back to indexDr. Robert Sapolsky: Science of Stress, Testosterone & Free Will | Huberman Lab Podcast #35
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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman, and I'm a professor of neurobiology
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and ophthalmology at Stanford School of Medicine.
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Today, I have the pleasure of introducing
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Dr. Robert Sapolsky.
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Dr. Sapolsky is a professor of biology and neurosurgery
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at Stanford University.
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His laboratory has worked on a large variety of topics,
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including stress, hormones, including testosterone
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and estrogen, and how the different members
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of a given species interact according to factors
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like hormones, hierarchy within primate troops,
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and how things like stress, reproduction,
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and competition impact behavior.
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One of the things that makes Dr. Sapolsky's work so unique
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is that it combines elements from primatology,
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including field studies, with human behavior,
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in essence, trying to unveil how humans
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as old world primates are controlled by different elements
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of our biology, as well as our psychology.
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Dr. Sapolsky is also a prolific author of popular books,
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such as Why Zebras Don't Get Ulcers,
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The Trouble with Testosterone,
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and Behave the Biology of Humans at Our Best and Worst.
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During the course of our discussion today,
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Robert also revealed to me that he is close
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to completing a new book entitled
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Determined, The Science of Life Without Free Will.
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And indeed, we discuss the science of life
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without free will during this episode.
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We also discuss stress and how best to control stress
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and how stress controls us at both conscious
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and subconscious levels.
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We talk about testosterone and estrogen
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and hormone replacement therapy
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and how those impact our mind, our psychology,
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and our interactions with others.
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As with any discussion with Dr. Sapolsky,
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we learn about scientific mechanisms
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that make us who we are.
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And today we also discuss tools
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and how we can leverage those scientific mechanisms
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in order to be better versions of ourselves.
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I should mention that unlike most guest interviews
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on the Huberman Lab podcast,
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this one had to be carried out remotely
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due to various constraints.
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So you may hear the occasional audio artifact.
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Please excuse that.
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We felt that the value of a conversation
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with Dr. Sapolsky was well worth those minor, minor glitches
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and indeed the information that he delivers us
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is tremendously valuable, interesting,
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and in many cases, actionable as well.
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Before we begin, I'd like to emphasize that this podcast
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is separate from my teaching and research roles at Stanford.
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It is however, part of my desire and effort
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to bring zero cost to consumer information about science
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and science-related tools to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Our first sponsor is Roca.
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Roca makes sunglasses and eyeglasses
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that are of the absolute highest quality.
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The company was founded by two all-American swimmers
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from Stanford and everything about the design
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There are several things I like about Roca glasses so much.
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One of them is that the aesthetic of the glasses is great.
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The aesthetic of them is really terrific
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And that's absolutely essential.
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If you'd like to try Roca glasses,
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you can go to roca.com and enter the code Huberman
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That's R-O-K-A.com and enter the code Huberman at checkout.
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Today's podcast is also brought to us by Inside Tracker.
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Inside Tracker is a personalized nutrition platform
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that analyzes data from your blood and DNA
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and now with the advent of quality DNA tests,
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The reason I'm such a fan of getting blood work done
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you can go to insidetracker.com slash Huberman
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Just use the code Huberman at checkout.
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Today's podcast is also brought to us by Belcampo.
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Belcampo is a regenerative farm in Northern California
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that raises organic, grass-fed,
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and finished certified humane meats.
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I eat meat about once a day.
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In general, my lunch or my breakfast consists of some meat
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and that meat has to be a very high quality,
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and generally I'll eat some vegetable as well.
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And then I tend to eat pastas and rice
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and things of that sort later in the day or in the evening
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in order to facilitate the transition to sleep.
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So I'm eating meat about once a day,
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and I always insist that the meat that I eat
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and that the animals were raised and maintained humanely.
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I'm partial to the ribeyes or the New York steaks.
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So on one day I might have a ribeye,
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the next day I might have a New York steak.
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I also really like the meatballs.
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I'm a particular fan of the meatballs.
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and enter the code Huberman at checkout
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And now without further ado,
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my conversation with Dr. Robert Sapolsky.
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Great, well, thank you so much, Robert,
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for joining us today.
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I've been looking forward to this for a very long time.
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I'm glad to be here.
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There's an enormous range of topics
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that we could drill into,
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but just to start off,
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I want to return to a topic that is near and dear
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to your heart, which is stress.
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And one of the questions that I get most commonly
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is what is the difference between short and long-term stress
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in terms of their benefits and their drawbacks?
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And the reason I say benefits is that obviously stress
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and the stress response can keep us alive,
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but stress of course can also sharpen our mental acuity
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and things of that sort.
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So how should we conceptualize stress
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and how should we conceptualize stress
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in the short term and in the long term?
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Well, basically sort of two graphs that one would draw.
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The first one is just all sorts
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of beneficial effects of stress short term.
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And then once we get into the chronicity,
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it's just downhill from there.
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Short term because it saves you from the predator.
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Short term because you're giving a presentation
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and you think more clearly,
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or your focus is better, all sorts of aspects of that.
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And what then winds up being an argument
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is how long does it take to go from short term to long term?
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And that's somewhat arbitrary,
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but the sorts of chronic stressors
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that most people deal with are just undeniably
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in the chronic range,
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like having spent the last 20 years, daily traffic jams
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or abusive boss or some such thing.
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The other curve that's sort of perpendicular to this
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is dealing with the fact
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that sometimes stress is a great thing.
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Like our goal is not to cure people of stress
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because if it's the right kind, we love it.
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We pay good money to be stressed that way
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by a scary movie or roller coaster ride.
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What you wind up seeing is
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when it's the right amount of stress,
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it's what we call stimulation.
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And the basic curve there is here's an optimal level
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of stimulation and too little and function goes down
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with what we would call boredom and too much
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and function goes down with what we would call stress.
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And the optimum is what all of us aim for.
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In terms of the benefits of stress in the short term,
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one thing that's really striking to me is
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how physiologically the stress response
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looks so much like the excitement response
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to a positive event.
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And we can speculate that the fundamental difference
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between short-term stress and short-term excitement
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is some neuromodulator like dopamine
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or something like that.
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But is there anything else that we know about the biology
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that reveals to us what really creates this thing
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we call valence that an experience can be terrible
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or feel awful, or it can feel wonderful, exhilarating
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depending on this somewhat subjective feature
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Do we know what valence is or where it resides?
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On a really mechanical level,
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if you're in a circumstance that is requiring
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that your heart races and you're breathing as fast
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and you're using your muscles and some such thing,
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you're going to be having roughly
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the same brain activation profile,
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whether this is for something wonderful
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or something terrible with the one exception being
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that if the amygdala is part of the activation,
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this is something that's going to be counting as adverse.
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Whether that's the circumstance, an adverse circumstance
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recruiting the amygdala into it
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and how much it's the amygdala being involved
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biases you towards interpreting it as even more awful.
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The amygdala in some ways is kind of the checkpoint
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as to whether we're talking about excitement or terror.
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Let's use the amygdala as a transition point
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to another topic that you've spent many years working on
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and thinking about, which is testosterone
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and other sex steroid hormones.
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I heard you say once before that
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among all the brain areas that bind testosterone,
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that where testosterone can park and create effects
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that the amygdala is among the most chock-a-block full
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of these parking spots, these receptors.
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I realize there's a lot here,
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but how should we think about the role of testosterone
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in the amygdala given that the engagement of the amygdala
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is fundamental in this transition point
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between a exhilarating positive response
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and a negative stressful response?
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Or maybe just broadly,
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how should we think about testosterone
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and its effects on the brain?
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And pertinent to the transition
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from whether this is a stressor that's evoking fear
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or evoking aggression in terms of that continuum also
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because the amygdala is in the center
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of all four points on those axes.
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Basically almost everybody out there
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has a completely wrong idea as to what testosterone does,
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which is testosterone makes you aggressive
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because males, virtually every species out there
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have more testosterone and are more aggressive
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and seasonal maters have testosterone
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surging at the time of year.
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They're punching it out over territory
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and you take testosterone out of the picture.
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You castrate any mammal out there, including us,
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and levels of aggression will go down.
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And the easy thing then is to conclude
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that testosterone causes aggression.
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And the reality is testosterone does no such thing.
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It doesn't cause aggression.
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And you can see this both behaviorally and in the amygdala.
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What does testosterone do?
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It lowers the threshold for the sort of things
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that would normally provoke you into being aggressive
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so that it happens more easily.
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It makes systems that are already turned on
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turn on louder rather than turning on aggressive music
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or some such thing.
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What does that look like behaviorally?
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You take five male monkeys, put them together,
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they form a dominance hierarchy.
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Number one is great, number five is miserable,
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number three is right in between.
