Huberman Lab - How Hormones Shape Sexual Orientation & Behavior | Dr. Marc Breedlove

Episode Date: March 30, 2026

Dr. Marc Breedlove, PhD, is a professor of neuroscience at Michigan State University and an expert on how hormones shape brain development and sexual orientation. We discuss how prenatal testosterone ...impacts whether someone is romantically attracted to men or women later in life, and what correlates of sexual orientation — such as finger-length ratios — tell us about the role of hormones in brain and psychological development. We also discuss why the number of older brothers a male has biases sexual orientation. Throughout, we explain how nature and nurture interact to shape male-female differences, behavior, and romantic partner choice. Thank you to our sponsors AG1: https://drinkag1.com/huberman David: https://davidprotein.com/huberman Rorra: https://rorra.com/huberman Function: https://functionhealth.com/huberman Timestamps (00:00:00) Marc Breedlove (00:03:24) Hormones & Sexual Orientation (00:07:37) Prenatal Testosterone, Finger Ratio, Men & Women Differences (00:14:08) Sponsors: David & Rorra (00:16:46) Finger Ratios, Prenatal Testosterone, Gay & Straight Men/Women (00:23:57) Mice & Sex Differences, Androgens (00:26:54) Brain Differences & Sexual Orientation (00:33:52) Group vs Individual Differences, Height Analogy; Bisexuality (00:36:57) Brain Development, Hormones & Behavior; Brain Plasticity (00:42:52) Sponsor: AG1 (00:44:16) Sexual Behavior, Libido (00:51:37) Gay Rams, Brain Differences (00:58:00) Aversion Pathway, Men vs Women, Same-Sex Partner (01:06:58) Congenital Adrenal Hyperplasia (CAH), Intersex Phenotypes (01:13:55) Androgen Insensitivity Syndrome (AIS) (01:18:14) Sponsor: Function (01:19:25) Gay Men & Older Brothers, Maternal Immunization Hypothesis (01:32:55) CAH Carriers, Advantage, Stress Tolerance (01:35:41) Birds & Sexual Differentiation, Gynandromorphs (01:41:32) Anabolic Steroids, Hypersexuality; Adult Brain Plasticity (01:45:31) Age & Testosterone Decline; Sexual Orientation & Activities (01:53:14) Marc's Academic Journey, Ozarks, Luck (02:02:35) Exploration; Kids & Sex Differences (02:08:47) Zero-Cost Support, YouTube, Spotify & Apple Follow, Reviews & Feedback, Sponsors, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures Learn more about your ad choices. Visit megaphone.fm/adchoices

Transcript
Discussion (0)
Starting point is 00:00:00 The larger the number of older brothers that a male has, the higher the probability that he is gay. It's been seen over and over. I mean, it's really one of the rock-solid findings in human sexuality. So the way to emphasize the difference is if a baby boy is born today, if he has no older brothers, his odds of being gay when he grows up is about 2%, right? Pretty low. but if he had one older brother, his odds go up by a third. Okay, 2.6.
Starting point is 00:00:34 And if he has two older brothers, they go up a third again. All right, now we're at 3.5. It turns out you've got to have like a dozen older brothers just to have a 50-50 chance. Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Mark Breedlove. Dr. Mark Breedlove is a professor of neuroscience at Michigan State University,
Starting point is 00:01:05 and he is an expert in how hormones shape the developing brain, in particular how they influence sexual orientation. As you'll learn today, the amount of testosterone that a fetus is exposed to while in the mother has a profound impact not only on the ratio of finger lengths, yes, you heard that right, but it also plays a meaningful role in sexual orientation, and in fact, there's a correlation
Starting point is 00:01:28 there between finger length ratios and sexual orientation. Now, as wild as that may seem, that result has now been confirmed many times over in humans and in animals. And today, you'll understand why. You'll also learn that every time a woman is pregnant with a male, there's a biological trace of that, which biases the likelihood that her next male offspring will be either heterosexual or homosexual. Now, I know this sounds really out there, but these are extremely solid biological findings for which the mechanisms are now on understood for both animals and humans. It turns out that the hormones we are exposed to
Starting point is 00:02:02 while we are in the womb shape not only the preference for whether somebody is attracted to males or females, but also an aversion to the opposite. Meaning there appears to be the formation of circuits for being attracted to one sex and not attracted to the other. Today you'll also learn how hormones impact the amount of rough and tumble or social play that kids engage in, the interplay between nature and nurture
Starting point is 00:02:23 in shaping male versus female differences and sexual orientation. Dr. Breedlove is one of the longstanding pioneers in this field of how hormone-shaped brain development and psychology. We approach these questions through the lens of biology and statistics. So today's is not a political discussion.
