechanistic neurobiology.

01:21:19.680 | You are now more open to being made optimistic

01:21:23.840 | by the good news in the world around you.

01:21:26.060 | You are more likely to be inspired by this or that.

01:21:28.680 | You are more resistant to getting discouraged by bad news

01:21:32.500 | simply 'cause you now understand it's possible.

01:21:36.060 | - Yeah, somebody who spent much of his career

01:21:39.680 | working on the hippocampus, I have to assume

01:21:41.500 | that you are a believer in neuroplasticity,

01:21:43.940 | that neural circuits can change in response to experience,

01:21:46.780 | and that some of the same so-called top-down mechanisms

01:21:49.780 | of prefrontal cortex that we were talking about before

01:21:52.940 | can play a role there, that the decision to try and change

01:21:56.000 | and the pursuit of knowledge and the pursuit of experience

01:21:59.500 | can shape our circuitry and therefore

01:22:01.920 | make us different machines, so to speak.

01:22:05.060 | - Yeah, and not only can, say, prenatal hormone exposure

01:22:10.800 | change the way your brain is being constructed,

01:22:14.100 | but learning that prenatal hormone exposure

01:22:17.280 | can change the construction of your brain

01:22:19.520 | will change your brain right now

01:22:21.940 | and how you think about where your intentions came from.

01:22:26.160 | Wow, maybe that had something to do with it.

01:22:29.080 | The knowledge of the knowledge

01:22:31.600 | is an effector in and of itself.

01:22:34.440 | - That's such an important and powerful statement to hear.

01:22:38.860 | I think that many people think that if a tool,

01:22:42.580 | it doesn't involve a pill or a protocol, that it's useless.

01:22:47.580 | And certainly there are pills and protocols

01:22:51.580 | that are very useful in a variety of contexts

01:22:53.660 | for a variety of things, but the idea that knowledge itself,

01:22:57.900 | or as you put it, knowledge of knowledge, is itself a tool,

01:23:01.620 | I think is a very important concept

01:23:04.100 | for people to embed in their minds.

01:23:07.060 | And listen, I'm so grateful for this discussion

01:23:11.040 | and for you raising these topics.

01:23:13.120 | I think that people, many people know your work

01:23:17.140 | on testosterone, on stress,

01:23:18.720 | and we've covered some of that today.

01:23:19.900 | The work on free will and this idea that we are hopeless

01:23:23.780 | or that we are in total control,

01:23:27.060 | I think I'm realizing in listening to you

01:23:30.220 | that neither is true and that the solution resides

01:23:35.260 | in understanding more about free will and lack of it

01:23:39.700 | and also neuroplasticity.

01:23:42.980 | You're working on a book about free will.

01:23:47.260 | Are you willing to tell us a little bit about that book

01:23:49.820 | and where you are in that process

01:23:51.280 | and what we can look forward to?

01:23:52.900 | - Yeah, it's going really slow.

01:23:56.080 | Title is "Determined, A Science of Life Without Free Will."

01:24:03.260 | And essentially the first half of the book

01:24:05.640 | is trying to convince a reader,

01:24:08.920 | okay, if not that there's no free will whatsoever,

01:24:11.760 | but at least there's a lot less than is normally assumed.

01:24:15.360 | And I'm going through all the standard arguments

01:24:18.660 | for free will and why that doesn't make sense

01:24:22.140 | with 21st century science.

01:24:24.940 | And that has led to reading a lot

01:24:28.260 | of very frustrating philosophers

01:24:31.320 | who basically are willing to admit

01:24:35.020 | that stuff is made out of like atoms and molecules

01:24:39.040 | and like there's a physical reality to the world.

01:24:42.100 | They're not just relying on magic,

01:24:44.200 | but that they believe in free will for magical reasons

01:24:48.180 | and where it doesn't make sense.

01:24:50.100 | Okay, so the first half of the book

01:24:51.780 | is to hopefully convince people

01:24:54.220 | that there's much less free will than they used to think.

01:24:56.980 | And then the second half is this gigantic juncture

01:24:59.900 | built around the fact that I haven't thought

01:25:01.920 | there's any free will since I was like an adolescent.