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Now take number three and shoot the guy up
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with tons of testosterone
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and he's gonna be involved in more fights.
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Aha, testosterone uniformly causes aggression.
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But you look closely and there's a pattern to it.
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Is number three now challenging numbers two and one
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for their place in the hierarchy?
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He is brown nosing them exactly as much as he used to.
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What's going on is he's just a miserable terror
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to poor number four and five.
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And in that case, what testosterone is doing
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is amplifying the preexisting patterns of aggression,
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amplifying the social learning that's already gone into it.
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Now on sort of the more reductive level,
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so how does that translate into the amygdala?
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Does testosterone make amigdolloid neurons
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have action potentials?
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Does it cause those neurons to suddenly speak
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about fear and aggression spontaneously?
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What they do is if the amygdala is already being stimulated,
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it increases the rate of neuronal firing.
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What it's worth, it shortens after hyperpolarizations.
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So the theme there exactly is it's not creating aggression,
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it's just upping the volume
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of whatever aggression is already there.
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And once you factor that in,
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it's impossible to say anything about what testosterone does
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outside the context of what testosterone-related behaviors,
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how they get treated in your social settings.
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Yeah, and in terms of status
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and the relationship between individuals,
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either non-human primates or humans,
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can we say that testosterone and levels of testosterone,
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or I should say, can we say that relative levels
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of testosterone between individuals
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is correlated to status within the hierarchy?
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Yes, but in a way that winds up
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being totally uninteresting.
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Like you go back, I don't know,
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whatever number of decades to endocrinology texts,
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and there were two totally reliable findings in there.
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Let's see, I have a dog in here that's so good.
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We like dogs at the Huberman Lab podcast.
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He's jingling a bit.
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They are absolutely welcome, yeah.
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And there'd be two truisms,
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which is higher levels of testosterone
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predict higher levels of aggression
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in humans and other animals.
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Higher levels of testosterone
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predict higher levels of sexual activity.
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Whoa, testosterone causing both.
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And the correlation is there.
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And when you look closely, we've got cause and effect stuff.
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Sexual behavior raises testosterone levels.
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Aggression raises testosterone levels.
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Your levels beforehand are barely predictive
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of what's going to happen.
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So it's a response rather than a cause.
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When you look at that, though,
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in terms of making sense of individual differences,
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they don't matter a whole lot.
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You can spend an entire career on the social circumstances
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that produce 3.5% more testosterone in the circulation
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and expect to see all sorts of interesting implications.
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And that's not really the case.
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It's somewhat of a yes or no modulator
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of the much more subtle social stuff that's already there.
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You know, I think that there are a lot of misconceptions
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about human biology,
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but testosterone seems to be one area
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where at least from what I can find on the internet,
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there's a sort of at the peak of misunderstanding.
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Maybe we could just ask a few more questions
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about testosterone and sexual behavior,
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because there's an interesting story there
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about castration versus non-castration
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and the causality again.
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But before you address that,
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I just want to highlight something that you said
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that I think is so vital,
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which is that behaviors such as aggressive behaviors
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and sexual behaviors can actually increase testosterone.
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Did I hear that correctly?
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And the reverse is sort of true,
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but not in a causal way.
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The opposite direction with the causality, yeah.
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Yeah, so if I were to increase somebody's testosterone
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by 30% male or female, doesn't matter,
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their sexual behavior may or may not change.
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Essentially zero effect at all.
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Your brain is not that sensitive to fluctuations
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in testosterone levels.
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In terms of things like aggression,
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raising testosterone just is a great footnote.
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If you have the right type of willing to die
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in the trenches devotion sort of thing,
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watching your favorite team play a sport
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will raise your testosterone levels
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as you sit there with a potato chips in your arm chair.
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So it's not the physicality of aggression,
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it's the psychological framing of it.
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So yeah, testosterone is not causing that.
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And a great way to appreciate that is,
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okay, so you had all these
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testosterone sexual behavior correlations
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and you do the definitive endocrine intervention,
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which is you do a subtraction study,
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you've removed the testes.
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And as I said before, levels of sexual behavior goes down.
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Good, we've just shown that testosterone
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is somehow causative.
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Critically, they go down, but not down to zero,
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whether you are a rat or a monkey or a human, whatever.
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And what predicts how much residual sexual behavior is there,
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how much sexual behavior there was before castration.
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What that's telling you is by then,
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that's behavior that's being carried by social learning
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in context, rather than by a hormone, exact same thing
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with aggression, drops after castration, doesn't go to zero.
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The more prior history of it,
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the more it just keeps coasting along on its own,
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even without testosterone.
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Very interesting, can we say that there's an exception
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in terms of the early organizing effects of hormones?
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Like for instance, if a developing animal is deprived
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of testosterone or estrogen or aromatized testosterone
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into estrogen, there's a whole story there, as you know.
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But then I could imagine that the circuits of the brain
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that are responsible for initiating sexual behavior
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in the first place might not emerge
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and therefore not be sensitive to testosterone later in life.
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And a great way of seeing that is this totally nutty
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biological factoid, which is the second
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to fourth digit ratio in hands.
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Totally obscure thing.
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The ratio of one to the other in some way
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reflects levels of testosterone androgen exposure
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during fetal life.
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And I can't remember which way it goes
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and it's minuscule and you need a thousand people
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in your sample size to be able to see anything,
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but you see it in other primates.
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It's already there in fetal, sonograms, all of that.
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So that's a readout of subtle differences
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in prenatal exposure.
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And that winds up being a predictor
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of a whole range of subtle stuff in adult behavior.
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So yeah, at the fetal end,
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when you're still building everything,
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testosterone and the amount of it
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is making a huge difference.
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By the time you're an adult,
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it's just somewhat of an all or none signal.
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I have a confession,
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which is that I was a master's student at Berkeley
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in Mark Breedlove's arena.
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So I'm an author on that paper,
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although I'm deep within the author line
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and you got the description of it exactly right,
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that it's the D two,
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the index finger to the ring finger ratio
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is more similar in females
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and then it is in males and males,
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the index finger tends to be shorter.
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And for people out there who are listening to this,
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who are now freaking out or measuring,
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there's a proper way to measure this,
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which is eyeballing it doesn't work all the time
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unless at the extremes.
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And there's some more interesting stories there.
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It actually has been replicated
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no fewer than five times, Mark Breedlove tells me.
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But yes, in terms of these early organizing effects,
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those seem very robust in most studies.
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These later effects are a sort of activation
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of neural circuits by hormones.
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I'm absolutely fascinated by this.
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And I do have a couple other questions,
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which is we normally associate testosterone with males,
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but of course, females make testosterone as well
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from the adrenals and presumably elsewhere too.
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I'm guessing if we looked hard enough,
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we'd probably find that there were other sources
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of androgens in females.
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Can we say that these general contours of effects
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on aggression also pertain to females?
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And I suppose I should ask in particular
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about female-female aggression,
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which does exist in many species,
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female-male to aggression, as well as maternal aggression,
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which is a robust aspect of our evolution, of course,
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that the mother will, an angry mother animal of any kind
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protecting her young is truly dangerous
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in the best sense of the word.
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And that type of post-parturition period
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after birth aggression is all about estrogen,
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progesterone, those sorts of things.
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Female aggression the rest of the time
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has testosterone as a major player
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at a much lower level on the average,
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on the average, one always has to say,
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but it's basically the same punchlines.
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In females, the lower levels of testosterone
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are essential for typical levels of aggression
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and sexual behavior.
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None of us, they're not causing it.
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It's not sensitive to small individual differences.
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You can get way over impressed
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with the importance of androgens in females
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just as readily as in males.
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So in line with that,
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how should we conceptualize testosterone?
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I realize there isn't a single sentence
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or that can capture a hormone and all its effects
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because hormones have so many different slow
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and fast effects on the brain, on other glands,
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on their own, on the very glands that produce them.
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But as I've heard you talk about testosterone today
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and over the years, I start to get the impression
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that as the most misunderstood molecule
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in human health in the universe,
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it has, it's clearly doing something very powerful.
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It's shifting the way that certain neural circuits work,
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adjusting the gain on the amygdala as you described
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and certainly other things as well.
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Is there any truism about testosterone
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and its relationship to effort
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or its relationship to resilience
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and in a way that maybe will help me and other people
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sort of think about how to think about testosterone?
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Yeah, maybe three separate answers to that.
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The first one is I think it's a fair summary
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to think that when it comes to motivated strong behaviors,
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what testosterone does is make you more
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of whatever you already are in that domain.
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Sexual arousal, libido, aggressiveness,
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spontaneous aggression, reactive aggression,
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things of that sort.
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It's upping the volume of things
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that are already strongly there.
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Second way to think about it is,
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well, here's like my favorite finding about testosterone.