Starting point is 00:02:41 Instead, it's a discussion about what is known and what is still not known about this profound aspect of our species. Oh, and we also talk about gay Rams. Yes, that's a real thing, and it has important implications for everything we've mentioned thus far. By the end of today's episode,
Starting point is 00:02:56 you'll surely think differently about the relationship between hormones and brain development, nature and nurture, and romantic partner choice. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Mark Breedlove. Dr. Mark Breedlove. Welcome.
Starting point is 00:03:25 Thank you. I'm delighted to be here. Very exciting. Been 25 years since we stood in the same physical space. I know. How can that be possible when I feel like, you know, just saw you a few days ago, but then... Well, you look great. You look the same, so we can talk a longevity protocols at the end, but... I'm trying to have a blonde look in my hair, apparently, so... Well, I've wanted to have you on this podcast since I launched it because you work on one of the most interesting things in the world, which is how and why people... will become who they are and how hormones play a role there, how genes play a role there. If you're willing, I'd like to jump from the high dive to the deep end first, right?
Starting point is 00:04:06 All right. Let's talk about this finger length ratios, sexual orientation study that you published, and somehow I landed on that paper. That's not why I want to talk about it. I want to talk about because it's an incredibly interesting set of findings. Other people have done the same-ish experiments, and there's a whole context there about, how hormones influence sexual orientation independent of behavior. We need to step back a little bit for the context.
Starting point is 00:04:34 One thing that your listeners might not know is, you know, in the year 2000, there was still a lot of people who regarded same-sex orientation as a choice, a lifestyle choice. That was the political combination of words that meant you could disapprove of people because they were attracted to the same sex. course, I'm at Berkeley. I didn't have any truck with such notions at all. And I've always been convinced that sexual orientation is not a choice. And there's exercise they do in class where I ask, so I'm going to put you to it. So remember the first time you had a crush, right? It might have
Starting point is 00:05:13 been someone on TV, it might have been someone in a playground, et cetera. So think about that. And I want you to tell me about how old you were at the time in a moment. My guess is it was before puberty. Yeah, I was six. And I hit puberty somewhere starting around 14. So it had nothing to do with puberty, right? It was this thing that happened. And I'll share my experience. So I'm about six or seven. I couldn't have been more than seven. And Marilyn Monroe is on TV. I'm dating myself. And there's a close up, you know, with that face and the, and the mole, et cetera. And afterwards, I'm just so agitated. I don't, you know, I don't, and I know nothing about. sex. I remember I had a hard time going to sleep, so it was like something about this was really
Starting point is 00:05:58 agitating me, and I didn't choose to have that reaction. And my guess is that whatever sex you had your first crush on, that's the one you're going to be attracted to the rest of your life. Yeah, it's been constant. Yeah. So this idea that it was a choice that always just seems so absurd to me. On the other hand, even though I've been doing animal research with giving hormones early in life and seeing what it did the nervous system, et cetera. And every time I wrote an NIH grant, I said, well, you know, the effect of early hormones may be important for human behavior, but to tell you the truth, I never actually believed that, right? It was just, I just wanted to justify it because it seemed to me that we are so sensitive
Starting point is 00:06:43 to social influences. And we have this long stretch of time where, you know, our brains are still growing at a fetal rate of growth until like nine or ten years of age, and we're taking in so much information. And think of what a heterosexual world is, right? I'm about all those Disney movies with Prince Charming and, et cetera. And so it always seemed to me that social learning would be more than enough to explain why 95% of people are straight. But that doesn't mean that was a choice, and it doesn't mean that they would even be aware of what the social influence was. So, So my example is, I speak English. It's, you know, I'm hopelessly monolingual, only language to speak.