01:25:06.020 | And despite thinking that way,

01:25:08.240 | I still have absolutely no idea

01:25:10.460 | how you're supposed to function with that belief.

01:25:14.480 | How are you supposed to like go about everyday life

01:25:18.100 | if anything you feel entitled to isn't true,

01:25:23.160 | if any angers and hatreds you feel aren't justified,

01:25:26.620 | if there's no such thing as appropriate,

01:25:29.480 | blame or punishment or praise or reward,

01:25:31.940 | and none of it makes any sense.

01:25:33.840 | And somebody like even compliments you on your haircut

01:25:37.180 | and you've been conditioned to like say,

01:25:39.480 | "Oh, well, thanks as if you had something to do."

01:25:43.140 | How are we supposed to function with that?

01:25:45.180 | And so the second half is wrestling with that.

01:25:51.620 | And what the punchline there is,

01:25:55.940 | is it's gonna be incredibly hard.

01:25:59.060 | And if you think it's gonna be hard

01:26:00.820 | to subtract a notion of free will

01:26:03.660 | out of making sense of like serial murderers,

01:26:07.460 | it's gonna be a thousand times harder

01:26:09.380 | of making sense of when somebody says good job to you.

01:26:14.220 | And 'cause it's the exact same unreality

01:26:18.980 | of sort of our interpretations,

01:26:21.380 | it's gonna be incredibly hard.

01:26:23.640 | But nonetheless, when you look at the history

01:26:27.480 | of how we have subtracted the notion of agency

01:26:32.480 | out of all sorts of realms of blame,

01:26:35.700 | starting with thinking that witches

01:26:38.320 | caused hailstorms 500 years ago,

01:26:41.460 | to the notion that psychodynamically screwed up mothers

01:26:45.460 | caused schizophrenia, we've done it.

01:26:49.400 | We've done it endless number of times.

01:26:51.600 | We've been able to subtract out a sense of volition

01:26:54.720 | in understanding how the world works around us.

01:26:57.720 | And we don't have murderers running amok on the street

01:27:00.940 | and society hasn't collapsed into a puddle.

01:27:04.420 | And in fact, it's a more humane society.

01:27:07.160 | So the good news is it's possible

01:27:11.480 | because we've done it repeatedly in the past,

01:27:14.660 | but it's gonna be hard as hell.

01:27:16.720 | And it's hard as hell to try to write

01:27:18.900 | about that coherently, I'm discovering.

01:27:21.100 | So it's going slowly.

01:27:23.740 | - Well, I speak for many, many people

01:27:26.460 | when I say that we're really excited

01:27:29.740 | for the book when it's done and we will patiently wait.

01:27:33.860 | But with great excitement for the book "Determined,"

01:27:37.460 | you said is the title, correct?

01:27:38.900 | - Yeah, "Determined," the science of life without free will.

01:27:42.980 | Seems like you can't publish a book these days

01:27:44.960 | without a subtitle, so that's it.

01:27:48.660 | - Fantastic.

01:27:49.740 | Well, very excited to read the book.

01:27:52.340 | Very grateful to you for this conversation today.

01:27:54.740 | I learned a ton.

01:27:56.620 | Every time you speak, I learn.

01:27:58.100 | And for me, it's really been a pleasure

01:28:00.020 | and a delight to interact with you today

01:28:02.440 | and over the previous years, I should say, as colleagues.

01:28:07.040 | And thank you again, Robert, for everything that you do

01:28:10.840 | and all the hard, hard work and thinking

01:28:12.700 | that you put into your work,

01:28:13.740 | because it's clear that you put a lot of hard work

01:28:16.780 | and thinking and we all benefit as a consequence.

01:28:21.100 | Thanks and thanks for having me.

01:28:24.020 | This was a blast.

01:28:25.220 | - Thank you for joining me for my conversation

01:28:28.500 | with Dr. Robert Sapolsky.

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Dr. Robert Sapolsky: Science of Stress, Testosterone & Free Will | Huberman Lab Podcast #35

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