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And this was some wonderful work by a guy, John Wingfield,
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who's one of the best behavioral endocrinologists
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out there, and about 20 years ago,
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he formulated what was called the challenge hypothesis
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of testosterone action.
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What does testosterone do?
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Testosterone is what you secrete
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when your status is being challenged
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and it makes it more likely that you'll do the behaviors
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needed to hold onto your status.
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Okay, so that's totally boringly straightforward
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if you're a baboon.
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If somebody is challenging your high rank,
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the appropriate response on your part
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is going to be aggression.
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All right, so we've just gotten through the back door
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of testosterone and aggression again.
link |
But then you get to humans,
link |
and humans have lots of different ways
link |
of achieving or maintaining status.
link |
And all you need to do is go to like some fancy
link |
private school's annual auction,
link |
and you will see all these half-drunk alpha males
link |
competing to see who can give the most money away
link |
as a show of conspicuous like, you know,
link |
property that they have.
link |
And in a setting like that, I mean,
link |
I haven't been able to take urine samples
link |
at those times, unfortunately,
link |
but that shows the flip side of it.
link |
If you have a species that hands out status
link |
in a very different sort of way,
link |
testosterone is going to boost that also.
link |
Okay, so that generates a totally nutty prediction.
link |
Wow, take people in a circumstance,
link |
say playing an economic game,
link |
where you get status by being trustworthy
link |
and being generous in your interactions with the game.
link |
If you give people testosterone,
link |
does that make them more generous?
link |
And that's absolutely the case.
link |
Totally cool finding.
link |
Showing you, I don't know,
link |
basically if you took a whole bunch of Buddhist monks
link |
and shot them up with testosterone,
link |
they'd get all competitive with each other
link |
as to who could do the most random acts of kindness.
link |
And if we have a societal problem with too much aggression,
link |
the first culprit to look at is not testosterone.
link |
The first to look at is that we hand out
link |
so much damn elevated status for aggression
link |
in so many circumstances.
link |
So I find that finding to be fantastic.
link |
Third thing about subtlety of testosterone.
link |
Okay, so like some subtler behavioral effects,
link |
you give testosterone to people
link |
and they become more confident.
link |
They become more self-confident.
link |
Well, that's good.
link |
People pay to take all sorts of nonsensical self-help courses
link |
that will boost your self-esteem.
link |
And that's a good thing.
link |
Unless testosterone makes you more confident,
link |
that is inaccurate.
link |
And you're more likely to barrel into wrong decisions.
link |
What's shown in economic gameplay
link |
is that testosterone by making you more confident
link |
makes you less cooperative.
link |
Because who needs to cooperate
link |
because I'm on top of this all on my own.
link |
Testosterone makes people cocky and impulsive.
link |
And that may be great in one setting,
link |
but if in the other is you're absolutely sure
link |
your army is gonna overrun the other country in three days.
link |
So hell, let's start World War I
link |
and you get a big surprise out of it.
link |
Testosterone altering risk assessment beforehand
link |
probably played a big role in that kind of miscalculation.
link |
Super interesting.
link |
I always think about testosterone and dopamine
link |
being close cousins in the brain,
link |
not just because of their relationship
link |
through the pituitary and hypothalamus, that of course,
link |
but also because of dopamine's salient role
link |
in creating this bias towards exteroception.
link |
When somebody takes a drug that increases dopamine
link |
or they're chock-a-block full of dopamine,
link |
they tend, I want to highlight tend
link |
because I'm really generalizing it,
link |
but they tend to focus on outward goals,
link |
things beyond the boundaries of their skin.
link |
And testosterone seems to do a bit of the same.
link |
It tends to put us into a similar mode
link |
of perceiving the outside world
link |
in ways that we're asking questions like,
link |
how do I relate to this other of my species?
link |
How do I relate to these goals?
link |
Is there anything that we can do
link |
to better conceptualize the relationship
link |
between testosterone and dopamine and motivation?
link |
Or would that just take us down the alleyways
link |
of neural pathways and the hypothalamus,
link |
which was fine too.
link |
Well, I think it's got lots to do
link |
with sort of this massive revisionism about dopamine.
link |
Everyone since the pharaohs got brought up
link |
being taught that dopamine is about pleasure and reward.
link |
It turns out it isn't.
link |
It's about anticipation of reward.
link |
And it's about generating the motivation,
link |
the goal-directed behavior needed to go get that reward.
link |
And before you know it,
link |
you're using like elevated dopamine your entire life
link |
to motivate you to do whatever's going to get you
link |
like entry into heaven after life.
link |
Kind of, you know, it's doing that sort of thing.
link |
So it's really about the motivation.
link |
And what testosterone does,
link |
even in individuals who are not aggressive
link |
and why testosterone replacement
link |
is often a very helpful thing for aging males,
link |
is it increases energy.
link |
It increases a sense of there-ness,
link |
of presence of alertness.
link |
It increases motivation.
link |
So that's a whole aspect which then takes us into
link |
is your motivation to get up and like go,
link |
you know, hand out lots of soup
link |
in a soup kitchen for homeless people?
link |
Or is it to get up and go ethnically cleanse a village?
link |
It's got much to do with what your makeup was
link |
before the testosterone got on board.
link |
So it's activating in an energetic sense,
link |
testosterone within minutes
link |
increases glucose uptake into skeletal muscle.
link |
You're just more awake and alert and all of that.
link |
And that has a lot to do with what dopamine does.
link |
And as one might predict then,
link |
getting just the right levels of testosterone
link |
infused into your bloodstream feels great to lab rats.
link |
They will lever press to get infused into the range
link |
that optimizes dopamine release.
link |
So you're absolutely right.
link |
They're deeply intertwined.
link |
Yeah, such beautiful biology there.
link |
I love the way you encapsulate their relationship.
link |
I want to ask about estrogen.
link |
We don't hear about estrogen as often.
link |
And it's always interesting to me now
link |
doing some public facing education, you know,
link |
that testosterone is this very controversial molecule.
link |
Just to say it is almost controversial.
link |
But estrogen doesn't seem to hold
link |
the same controversial weight.
link |
And yet estrogen has some very powerful effects
link |
on both the animal brain and on the human brain
link |
of males and females.
link |
Men do not want their estrogen to go too low.
link |
Terrible things happen.
link |
They will lose cognitive function.
link |
So men need estrogen as well.
link |
But perhaps maybe we can put the same filter on estrogen
link |
as we did on testosterone.
link |
Are there any general themes of estrogen
link |
that people should be aware of
link |
or that you think that are generally misunderstood?
link |
Is it really all about feelings and empathy
link |
and making us more sensitive?
link |
No, and it's once again, very context dependent.
link |
And if estrogen after giving birth
link |
is playing a central role in you wanting to shred the face
link |
of somebody getting too close to your kittens kind of thing,
link |
we know it's not just warm, fuzzy, empathic kind of stuff.
link |
Estrogen in lots of ways could be summarized by
link |
if you had a choice in the matter
link |
between having a lot of estrogen in your bloodstream or not,
link |
go for having a lot of estrogen.
link |
It enhances cognition exactly as you said.
link |
It stimulates neurogenesis in the hippocampus.
link |
It increases glucose and oxygen delivery.
link |
It protects you from dementia.
link |
It decreases inflammatory oxidative damage
link |
to blood vessels, which is why it's good
link |
for protecting from cardiovascular disease
link |
in contrast to testosterone,
link |
which is making every one of those things worse.
link |
This brings up this minefield of the question,
link |
which is so what about post-menopausal estrogen?
link |
And all sorts of lab studies with non-human primates
link |
suggested that you keep estrogen levels high
link |
after a monkey's equivalent of menopause
link |
and you're gonna keep brain health a lot better,
link |
decreasing the risk of dementia, stroke, every such thing.
link |
Estrogen is a great antioxidant, all of that.
link |
So in the nineties, I think when Healy,
link |
I'm forgetting her name,
link |
but when there was the first female head of the NIH,
link |
Bernadette Healy, set up this massive prospective
link |
human study, what was gonna be the biggest one of all times,
link |
looking at the pluses and minuses
link |
of post-menopausal estrogen.
link |
And tens of thousands of women, and this was gonna be,
link |
and they had to cut the study short
link |
because what they were seeing was estrogen
link |
was not only doing the normal bad stuff that you expect
link |
in terms of some decalcification stuff,
link |
but it was increasing the risk of cardiovascular disease.
link |
And it was increasing the risk of stroke
link |
and it was increasing the risk of dementia.
link |
And this ground to a halt and everybody,
link |
they stopped the study in front page news
link |
and everybody had that point.
link |
And nobody could make sense of it,
link |
who had been spending the last 20 years
link |
studying the exact same thing in primates
link |
and seeing all the protective effects.