Starting point is 00:07:27 Well, I don't remember learning English, and I certainly didn't choose to learn English, but I'm sure that it's English because of social influences, right? So that was where I stood on the question of sexual orientation until 1998, 1999. When this fellow at University of Texas, Dennis McFadden, came out with a paper where it really made me think that prenatal testosterone might have an effect after all, despite my expectations. And this was looking at auto-acoustic emissions. Do you want to talk about those?
Starting point is 00:08:04 These are people's ears making noise. Yeah. I mean, right now in this studio, if I shut up for a moment, your ears will continue to make little popping sounds that you're not aware of, because having grown up with it, the brain stopped you from, perceiving those long ago. Well, but if Dennis puts you in a soundproof room and puts a very sensitive microphone in your ear, he'll hear these pops. And I won't get into the acoustics of why that's a good thing, right? It helps you to focus on the sounds you want to hear. But what Dennis
Starting point is 00:08:40 knew is there's a sex difference in how many of these auto-acoustic emissions are being made. girls make more and it's present at birth. So Dennis comes out with a strange study. I mean, who would do such a thing? Where he proposes, well, since the sex difference is present at birth, it might reflect prenatal testosterone. And so he measured the auto-acoustic emissions in straight men and gay men and straight women and lesbians.
Starting point is 00:09:09 And he reports that compared to straight women, the lesbians have fewer of these auto-acoustic emissions than straight women. It's like, well, what? How would that happen? I couldn't think of any way to explain that, except that, well, the lesbian might have been exposed to more prenatal testosterone than straight women before birth.
Starting point is 00:09:36 And I don't know how to explain that except to say, well, maybe prenatal testosterone, maybe if you're exposed to that before birth, you're more likely to be attracted to women when you grow up, which, oh, Well, that might explain why 95% of men are attracted to women, right? Because they're all exposed to prenatal testosterone. So this oddball study really gets me to thinking that maybe there's, you know, something to that.
Starting point is 00:09:58 But I'll forget it. You know, I'm still working with my rats and paramiscus and Siberian hamsters and stuff. I'm happily doing that. And then, and I remember it so well. And I, in 1999, I'm in my office at Berkeley, and I read this paper that says there's a sex difference in the ratio of fingers that's present in nine-year-old children. What? I've studied sex differences my whole adult life.
Starting point is 00:10:27 How do I not know about this? And it turns out that if you measure the length of the second digit, the pointer finger, the pointer finger. For those just listening, yeah. Right. And the length of the ring finger. And you can do a simple ratio. Divide the length of the second digit by the fourth digit,
Starting point is 00:10:44 so-called 2D-4. 40 ratio. And a guy named John Manning was reporting that there's a sex difference there, that that ratio tends to be smaller in men than in women, and that it's present in children. It's like, well, wait a minute, a sex difference in the body that's present before puberty, I know enough about sexual differentiation in the body. It's almost certainly due to prenatal testosterone. Forgive me for interrupting you, but people are probably looking at their hands right now. And I just want to point out that these are averages. Yes.
Starting point is 00:11:18 But it's, I think the 2D-4D thing for people that aren't familiar, even though you explained it quite clearly can be a little confusing. Basically, in men, the finger lengths are more different than they are in women. And there are some differences in that statement, according to sexual orientation that we'll get into. But when you say, in other words, the typical heterosexual male pattern is that the pointer finger, right, is shorter than the ring finger.
Starting point is 00:11:45 Right. Right. Whereas in women, they tend to be more similar. Again, these are averages. And not to give it away, but this is because people are looking at their fingers right now. Let me just say, don't panic. Yeah, right. We're going to walk you through this. You're going to be fine.
Starting point is 00:12:01 And the difference between men and women is more pronounced on the right hand, as I recall. That's true, too. Did I earn my authorship on the paper? Well, that and the fact that you persuaded so many people to answer our weird questions, let us see rocks their hands. Okay, so please continue. But I know that the moment that came out, you know, hopefully there were no car accidents that people were driving.