link |
And the explanation turned out to be one of those things
link |
where like law of unexpected consequences.
link |
Okay, menopause in women that last different lengths of time
link |
that may be a factor that's gonna come.
link |
Let's not start giving our study subjects more estrogen
link |
until they're totally past menopause.
link |
And when you've got that lag time in between,
link |
you shift all sorts of estrogen receptor patterns
link |
and that's where all of the bad effects come from.
link |
All of the monkey studies had involved
link |
just maintaining ovulatory levels
link |
into the post-menopausal period.
link |
And you do that and you get great effects.
link |
Estrogen is one of the greatest predictors
link |
of protection from Alzheimer's disease, all of that,
link |
but it needs to be physiological.
link |
Just keep continuing what your body has been doing
link |
for a long time versus let the whole thing shut down
link |
and suddenly like try to fire up the coal stoves
link |
at the bottom of the basement kind of thing
link |
and get that going.
link |
There you get utterly different outcomes.
link |
And that caused a lot of human health consequences
link |
when people suddenly decided that estrogen
link |
is in fact neurologically endangering post-menopausal A.
link |
Wow, that's fascinating.
link |
And I never thought that these steroid hormone receptors
link |
could, you know, by not binding estrogen,
link |
being devoid of estrogen binding, I should say,
link |
could then set off opposite biochemical cascades.
link |
I guess it raises the question
link |
about testosterone replacement too,
link |
whether or not people should talk to their doctor
link |
Men and women talk to your physicians before too long
link |
to avoid these, whatever is happening in these periods
link |
where there isn't sufficient testosterone and or estrogen.
link |
It sounds like it could cause longer term problems
link |
even when therapies are introduced.
link |
Two additional misery slash complications.
link |
So, okay, you're trying to understand,
link |
you look at women with a history
link |
with or without post-menopausal estrogen replacement
link |
where it's done right.
link |
And you're seeing 20 years later,
link |
estrogen is a predictor of a decreased risk of Alzheimer's.
link |
Then you got to start trying to do
link |
the unpacking prospective type studies.
link |
How much estrogen?
link |
Estrogen is just a catch-all term for a bunch of hormones,
link |
estrone, estradiol, estriol.
link |
How much of each one of them?
link |
Natural or synthetic?
link |
Go try to figure all of that out.
link |
And the second complication is,
link |
it's often hard to say anything about what estrogen does,
link |
outside the context of what progesterone is doing.
link |
And often it's not the absolute levels of either,
link |
it's the ratio of the two.
link |
This is such a more complicated endocrine system
link |
than testosterone.
link |
because you have to generate dramatic cyclicity
link |
that like no male hypothalamus ever has to dream of.
link |
It's a much, much more complicated system.
link |
Thus, it's more complicated to understand
link |
let alone like figure out what the ideal benefits are of it.
link |
I don't know what to make of the literature
link |
on dropping rates of testosterone
link |
and endocrine disruptors.
link |
You know, I was at Berkeley when Tyrone Hayes
link |
published his data on these frogs
link |
that were drinking water from various locations
link |
throughout the United States, not just in California,
link |
and seeing very severe endocrine disruption
link |
through blockade and of androgen receptors
link |
and all sorts of issues.
link |
And you hear this all the time now
link |
that sperm counts are dropping,
link |
that there are all these endocrine disruptors,
link |
that there's birth control in the water,
link |
in the drinking water.
link |
It all starts to sound a little crazy.
link |
And yet I've also been fooled before by, you know,
link |
I guess a good example would be
link |
there's a lot of crazy stuff in the world online
link |
about all the terrible stuff in highly processed foods.
link |
And yet you've got very respectable people,
link |
endocrinologists at UCSF, like Robert Lustig saying,
link |
yeah, these, a lot of these hidden sugars
link |
and these emulsifiers, they're causing real problems.
link |
So I've become more open-minded about the question.
link |
And so are we suffering from drops in sperm counts
link |
and testosterone and estrogen and fertility
link |
as a consequence of endocrine disruptors
link |
in the environments and food,
link |
or because of social reasons?
link |
Is there anything that we can hang our hat on,
link |
like real data that you're confident in,
link |
or is it just a mess?
link |
No, the phenomenon does appear to be quite real.
link |
Cross-sectional studies, human populations,
link |
or I still don't understand why this was one
link |
of the first things that Hayes spotted,
link |
decreasing testicle size in crocodiles.
link |
Go figure why that was one of the first contributions
link |
And I think the phenomenon is absolutely real.
link |
And what you're then left with is two classic challenges,
link |
which is this is correlated with something broad,
link |
environmental toxins, which ones, how much, when, et cetera.
link |
And the other one always being, well, okay, dropping.
link |
Is it dropping enough to make a difference?
link |
How big of an effect is this?
link |
And those are where the juries are still out.
link |
Yeah, it's an area that I know
link |
there's a lot of interest in.
link |
And you've got groups of people who won't touch a receipt
link |
at a store because of the BPAs that are on the inks of the,
link |
and then you've got people who don't care about those things.
link |
It is a fascinating area.
link |
And I hope that more biology will be done there soon.
link |
I'd like to briefly return to stress.
link |
You described a study once about two rats,
link |
one running on a wheel voluntarily,
link |
one who's basically stuck in a running wheel
link |
and is forced to run anytime rat number one runs.
link |
So in one case, the rat is voluntarily exercising.
link |
And in the other case,
link |
the rat is being forced to go to PE class, so to speak,
link |
but really, and seeing divergent effects on biology.
link |
And I'd like to just touch into this
link |
and use it as kind of a case study
link |
for stress mitigation in general.
link |
I'm rather obsessed in our colleague, David Spiegel,
link |
associate chair of psychiatry at Stanford
link |
is obsessed with this question
link |
of how humans can start to mitigate their own stress.
link |
What do you think about stress mitigation
link |
and what should we do as individuals and as families
link |
and as a culture to try and encourage people
link |
to mitigate their stress,
link |
but in ways that are not going to turn us
link |
into rat number two,
link |
where we're being forced to mitigate our own stress
link |
and therefore becomes more stressful?
link |
And what you see is rat number one
link |
gets all the benefits of exercise.
link |
Rat number two gets all the downsides of severe stress
link |
with the same exact muscle expenditure
link |
and movements going on, perfectly yoked,
link |
great example that it's the interpretation in your head.
link |
And I haven't kept up with that literature,
link |
but I'll bet you rat number two
link |
is having a whole lot more activity
link |
in its amygdala than is rat number one.
link |
Okay, so stress mitigation.
link |
Anything I should say here,
link |
I should preface with I'm reasonably good
link |
at telling people what's going to happen
link |
if they don't manage their stress,
link |
but I'm terrible at actually like managing stress
link |
or advising how to manage it.
link |
I'm much better with the bad news aspect of it.
link |
But what do you see is by now,
link |
just a classic literature, half a century old,
link |
sort of showing what are the building blocks of stress.
link |
Not, ooh, you step outside
link |
and you've been gored by an elephant
link |
and can you grow from your experience
link |
and what doesn't kill you makes you stronger.
link |
You could have a stress response,
link |
but you're in the realm of the gray zone
link |
of ambiguous social interactions, that sort of thing.
link |
Some people have massive stress responses,
link |
others not at all in between, enjoy it.
link |
Like what are the building blocks
link |
of what makes psychological stress stressful?
link |
And the first one is exactly what is brought up
link |
by that running study.
link |
Do you have a sense of control?
link |
A sense of control makes stressors less stressful.
link |
And the running wheel shows that or studies where you,
link |
you lab rat or you college freshmen volunteer
link |
have been trained that by pressing a lever,
link |
you're less likely to get a shock.
link |
And today you're at the lever,
link |
they're working away and unbeknownst to you,
link |
the lever has been turned off
link |
and it has no effect on shock frequency,
link |
but because you think you have some control,
link |
you have less of a stress response.
link |
If you were a rat and doing this day in and day out,
link |
you're less likely to get an ulcer.
link |
So a sense of control.
link |
Related to that is a sense of predictability.
link |
Rat gets shocked, human gets shocked, whatever.
link |
And the scenario either is the shocks come now and then,
link |
or the shocks come now and then,
link |
and 10 seconds before a little warning light comes on.
link |
And when you get the warning light,
link |
the shocks aren't as stressful.
link |
You got predictability
link |
because if you're not getting warning lights,
link |
any second you could be a half second away
link |
from the next shock, you get a warning light
link |
and you know that if there isn't one,
link |
you've got at least 10 seconds worth of relaxation.
link |
You know what's coming, you can prepare
link |
your coping responses and best of all,
link |
afterward, you know when you're finally safe,
link |
when you can recover from it.
link |
And that's enormously protective.
link |
Others, outlet for frustration.
link |
You take a rat who's getting shocked
link |
and if it could run on a running wheel,
link |
that's a protective thing if it's doing it voluntarily.
link |
If you've got a rat and it can gnaw on a bar of wood,
link |
a stressor is less stressful.
link |
Unfortunately, if you have a rat or primate or human
link |
and they're stressed, the ability to aggressively dump
link |
on somebody smaller and weaker
link |
also reduces the stress response
link |
and displacement aggression,
link |
and the fact that displacement aggression reduces stress
link |
accounts for a huge percentage of Earth's unhappiness.
link |
So all of those variables get social support as well.
link |
That's a good one, interpreting circumstances
link |
as being good news rather than bad.
link |
Hooray, so you've got this very simple
link |
sort of like take home recipe of go out
link |
and get as much control and as much predictability
link |
and as many outlets and as much social support as possible,
link |
and you're gonna do just fine.
link |
And you go out and do that
link |
and that's a recipe for total disaster,
link |
because it's much, much more subtle than that.
link |
One great example.
link |
Okay, so you're getting shocked.
link |
You want a warning beforehand.
link |
Get a little warning light 10 seconds before each shock.
link |
It's wonderfully protective.
link |
Get a warning light one second before the shock.
link |
Doesn't do anything.
link |
There's not enough time for you
link |
to get the psychological benefits of the anticipation.
link |
Now instead, get the little warning coming on
link |
two minutes before each shock,
link |
and it's gonna make things worse,
link |
because you're not gonna be sitting there
link |
like reveling in sort of your sense of predictability
link |
and it's soon gonna be over.
link |
You're gonna be sitting there for two minutes saying,
link |
damn, here it comes.
link |
Predictive information only works in a narrow domain.
link |
Similarly, control.
link |
Do you wanna have a sense of control in the face of stress?
link |
And the answer is only if it is a mild to moderate stressor,
link |
because what's happening then,
link |
your sense of control is completely independent
link |
of the reality of whether you have control or not.
link |
But in the face of mild to moderate stressors,
link |
a sense of control gets interpreted as,
link |
wow, look how much worse things could have been.
link |
Thank God I have control.
link |
I'm on top of this to master my fate.
link |
In contrast, if it's a major stressor,
link |
all that a arbitrary sense of control does
link |
is make you think, oh my God,
link |
look how much better it could have been.
link |
I could have prevented it.
link |
And we all know that intuitively,
link |
like we do that in the face of people's worst stressors.
link |
Nobody could have stopped the car
link |
the way the kids suddenly jumped out.
link |
It wouldn't have mattered if you had gotten them
link |
to the doctor a month ago instead of now,
link |
it wouldn't have made me,
link |
you didn't actually have any control.
link |
And what you see is you absolutely want to have
link |
a huge sense of control over mild to moderate stressors
link |
and especially ones that result in a good outcome.
link |
And in the face of horrible stressors,
link |
what you want to do is like self-deception
link |
and like truth and beauty don't necessarily
link |
go hand in hand at that point.
link |
And that's why stress management techniques
link |
about control and predictability
link |
wind up being far worse than neutral
link |
if you're preaching that to somebody homeless
link |
or somebody with terminal cancer
link |
or somebody who's a refugee,
link |
tell a neurotic middle-class person
link |
that they have the psychological tools
link |
to turn hell into heaven.
link |
And there's some truth to that.
link |
Do the same thing to somebody
link |
who's going through a real hell
link |
and that's just privileged heartlessness to do that
link |
because that doesn't work.
link |
More and more, you know, outlets,
link |
if your outlets are damaging,
link |
that's not a good way to mitigate stress.
link |
Social support, if you're confusing mere acquaintances
link |
for real social support,
link |
you're going to have the rug pulled out
link |
from under you at some point.
link |
If you're mistaking social support for being,
link |
going and bitching and moaning
link |
and demanding supportiveness from everyone around you,
link |
rather than you doing some of that reciprocally,
link |
that's not going to work very well either.
link |
Well either, you know, it's not simple.
link |
It's not for nothing that lots of us are really lousy
link |
at being good friends and things like that
link |
and why it takes a lot of work to do it right
link |
because you do it wrong
link |
and it may temporarily seem like a great thing,
link |
but when it turns out to be completely misplaced faith,
link |
you're going to be feeling worse than before you started.
link |
These days, there's a lot of interest
link |
in using physical practices to mitigate stress,
link |
you know, trying to get out of the ruminating
link |
and to some extent,
link |
take control of neural circuits in the brain
link |
by using exercise and using breathing and hypnosis.
link |
And of course, hypnosis has a mental component as well.
link |
So what are your thoughts on stress mitigation
link |
from the standpoint of, okay,
link |
so we don't want to be rat number two,
link |
we want to select something for ourselves.
link |
So we have to take the initiative for ourselves,
link |
being forced into exercising is not,
link |
it could actually have negative health effects perhaps.
link |
So we need to pick something that we like,
link |
we need to take control of it.
link |
In terms of supporting other people,
link |
you touched on that a bit,
link |
what is the best way to support other people?
link |
Is it to talk about the stressful thing?
link |
I mean, I'm not asking you to play psychologist here,
link |
but I find divergent data on this.
link |
You know, we can spin ourselves up into a lather
link |
by ruminating on something.
link |
And language seems to me like it's a wonderful tool,
link |
but it's also a fairly deprived tool
link |
because it doesn't really get into the core
link |
of our physiology like something like breathing would.
link |
So what are your thoughts on more, for lack of a better way
link |
to put it, more head-centered cognitive approaches
link |
to stress mitigation versus kind of going
link |
at the core physiology, cold showers now,
link |
or even a thing to some extent, you know,
link |
just to get people stress acclimated,
link |
voluntarily taking cold showers, you know?
link |
That makes some sense physiologically preconditioning
link |
for when the real stressors come.
link |
In terms of what you bring up,
link |
wow, transcendental meditation, mindfulness, exercise,
link |
prayer, sort of reflecting on gratitude,
link |
all that sort of thing.
link |
Collectively, they work on the average.
link |
They work in terms of they can lower heart rate
link |
and cholesterol levels and have all sorts of good outcomes,
link |
but they come with provisos.
link |
One is exactly the caveat that comes out
link |
of the running wheel study is it doesn't matter
link |
how many of your friends swear by this stress management
link |
technique, if doing it makes you want to screen your head
link |
off after 10 seconds,
link |
that's not the one that's going to work for you.
link |
So, you know, read the fine print and the testimonials,
link |
but it's gotta be something that works for you.
link |
Another one is the stress management type techniques
link |
that work, you can't save them for the weekend.
link |
You can't save them for when you're stuck on hold
link |
on the phone with Muzak for two minutes.
link |
It's gotta be something where you stop what you're doing
link |
and do it virtually daily or every other day
link |
and spend 20, 30 minutes doing it.
link |
And what you see coming out of that
link |
is this like 80, 20 rule from economics,
link |
80, 20, 80% of the complaints in the store
link |
come from 20% of the customers, things like that.
link |
What you see is if your entire life consists
link |
of every single thing on your shoulders
link |
that you can't say no to 24 seven,
link |
if you've stopped that and finally said,
link |
my wellbeing is important enough
link |
that I'm finally going to say no to some of the stuff
link |
that I can't say no to,
link |
and I'm going to do it every day for 20 minutes,
link |
whatever stress management technique you then do
link |
in those 20 minutes, short of who knows what,
link |
you're already 80% of the way there
link |
simply by having decided your wellbeing is important enough
link |
that you're going to stop every single day
link |
and have that as priority.
link |
And that's exactly the same finding
link |
that you find people with chronic depression untreated
link |
that merely calling and getting an appointment
link |
to see a mental health professional,
link |
people start feeling better already
link |
because it's evidence that you've been activated
link |
and you matter enough to do this
link |
and you could conceive that this would actually
link |
have a good outcome rather than a hopeless one.
link |
Just doing something meditative or reflective every day
link |
or so, and it hardly even matters which one you're doing.
link |
And what comes out of that is thus another warning,
link |
which is do not trust anybody who says
link |
it has been scientifically proven
link |
that their brand of stress management
link |
works better than the other ones.
link |
Just watch your wallet at that point.
link |
Yeah, amen, I think one of the core goals of my lab
link |
and David Spiegel's lab, and I know you've worked
link |
with David and published papers with David as well,
link |
is to really try and find out what are the various
link |
entry points to this thing that we call
link |
the autonomic nervous system and the stress system
link |
and the systems that when gone unchecked
link |
really can take us down a dark path.
link |
And the idea that there are so many entry points
link |
is really the one that keeps,
link |
what the data keep telling us over and over again.