Starting point is 00:12:21 But these are averages, but that's the pattern that was observed. That's the pattern. Well, I'd never worked with humans before, but I'm sitting in the Bay Area. We have loads of gay people around them. So it's like, well, let's, I guess we could try to do this. this. And so we started going out to street fairs. You were with us going out to street fairs and giving people, asking people questions, asking them to fill out a questionnaire anonymously. And I remember it was one of the organizers of one of the street fair, but I said, well,
Starting point is 00:12:59 what should we do as an incentive to get people? And they said, well, offer them scratcher tickets. Lottery tickets. So we ask people, will you please answer these very personal questions about about who you have sex with, who you want to have sex with, et cetera, and tell us everything about yourself anonymously, and we'll give you a $1 lottery scratcher ticket. And people will do anything for a $1 lottery scratcher ticket. I mean, it was just a bit, which is weird because you do the math, the word's like 27 cents, right?
Starting point is 00:13:30 But people want them. And, oh, and by the way, can we Xerox your hands? And the last two questions we asked about handedness, but it was really just to keep them from panicking. So, you know, by the way, it was the least expensive experiment I'd ever done in my life because really, you know, compared to any experiment with rat where step one, buy a rat for 20 bucks, right? So it's, so it was an odd experience going in the 7-Eleven that morning and saying, please, I'd like 750 one-dollar scratch for tickets.
Starting point is 00:14:08 I'd like to take a quick break to acknowledge one of our sponsors, David. David makes protein bars unlike any other. Their newest bar, the bronze bar, has 20 grams of protein, only 150 calories, and zero grams of sugar. I have to say, these are the best tasting protein bars I've ever had, and I've tried a lot of protein bars over the years. These new David bars have a marshmallow base, and they're covered in chocolate coating, and they're absolutely incredible.
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Starting point is 00:15:02 Again, they're amazing. But again, they have no sugar and they have 20 grams of protein with just 150 calories. If you'd like to try David, you can go to Davidprotein.com slash Huberman. Right now, David is offering a deal where if you buy four cartons, you get the fifth carton for free. You can also find David on Amazon or in stores such as Target, Walmart, and Kroger. Again, to get the fifth carton for free, go to Davidprotein.com slash Huberman. Today's episode is also brought to us by Rora. Rora makes what I believe are the best water filters on the market. It's an unfortunate reality, but tap water often contains contaminants that negatively impact our health.
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Starting point is 00:16:40 and get an exclusive discount. Again, that's Rora, rora, r o rara.com slash Huberman. Well, as long as we're getting into the context, it's interesting because you said there are a lot of gay people in the Bay Area, but it was very clear, as I recall, when doing the study, that if we wanted to get a large sample population of gay men, we would need to go to the Castro district in San Francisco.
Starting point is 00:17:04 Yeah, as we did. And if we needed to get a large cohort of gay women, we need to go to the Solano Street Fair in Berkeley. And in Oakland. So there was a brand new Oakland gay festival that got started. And, yeah, Oakland is a wonderful place to find lesbians. So what are the charms of the place? I thought the whole idea was kind of crazy, actually.
Starting point is 00:17:26 I mean, I didn't think we'd come up with anything. And I insisted on measuring all the digits myself, right, which I did. did twice. Boring as hell. I recall when we were on what was like third floor of Tolman Hall and you came running in. I was talking to my advisor, our good friend Erf Zucker, one of the pioneers of circadian biology, discovered the superchaismatic nucleus with Bob Moore and others. And you came running in with a ruler and you said, give me your hands. And you grab my hands and you measured them and you go, well, that's weird because it's like different on one hand than the other. And And then you'd go, okay, and you took the notes and he measured his hands, and he left.
Starting point is 00:18:05 And I thought, what in the world is he doing? It turns out that was the early origins of the study. Yeah. Yeah. No, no. And anyway, so I measure these hands and I'm doing the math at the end of the day. And lo and behold, I mean, I don't see any difference in the digit ratios of gay and straight men, right? Okay.
Starting point is 00:18:26 Between gay and straight men. Yeah, yeah, I didn't see any difference there. Which itself is interesting. Absolutely. Because it implies, more or less. equivalent amounts of prenatal testosterone exposure. Which I think is the case. Yes.
Starting point is 00:18:37 And right now, just forgive me, but some people might say, well, that's not surprising. But in the 80s and 90s, the Hollywood stereotype of gay men was that they were all very effeminate. Yep. Since then, there's been an evolution. In fact, I haven't seen it, but many people I know are very excited about this recent show about these two gay hockey players. Yes, yeah. So the whole context is these guys that are very masculine, but.
Starting point is 00:19:02 but are gay, right? So for people hearing this that are younger than 40, they're going to think, well, duh. But for people that grew up in my generation or your generation, it was a bit of a shocker to a lot of people because, depending on their level of exposure to the gay community, they may or may not have realized that not all gay men are effeminate. Exactly. And, and, you know, that idea that gay men might have been under-androgenized, There was always a part of it that always seemed strange to me. So the big sex differences in human behavior are not in, you know, math skills and verbal skills. Those are tiny, right?
Starting point is 00:19:40 The really big sex differences in human behavior are in sexual attitudes. And the biggest sex difference is one sex is much more interested in multiple partners and younger partners than the other, right? Everyone knows which sex that is. one sex is much more interested in casual sex than the other. Everyone knows one. One sex is much more interested in visual pornography than the other sex. Those are huge sex differences compared to any, you know, cognitive things. And in all those ways, gay men are totally masculine.
Starting point is 00:20:15 So how would that work that, you know, they were under-angi-inized, and yet they have all these sex difference in sexual attitude? I think the difference between gay and straight men is, in how much prenatal testosterone they got, I think it's in how their brains responded to the testosterone that they got. We can talk about that some more later. But back to the digit ratios, the lesbians had more masculine digit ratios than the straight women, on average. And as you say, that's been replicated by many different labs. Dave puts it at Penn State and Ashland Swift, Galant and I recently published a, like, the third meta-analysis, and it's clear so many people have seen it.
Starting point is 00:21:00 It's there. And as with Dennis's auto-acoustic emissions, I don't know how to explain that. Why would lesbians have a more masculine digit ratio than straight women unless, on average, they were exposed to more prenatal testosterone than straight women? And why would that matter, unless being exposed to prenatal testosterone makes you more. inclined to be attracted to women when you grow up. And what's really weird about it, think about the time lag, your first crush, this sudden, this mysterious, for me, it was like a visitation, right? It's like, where'd this come from?
Starting point is 00:21:39 That happened six years after you were out of the womb, right? And so it's really strange to think that something that happened to you before you were born would have an influence on who you're going to be attracted to six, ten years. years later when you have your first crush. So it was, and I can tell you that when we published that in 2000, it did cause quite an uproar. I heard from a lot of strangers that I'd never heard from before. And it was pretty interesting. Of course, there were several people wrote who had told me that they were gay, and they were very positive, very supportive. But I got lots of emails from people saying, I know you're lying.
Starting point is 00:22:26 You know, you're making this up to justify your gay lifestyle. You know, it's like, well, okay, except I don't happen to be gay. I mean, we had a nice mix of orientations on the research team, but people were having a hard time with it. And to assure your listeners about if they were looking at their hands, if they're a woman and they looked at the hands and they see that the index finger is quite a bit shorter than the ring finger, and they're thinking, I thought I was straight. etc. So here's a joke that I tell, which is, if you want, I'm going to teach you right now.
Starting point is 00:23:00 You gather a big sample of people, and I'm going to teach you how to look at their hands, look at the right hand, and guess their sexual orientation, and you're going to be right 95% of the time. Okay, you want to learn how? So look at the right hand, pay really careful attention to whether the index finger is shorter than the ring finger, and no matter what, you see guess straight. and you will be right 95% of the time if it was a random sample of people. So the important thing to get across is that while these average differences across group
Starting point is 00:23:33 are theoretically important because they do indeed indicate that lesbians are more likely to have been exposed to slightly more testosterone before birth, that doesn't mean you can predict how much testosterone one person was exposed to from their tituration because other things influence.
Starting point is 00:23:51 did geracious. Fascinating study. I got made fun of quite a lot, but, you know, I thought it was a blast. I mean, some of the more outrageous things that people have asked me about the study over the years were, and by the way, they all came from men, were if I cut off my index finger, you know, will that raise my testosterone? Someone actually asked that. No, it's not reverse causality. I would have said, well, let's try it and see. Again, now, most of the most of the I realize there are differences across the country in the world on this stance, but I think most people would say, yeah, like, okay, there's a biological variable associated with sexual orientation. The fact that it's linked to prenatal testosterone is very interesting. And the question that then comes up is, is there anything about behaviors associated with gay or straight men, gay or straight women, that change hormone levels, independent of of all this, right? Because put differently, I think for a number of years, people were interested in whether or not gay men, as you pointed out, would have higher or lower levels of testosterone.