link |
So there's no magic breathing tool or exercise.
link |
It's any variety of those or one of those.
link |
And again, we come back to this idea
link |
that it's the one that you select
link |
and the one that you make space for,
link |
and it's the one that you hopefully enjoy
link |
that's going to work best in terms of physiology.
link |
And one that's benign for those people
link |
who were stuck around you.
link |
Right, right, absolutely.
link |
And that brings me to this question of I find it amazing
link |
that how we perceive an event
link |
and whether or not we chose to be in that event or not
link |
can have such incredibly different effects
link |
on circuitry of the brain and circuitry of the body
link |
and biology of cells.
link |
And in some ways it boggles my mind,
link |
like how can a decision made presumably
link |
with the prefrontal cortex,
link |
although other parts of the brain as well,
link |
how can that change essentially the polarity
link |
of a response in the body?
link |
And I mean, you've talked before about type A personalities
link |
and we don't have to go into all the detail there
link |
but it is interesting that the effects of endothelial cells,
link |
I mean, literally of the size of the portals for blood
link |
are in opposite direction,
link |
depending on whether or not somebody
link |
wants to be in a situation, is a highly motivated person.
link |
Maybe you could just give us the top contour of that
link |
because I think it really illustrates this principle
link |
And then maybe if you would,
link |
you could just speculate on how the brain might have
link |
this switch to turn one experience from terrible
link |
to beneficial or from beneficial to terrible.
link |
It's really fascinating.
link |
Well, I mean, all you need to do is like tonight
link |
before you're going to sleep and you're lying in bed
link |
and you're nice and drowsy
link |
and your heart's beating nice and slow,
link |
you'll start thinking about the fact that, you know,
link |
that heart isn't going to beat forever.
link |
And imagine your toes getting cold afterward
link |
and imagine the flow of blood coming to a halt
link |
and all of you clotting.
link |
And if you're really,
link |
you're going to be doing something with your physiology
link |
at that point that 99% of mammals out there only do
link |
if they're running frantically.
link |
And you're going to be turning on your synthetic
link |
stress response with thought, with emotions, with memory.
link |
And the measure of that is just how much the cortex
link |
and the limbic system sends projections down
link |
to all the autonomic regulators in the brain.
link |
You can think autonomic regulatory neurons into action
link |
in ways that only other animals can do with like extremes
link |
of environmental circumstances.
link |
And given that and the autonomic rule,
link |
I mean the other big challenge in understanding it
link |
is gigantic individual differences.
link |
And that's, you know,
link |
we talk about the optimal amount of stress
link |
that counts as stimulation.
link |
And in general, that stress that's not too severe
link |
and doesn't go on for too long
link |
and is overall in a benevolent setting.
link |
And under those conditions,
link |
we love being stressed by something unexpected
link |
and out of control and predictability
link |
like a really interesting plot turn
link |
in the movie you're watching.
link |
That's great, but you get the individual differences
link |
that somehow has to accommodate the fact that
link |
for some people, the perfect stimulatory amount of stress
link |
is like getting up early for an Audubon bird watching walk
link |
next Sunday morning.
link |
And for somebody else,
link |
it's signing up to be like a mercenary in Yemen.
link |
And tremendous individual differences
link |
that swamp any simple, you know, prescriptions.
link |
Yeah, the prefrontal cortex,
link |
this thinking machinery that we all harbor,
link |
it's such a double-edged sword.
link |
And what's remarkable to me is how the areas of the brain,
link |
like the hypothalamus and the amygdala,
link |
they're sort of like switches.
link |
I mean, there's context and there's gain control.
link |
You talked about the gain control by testosterone, et cetera,
link |
but they're really like switches.
link |
I mean, if you stimulate ventromedial hypothalamus,
link |
you get the right neurons,
link |
an animal will try and kill even an object
link |
that's sitting next to it.
link |
You tickle some other neurons,
link |
it'll try and mate with that same object.
link |
I mean, it's really wild.
link |
I think there are probably rules to prefrontal cortex also,
link |
but it sounds like the context, plural,
link |
from which prefrontal cortex can draw from
link |
is probably infinite.
link |
So that we could probably learn
link |
to perceive threat in anything,
link |
whether or not it's another group
link |
or whether or not it's science
link |
or whether or not it's somebody's version
link |
of the shape of the earth versus another.
link |
I mean, it's like you can plug in anything to this system
link |
and give it enough data.
link |
And I think it sounds like you could drive a fear response
link |
or a love response.
link |
Is that overstepping?
link |
Or a mixed, hardly ambivalent one
link |
that is changing by the millisecond
link |
and then like initially contradictory?
link |
No, that's absolutely the case.
link |
And the prefrontal cortex,
link |
I more than once have regretted
link |
having like wasted 30 years of my life
link |
studying the hippocampus
link |
when I should have been studying the prefrontal cortex
link |
because it's so much more interesting what it does.
link |
And it's all this contextual stuff.
link |
It's all the ways in which it's not okay
link |
to lie in this setting,
link |
but it's a great thing in another.
link |
It's not okay to kill unless you do it to them.
link |
And then you get a medal.
link |
It's not all of this social context
link |
and moral relativity and situational ethics stuff.
link |
That's the prefrontal cortex that's got to master that.
link |
And that winds up meaning that's the place
link |
in your brain more than anywhere
link |
where you say your perception of things
link |
can powerfully influence the reality
link |
of what's coming into you.
link |
I mean, great example of just harking back to testosterone.
link |
Okay, so exercise boosts up testosterone levels.
link |
Does exercise and success do it more than exercise
link |
and failure of literature back in the 80s or so
link |
looking at outcomes of marathons.
link |
Did testosterone rise more in the people who win
link |
Wrestling matches, things of that sort
link |
with a simple prediction.
link |
And the answer wound up being
link |
you didn't see a simple answer.
link |
Okay, you win the marathon.
link |
That's not necessarily an increase,
link |
a predictor of increased testosterone.
link |
What's that about?
link |
And then you find like the winner testosterone decreases
link |
and you find out the guy who came in 73rd
link |
is having a massive testosterone increase.
link |
Whoa, what's that about?
link |
What's that about is far more human subtlety.
link |
The guy who won the race has a decline in testosterone
link |
because he came in three minutes later
link |
than he really, really was expecting.
link |
And everybody now is going to be writing it up
link |
about how he's over the hill.
link |
And the guy who came in 73rd
link |
is having a boost of testosterone
link |
because he was assuming he'd be dead from a heart attack
link |
by the third mile and instead he managed to finish.
link |
It's this interpretive stuff going on in there
link |
and that's what prefrontal cortex is about.
link |
It raises this question of cognitive flexibility.
link |
Can we tell ourselves that something is good for us
link |
even if we're not enjoying it?
link |
Can we wriggle around these corners
link |
of choosing the exercise or doing the...
link |
I personally am not a big fan of long bouts of meditation
link |
but I've benefited tremendously
link |
from things like dedicated breathing
link |
and shorter rounds of meditation.
link |
Can I tell myself that it's good for me
link |
and wriggle around the corner
link |
and get my physiology working the way I want?
link |
Do we have cognitive flexibility?
link |
Can I be that third place runner and tell myself,
link |
well, at least I came in, I wanted to win so badly.
link |
That was my primary goal.
link |
But another goal was to beat my previous time
link |
and I did do that.
link |
And so, I mean, to what extent can we toggle
link |
this relationship between the prefrontal cortex
link |
and these other more primitive systems?
link |
And an enormous amount.
link |
For example, being low in a hierarchy
link |
is generally bad for health
link |
and like every mammal out there, including us.
link |
But we do something special,
link |
which is we can be part of multiple hierarchies
link |
And while you may be low ranking in one of them,
link |
you could be extremely high ranking in another.
link |
You're like have the crappiest job in your corporation,
link |
but you're the captain of the team softball,
link |
of the softball team this year for the company.
link |
And you better bet that's somebody
link |
who's gonna find all sorts of ways
link |
to decide that nine to five Monday to Friday
link |
is just stupid paying the bills.
link |
And what really matters is the prestige on the weekend.
link |
You're poor, but you're the deacon of your church here.
link |
And so we can play all sorts of psychological games
link |
And one of the most like consistent reliable ones
link |
that we do and need to use the frontal cortex like crazy
link |
is somebody does something rotten
link |
and you need to attribute it.
link |
And the answer is they did something rotten
link |
because they're rotten.
link |
Always have been, always will be
link |
this constitutional explanation.
link |
You do something rotten to somebody
link |
and how do you explain it afterward?
link |
A situational one.
link |
I was tired, I was stressed in this sort of setting.
link |
I misunderstood this.
link |
We're best at excusing ourselves from bad things
link |
because we have access to our inner lives.