Starting point is 00:25:00 The hypothesis was lower based on the effeminate stereotype. Turned out probably the opposite outcome. If anything, right. Yeah. Anyone that went to gyms in the 1980s and 90s would also realize that the low androgen argument was wrong, although steroids become a problem in gyms too, but, you know, it gets confounded. But am I correct in remembering that this effect is also present in frogs or mice? The sex difference is present in mice. That's D2D4 ratio difference. Yes. I mean... I find that amazing. Well, I did too. So, so Wendy Brown and I did that first. And, you know, I'd work with mice and rats all my life. But, you know, I'd never noticed that that this is their, that the first digit is the shortest. And, you know, I'd work. And
Starting point is 00:25:50 and that the third digit is the longest and that sometimes the second digit is longer. I mean, you know, it's like, I mean, evolution's real, right? It happened. And so, yeah, there's a sex difference there, and a group looked at mice and did lots of genetic manipulations, and it turns out that if you make the angrient receptor dysfunctional, the sex difference goes away. And they showed that in mice at least, there's more and receptor in the growing bones, of the fourth digit than the second digit. And then they showed that that's why the fourth digit
Starting point is 00:26:26 grows a little bit more than the second digit. Beautiful. And I should have said this earlier. Androgens are things like testosterone, DHT, other endrogens. Men and women both have them. Other animals have them. Incredible. So let's talk about effects of testosterone
Starting point is 00:26:45 when we're in the womb. Obviously, it's having an organizing effect on the body plan, this D4-D2 ratio. What about in the brain? What is known about brain differences between men and women that identify as straight or gay? Well, in terms of prenatally, we don't know, but the very famous study from Simon LeVay, who was already a highly respected neuroscientist, lots of wonderful papers in development of the visual system, Simon LeVay got everyone's attention well before we did when he looked at a brain region in the hypothalamus,
Starting point is 00:27:26 a specific region called the pre-optic area, or P-O-A, and he looked there and compared the size of the P-O-A in the brains of gay men versus straight men. And he looked in the pre-optic area because in rats, there's a very prominent sexual difference or sex dimorphism in a nucleus in the rat brain in the pre-optic. optic area and the nucleus got named the sexually diomorphic nucleus of the preoptic area, the SDNPAA. And Simon knew there was a huge sex difference there in rats. And so he looked at the brains of gay and straight men and found a nucleus there that may or may
Starting point is 00:28:06 not be the same as the SDNPOA, but is larger in men than in women. And what he found was that the nucleus in gay men was smaller than in straight men. in fact, not significantly different from the size of the nucleus in women. So it wasn't hyper-male like the finger-length ratio it was? No. No. In that case, it indicated less, either less androgen exposure or less of a response to the antigen that was there.
Starting point is 00:28:35 And Simon got even more of an uproar than I did. Published his paper in science. And there were lots of people that were very skeptical, including some neuroscientific. but eventually another group replicated it. That's what I was going to ask, because I recall that the two major critiques of the paper, one was fair, in my opinion. It was that some of the postmortem samples were from people who had died of AIDS, and so AIDS has some known neurodegenerative effects that may or may not have impacted the samples,
Starting point is 00:29:07 although hopefully they control for that. And then as I recall, he also got some pushback because he is openly gay, and people accused him of agended. I didn't say gendered. I said agendered science. Yeah, that he was part of some conspiracy, a gay agenda to force Americans to regard people with same-sex orientation is somehow okay.
Starting point is 00:29:32 But a replication of the study from an independent group that presumably has no reason to be biased whatsoever. They were very skeptical of it. So that was William Blyer, who eventually, And there's an interesting aspect of it. It took them a long time to get a sample big enough because, you know, Simon, it was such a horrible time in AIDS epidemic. There were so many young men dying that Simon had no trouble finding enough brains to do the sample. And then as treatment got better, the death rates of HIV started going down.