link |
And we've got prefrontal cortexes that are great
link |
at coming up with a situational explanation
link |
rather than, hey, maybe you're just like
link |
a selfish rotten human and you need to change.
link |
And that's all prefrontal cortex.
link |
And we do that every time we don't let somebody,
link |
you know, merge in the lane in front of us
link |
even though you curse somebody
link |
who does the same thing to you and, you know, endlessly.
link |
Your statement about the fact
link |
that we can select multiple hierarchies to participate in
link |
to me seems like a particularly important one nowadays
link |
with social media being so prevalent.
link |
I know you're not particularly active on social media
link |
although you might be pleasantly or I don't know
link |
unpleasantly surprised to find out
link |
that there's a lot of positive discussion
link |
about you and your work.
link |
So you don't even need to be on there.
link |
We'll just continue to discuss your work.
link |
But what's interesting about social media
link |
I've found is that the context is very, very broad.
link |
I mean, one could argue that who one selects to follow
link |
and which news articles you're reading, et cetera,
link |
can create a kind of a funneling of information
link |
that itself can be dangerous.
link |
You know, more verification of crazy ideas
link |
or even just less exposure to new ideas.
link |
But there's also this idea
link |
that social media is an incredibly broad context.
link |
So as you scroll through a feed,
link |
it's no longer like being in your eighth grade classroom
link |
or your office or your faculty meeting.
link |
You are being exposed to thousands
link |
if not millions of contexts.
link |
This meal, that soccer game, this person's body,
link |
this person's intellect.
link |
YouTube is another example.
link |
It's a vast, vast landscape.
link |
So the context is completely mishmash.
link |
Whereas I'm assuming we evolved, I think we did evolve,
link |
under contexts that were much more constrained.
link |
We interacted with a limited number of individuals
link |
and a limited number of different domains.
link |
Seasons tend to constrain us all.
link |
And of course, then we got phones and televisions
link |
and this started to expand.
link |
But now more than ever, our brain,
link |
our prefrontal cortex and our sense of where we exist
link |
in these multiple hierarchies
link |
has essentially wicked out into infinity.
link |
How do you think this might be interacting
link |
with some of these more primitive systems
link |
and other aspects of our biology?
link |
Well, I think what you get is in some ways,
link |
the punchline of what's most human about humans,
link |
which is over and over, we use the exact same blueprint,
link |
the same hormones, the same kinases, the same receptors,
link |
the same everything.
link |
We're built out of the exact same stuff
link |
as all these other species out there.
link |
And then we go and use it in a completely novel way.
link |
And usually in terms of being able to abstract stuff
link |
over space and time in dramatic ways.
link |
So, okay, you're a low ranking baboon
link |
and you can feel badly because you just like killed a rabbit
link |
and you're about to eat and some higher ranking guy
link |
boots you off and takes it away from you.
link |
And you feel crummy and it's stressful and you're unhappy.
link |
We are doing the exact same things with like our brain
link |
and bodies when we're losing a sense of self-esteem,
link |
but we can do it by watching a movie character on the screen
link |
and feeling inadequate compared to like how wonderful
link |
or attractive they are.
link |
We can do it by somebody driving past us in an expensive car
link |
and we don't even see their face.
link |
And you can feel belittled by your own socioeconomic status.
link |
You can watch like the lifestyles of the rich and famous
link |
or read about what Bezos is up to.
link |
And for some reason decide your life is less fulfilling
link |
because you didn't fly into space for 11 minutes.
link |
And so you can feel miserable about yourself
link |
in ways that no other organism can simply
link |
because we can have our meaningful social networks include
link |
like the party you're reading about on Facebook
link |
that you weren't invited to
link |
because it's taking place in Singapore
link |
and you don't know any of those people.
link |
But nonetheless, somehow that could be a means
link |
for you to feel less content
link |
with who you've turned out to be.
link |
Do you take steps in your own life
link |
to actively restrict the context in which you think
link |
and live and contemplate, you know,
link |
in order to enhance your creative life,
link |
your intellectual life,
link |
are those steps that you actively take?
link |
Well, I very actively don't know how to make use
link |
of anything with social media.
link |
So I guess that counts as my having thus actively chosen
link |
So that's the case, certainly for the last year and a half,
link |
like lots of people, I've gone through stretches
link |
where I've managed to sort of enforce a moratorium
link |
on looking at the news and that was wonderfully freeing.
link |
I think in the larger sense though, you know,
link |
in addition to me being a neurobiologist,
link |
I sort of spent decades spending part of each year
link |
studying wild baboons out in a national park in East Africa.
link |
And I'd spend three months a year without electricity,
link |
without phone calls, with, you know, going 12 hours a day
link |
without saying a word to somebody.
link |
And when I finally would, it would be somebody,
link |
a nomadic pastoralist guy in a different language.
link |
Yeah, I did 90% of my like insightful thinking
link |
about anything in the laboratory
link |
during those three months each year
link |
and not one in the lab and not one inundated with stuff.
link |
Well, I think there's sort of a shifting trend
link |
towards trying to create a narrowing of context
link |
that people, and I like what I see.
link |
I have a niece, she's 14 years old,
link |
and she and her friends are very good
link |
at putting their phones away.
link |
They say, we're not going to have our phones
link |
for this interaction, especially after,
link |
and I realize we're still somewhat in this,
link |
it's unclear where it's headed,
link |
but at 2020 was so restrictive
link |
and she was so separated from her friends.
link |
Now it's let's really focus on being together
link |
and not bring in all these other elements from our phones.
link |
And that brings me great hope for that generation.
link |
Maybe they will, you know, or who knows,
link |
maybe they'll run off and study baboons.
link |
We need more field researchers.
link |
So along the lines of choice,
link |
I'd like to shift gears slightly and talk about free will,
link |
about our ability to make choices at all.
link |
Well, my personal way out
link |
and left field inflammatory stance is,
link |
I don't think we have a shred of free will.
link |
Despite, you know, 95% of philosophers
link |
and I think probably the majority of neuroscientists
link |
saying that we have free will
link |
in at least some circumstances,
link |
I don't think there's any at all.
link |
And the reason for this is you do something,
link |
you behave, you make a choice, whatever.
link |
And to understand why you did that,
link |
where did that intention come from?
link |
Part of it was due to like the sensory environment
link |
you were in in the previous minute.
link |
Some of it is from the hormone levels
link |
in your bloodstream that morning.
link |
Some of it is from whether you had a wonderful
link |
or stressful last three months
link |
and what sort of neuroplasticity happened.
link |
Part of it is what hormone levels
link |
you were exposed to as a fetus.
link |
Part of it is what culture your ancestors came up with
link |
and thus how you were parented when you were a kid.
link |
All of those are in there
link |
and you can't understand where behavior is coming from
link |
without incorporating all of those.
link |
And at that point, not only are there
link |
all of these relevant factors,
link |
but they're ultimately all one factor.
link |
If you're talking about what evolution
link |
has to do with your behavior,
link |
by definition, you're also talking about genetics.
link |
If you're talking about what your genes
link |
have to do with behavior,
link |
by definition, you're talking about
link |
how your brain was constructed
link |
or what proteins are coded for.
link |
If you're talking about like your mood disorder now,
link |
you're talking about the sense of efficacy
link |
you were getting as a five-year-old.
link |
They're all intertwined.
link |
And when you look at all those influences,
link |
basically like the challenge is show me a neuron
link |
that just caused that behavior
link |
or show me a network of neurons
link |
that just caused that behavior
link |
and show me that nothing about what they just did
link |
was influenced by anything from the sensory environment
link |
one second ago to the evolution of your species.
link |
And there's no space in there
link |
to fit in a free will concept
link |
that winds up being in your brain, but not of your brain.
link |
There's simply no wiggle room for it there.
link |
So I can appreciate that our behaviors and our choices
link |
are the consequence of a long line of dominoes
link |
that fell prior to that behavior.
link |
But is it possible that I can intervene
link |
in the domino effect, so to speak?
link |
In other words, can my recognition of the fact
link |
that genes have heritability,
link |
there's an epigenome that there's a hormonal context,
link |
there's a historical context,
link |
can the knowledge of that give me some small,
link |
small shard of free will?
link |
Meaning does it allow me to say, ah, okay,
link |
I accept that my choices are somewhat predetermined
link |
and yet knowing that gives me
link |
some additional layer of control.
link |
Is there any philosophical or biological universe
link |
in which that works?
link |
So all of that can produce
link |
the wonderfully positive belief that change can happen.
link |
Even dramatic change, even in the worst of circumstances,
link |
most unlikely people, and change can happen.
link |
Things can change.
link |
Don't be fatalistic, don't decide
link |
because we're mechanistic biological machines
link |
that nothing can ever, change can happen.
link |
But where people go off the rails
link |
is translating that into, we can change ourselves.
link |
We don't, we can't, because there's no free will.
link |
However, we can be changed by circumstance.
link |
And the point of it is,
link |
like you look at an aplasia, a sea slug
link |
that has learned to retract its gill in response
link |
to a shock on its tail, you can do like conditioning,
link |
Pavlovian conditioning on it, and it has learned
link |
its behavior has been changed by its environment.
link |
And you hear news about something
link |
like horrifically depressing going on
link |
and, you know, refugees in wherever.
link |
And as a result, you feel a little bit more helpless
link |
and a less of a sense of efficacy in the world.
link |
And both of your behaviors have been changed.
link |
Okay, okay, yeah, I guess that's good.
link |
But the remarkable thing is it's the exact same neurobiology.
link |
The signal transduction pathways that were happening
link |
in that sea snail incorporate the exact same kinases
link |
and proteases and phosphatases that we do
link |
when you're having mammalian fear conditioning
link |
or when you're learning, it's conserved,
link |
it's the exact same thing.
link |
It's simply playing out
link |
in obviously a much, much fancier domain.
link |
And because you have learned that change is possible
link |
despite understanding mechanistically
link |
that we can't change ourselves volitionally,
link |
but because you understand change is possible,
link |
you have just changed the ability of your brain
link |
to respond to optimistic stimuli.
link |
And you have changed the ability of your brain
link |
to now send you in the direction
link |
of being exposed to more information
link |
that will seem cheerful rather than depressing.
link |
Oh my God, that's amazing what Nelson Mandela
link |
and Martin Luther King and all these folks did.
link |
Wow, under the most adverse of circumstances,
link |
they were able to do, maybe I can also.
link |
Maybe I can go read more about people like them
link |
to get even more data points of change to neurochemistry
link |
so that your responses are different now.
link |
And you're tilted a little bit more in that direction
link |
of feeling like you can make a difference
link |
instead of it's all damn hopeless.
link |
So enormous change can happen,
link |
but the last thing that could come out of a view
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of we are nothing more or less than the sum of our biology
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and its interactions with environment
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is to throw up your hands and say,
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and thus it's no use trying to change anything.
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So we can acknowledge that change
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is extremely hard to impossible,
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that circumstances can change,
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and yet that striving to be better human beings
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is still a worthwhile endeavor.
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Do I have that correct?
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Absolutely, because simply the knowledge
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either from experience or making it to the end
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of the right neurobiology class has taught you
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that change can happen within a framework
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of a mechanistic neurobiology.
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You were now more open to being made optimistic
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by the good news in the world around you.
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You were more likely to be inspired by this or that.
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You were more resistant to getting discouraged by bad news.
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Simply because you now understand it's possible.
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Yeah, somebody who spent much of his career
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working on the hippocampus,
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I have to assume that you are a believer in neuroplasticity,
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that neural circuits can change in response to experience
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and that some of the same so-called top-down mechanisms
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of prefrontal cortex that we were talking about before
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can play a role there,
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that the decision to try and change
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and the pursuit of knowledge and the pursuit of experience
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can shape our circuitry
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and therefore make us different machines, so to speak.
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Yeah, and not only can say prenatal hormone exposure
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change the way your brain is being constructed,
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but learning that prenatal hormone exposure
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can change the construction of your brain
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will change your brain right now
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and how you think about where your intentions came from.
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Wow, maybe that had something to do with it.
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The knowledge of the knowledge
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is an effector in and of itself.
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That's such an important and powerful statement to hear.
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I think that many people think that if a tool,
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it doesn't involve a pill or a protocol,
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that it's useless.
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And certainly there are pills and protocols
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that are very useful in a variety of contexts
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for a variety of things.
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But the idea that knowledge itself,
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or as you put it, knowledge of knowledge is itself a tool,
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I think is a very important concept
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for people to embed in their minds.
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And listen, I'm so grateful for this discussion
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and for you raising these topics.
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I think that many people know your work
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on testosterone, on stress,
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and we've covered some of that today.
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The work on free will and this idea that we are hopeless
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or that we are in total control,
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I think I'm realizing and listening to you
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that neither is true and that the solution resides
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in understanding more about free will and lack of it
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and also neuroplasticity.
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You're working on a book about free will.
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Are you willing to tell us a little bit about that book
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and where you are in that process
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and what we can look forward to?
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Yeah, it's going really slow.
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Title is Determined, A Science of Life Without Free Will.
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And essentially the first half of the book
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is trying to convince a reader,
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okay, if not that there's no free will whatsoever,
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but at least there's a lot less than is normally assumed.
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And I'm going through all the standard arguments
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for free will and why that doesn't make sense
link |
with 21st century science.
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And that has led to reading a lot
link |
of very frustrating philosophers
link |
who basically are willing to admit
link |
that stuff is made out of like atoms and molecules
link |
and like there's a physical reality to the world.
link |
They're not just relying on magic,
link |
but that they believe in free will for magical reasons
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and where it doesn't make sense.
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Okay, so the first half of the book is
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to hopefully convince people
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that there's much less free will than they used to think.
link |
And then the second half is this gigantic juncture
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built around the fact that I haven't thought
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there's any free will since I was like an adolescent.
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And despite thinking that way,
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I still have absolutely no idea
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how you're supposed to function with that belief.
link |
How are you supposed to like go about everyday life
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if anything you feel entitled to isn't true,
link |
if any angers and hatreds you feel aren't justified,
link |
if there's no such thing as appropriate,
link |
blame or punishment or praise or reward,
link |
and none of it makes any sense.
link |
And somebody like even compliments you on your haircut
link |
and you've been conditioned to like say,
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oh, thanks as if you had something to do.
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How are we supposed to function with that?
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And so the second half is wrestling with that.
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And what the punchline there is,
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is it's gonna be incredibly hard.
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And if you think it's gonna be hard
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to subtract a notion of free will
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out of making sense of like serial murderers,
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it's gonna be a thousand times harder
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of making sense of when somebody says good job to you.
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And because it's the exact same unreality
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of sort of our interpretations,
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it's gonna be incredibly hard.
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But nonetheless, when you look at the history
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of how we have subtracted the notion of agency
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out of all sorts of realms of blame,
link |
starting with thinking that witches
link |
caused hailstorms 500 years ago
link |
to the notion that psychodynamically screwed up mothers
link |
caused schizophrenia, we've done it.
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We've done it endless number of times.
link |
We've been able to subtract out a sense of volition
link |
in understanding how the world works around us.
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And we don't have murderers running amok on the street
link |
and society hasn't collapsed into a puddle.
link |
And in fact, it's a more humane society.
link |
So the good news is it's possible
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because we've done it repeatedly in the past,
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but it's gonna be hard as hell.
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And it's hard as hell to try to write about that coherently
link |
on discovery and so it's going slowly.
link |
Well, I speak for many, many people
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when I say that we're really excited
link |
for the book when it's done and we will patiently wait,
link |
but with great excitement for the book, Determined,
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you said is the title, correct?
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Yeah, Determined for the Science of Life Without Free Will.
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Seems like you can't publish your book these days
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without a subtitle, so that's it.
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Well, very excited to read the book.
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Very grateful to you for this conversation today.
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Every time you speak, I learn.
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And for me, it's really been a pleasure
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and a delight to interact with you today
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and over the previous years, I should say as colleagues.
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And thank you again, Robert, for everything that you do
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and all the hard, hard work and thinking
link |
that you put into your work,
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because it's clear that you put a lot of hard work
link |
and thinking and we all benefit as a consequence.
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Thanks and thanks for having me.
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Thank you for joining me for my conversation
link |
with Dr. Robert Sapolsky.
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If you're enjoying this podcast and learning from it,
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please subscribe to our YouTube channel.
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In addition, you can leave us comments and suggestions
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Please also subscribe on Apple and on Spotify.
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And on Apple, you have the opportunity to leave us
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In addition, please check out the sponsors
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that we mentioned at the beginning of this podcast.
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That's a terrific way to support us.
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And for those of you that are interested
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in supporting research on stress, on sleep,
link |
and how to better access sleep and combat stress,
link |
you can do that by supporting the research being done
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on those topics in my laboratory.
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You can go to Hubermanlab.stanford.edu
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and there you'll see a tab entitled support research
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in the Huberman Lab.
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So that's for work at the Huberman Lab at Stanford,
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not the Huberman Lab podcast.
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And there's a make a donation tab
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on Instagram and on Twitter.
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On both those channels, I post information about science
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and science-related tools anywhere from one to five minutes.
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Some of that information overlaps with the podcast,
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but a lot of it is unique and different
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from the information on this podcast.
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And last but not least,
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thank you for your interest in science.
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And I'll see you in the next one.