Starting point is 00:30:10 And so it took longer for William Blyer to gather the samples, but eventually he didn't. And even though he was skeptical of it, he saw it too. The question about AIDS, I mean, Simon was able to address that in that he also had some straight men who had AIDS. And he didn't, you know, they weren't significantly different from other straight men. But, but, and so it was widely interpreted as proof that sexual orientation is not a choice, that it's something that happens to you. And of course, I don't think sexual orientation is a choice. That's true. But Simon himself made it clear that he could only look at this nucleus in adults, right? You can only look, it's so tiny. The sexually dimorphic nucleus is a preoptic area in humans. It's about the size
Starting point is 00:30:59 of a grain of sand, right? So you've got to have a microscope and you can only, there's no non-invasive way to look at it. And he pointed out that he didn't know if what, what the order of causation was. He didn't know if those men had been born with a smaller SDNPOA, and that's why they became gay, or did something else cause them to become gay and also cause the SDNPA to get smaller? And for the public, the idea that a nucleus might change its size in adulthood, maybe that seems kind of like, you know, unlikely. But as neuroscientists, we know that adult brains are changing all the time. In fact, even, Even in animals, Brad Cook showed that, you know, there's a nucleus, the medial amygdala.
Starting point is 00:31:46 There's sex difference there, but if you take away testosterone and males, sex difference goes away in just a matter of a few weeks. So Simon's work on the SDMPOA, also known as Ina 3. I won't bother with why. Unfortunately, I remember the full name. Because my brain, it's the interstitial nucleus of the anterior hypothalamus subregion 3. I'm not saying that to impress anyone. when you get to be 50, which I can now say that, you wonder why your hippocampus remember certain things that are like basically totally useless to remember.
Starting point is 00:32:17 I waste so many synapses on totally useless crap. But that's not, that's worth holding on to. You did well. So we don't know, it's a chicken and egg problem. We don't know if that happened, if they were gay because they had a small line of three, or do they have a small line of three because they're gay? So what I liked about Dennis's auto-acoustic emissions and is pretty good evidence that that happened well before they had a sexual orientation.
Starting point is 00:32:52 And the other thing I was liked about it is that, well, I mean, you can't imagine there's a social influence on digital. And nobody knew about this. So I wasn't worried that there were some little girls out there that looked at their hand to say, hmm, gee, that looks kind of masculine. Maybe I should be a lesbian, right? Because nobody knew this. Until your paper was published.
Starting point is 00:33:14 Yes, yeah. I mean, as I recall, there was some like schoolyard stuff of kids looking at each other's hands and trying to decide who was gay and who was straight. You know, every once in a while, to this day on the Internet, I'll look at it. And there'll be a little ad over there claiming to tell me something about my personality based on digit ratio length. And it's just like, you know, please, yeah, there's nothing to it. Don't waste your money, gang.
Starting point is 00:33:40 And there's an aspect of this, this fact that the group differences were there, but you can't tell about differences between individuals, that I think is the hardest thing for scientists to communicate to the public. Yeah. You have a really good way of explaining this to people because, and it's an important lesson just in reading statistics and making sense of data that I'd love for you to give an example of how this plays out, perhaps in a separate example.
Starting point is 00:34:07 Psychologists, they like to talk about a way of measuring how big a difference is between two groups. So this difference in digit ratios between men and women, it's a relatively small difference. It's like, well, we measure it in terms of how many standard deviations apart are the two means of the populations? The two averages. The two averages.
Starting point is 00:34:27 And to give an example of that, everyone knows about the sex difference in human height, right, among adults. So that's a huge sex difference. It's one where we're all aware of it. And if nobody had told us it was such a thing, we'd notice it after a while, right? And that's because those two averages and those two populations are about two standard deviations apart, the standard deviation being a measure of how much variability there is in something. So that's a huge sex difference.
Starting point is 00:34:57 And to give you an idea of what that means, if I had you grab a sample of a thousand people, and I'm going to tell you one thing about each one of them, and that's their height, that's all. And now I give you the job, you've got to guess what sex they are, and I can tell you what you want to do to maximize your hit rate. Everyone who is five feet, five and a half, you're going to say those are men, and if they're less than that, you're going to say they're women. and you'll be right about 80% of the time, which means you'll be wrong, almost 20% of the time, right? And so everyone, you can see that there's some predictive power there, but it's far from perfect.
Starting point is 00:35:40 Well, this sex difference in digit ratios is half a standard deviation, so a quarter of that. And so that means there's much more overlap. And we know that other things influence digit ratios, too, not just prenatal testosterone. And so this is why there's no predictive value. I mean, so anyone who looked at their hand while we were talking about this and got worried, I don't know anything about your particular prenatal testosterone level, no matter what your digit ratio is.
Starting point is 00:36:12 What about bisexuality, people who identify as attracted to both men and women? And maybe we ask about first, bisexual women than bisexual men. Is there a pattern in digit ratios that leads anywhere? I mean, in those days, we didn't have enough people that identified as bisexual to have a reasonable sample. And it's interesting. And that's something that's changed, right? I mean, if you do surveys now, especially among younger people, there are more people who report that they are bisexual than the word then. So I don't really have anything to say about them.
Starting point is 00:36:43 The one thing I will say is I'm sure that even among lesbians, there's more than one pathway, more than one developmental pathway to become a lesbian or to become a gay man, right? I don't think there's just one thing. That's not how human behavior. But you do think it's based on the data that it's biological. Based on that data, I think testosterone has a say, right? That it doesn't mean it's the whole package. Prenatal testosterone. Prenatal testosterone. And the reason I ask that is, I mean, there are conditions that are not uncommon where someone has a particularly stressful, long phase of development where there's every reason to believe that their androgens are impacted negatively.
Starting point is 00:37:24 Yes. There's also every reason to believe that there are stretches of development where androgens are increased. Like we know that people who do sort of a contact sport or engage in anything that requires like deliberate aggression. I realize that real martial artists. Competitiveness. No, competitive aggression.
Starting point is 00:37:44 know how to, you know, sort of gate their levels of aggression so that they're not, they're not like in a fury, right? But we know that certain types of activities, competition, et cetera, I mean, there's no question that those can increase androgen. So you can imagine there's some plasticity postnatally, and that could be before puberty. It could be during puberty. And so that's testosterone, the body, as you said, you said something that, even as a developmental neurobiologist, I don't think I'd ever heard, stated so clearly, and it's so important that the rate of brain development from birth until age 12 is at least as fast as it was before we're born. Yeah, I mean, the way to really bring that home is to compare human brain growth
Starting point is 00:38:32 and chimpanzee brain growth. So up until birth, the rate at which the brain size increases compared to body size is about the same in humans and chimps. And shortly after birth, the chimpanzee brain stops growing as fast and eventually asymptotes right away. The human brain continues that feverish fetal rate of growth until at least six years of age, maybe out there to 10 years of age. So people have pointed out that in a real sense, human beings, children are fetuses that are outside learning a whole bunch of stuff from other people.
Starting point is 00:39:11 That's the real distinctiveness of our species is, you know, we have this protracted childhood and really intense social learning. And as you say, a fetal rate of growth, even though we're not in the fetus anymore. So I guess for me, the idea that behavior, exposure to things, you know, and I don't want to get into valence of negative, positive, but sure, pesticides, but also, you know, school yard activities.
Starting point is 00:39:39 If you have, and we'll get to this, you know, five siblings, and it's very competitive. Who gets how much pizza? You know, I had one sibling, so it was a little bit, you know, there was competition, but it was different, right? You know, these things change hormones. Hormones change the brain. The brain, as you're explaining, can impact sexual preference. What's great about studying hormones and behavior, right, is that sometimes you can control
Starting point is 00:40:02 the hormone, in animals at least. But the hard thing about hormones and behavior that people don't understand is that behavior can affect hormones, as you say, in competitions, the winners afterwards are more likely to have higher testosterone and the losers will have lower. In elections, it's been shown that people whose candidate won the presidential election, their testosterone levels went up a little bit and the people whose candidate lost went down a little. And so you'll always have this cycle where the hormone alters the behavior, and then the behavior alters the hormone, and you always have to look for ways to try to pin down the order of effects, and, you know, not always easy. The only thing I know for sure is that the brain remains plastic all of our lives. Well, that statement is a significant one, because I also believe that the brain remains plastic throughout our lives.
Starting point is 00:40:58 it's always surprising to me that the hypothalamus remains plastic throughout our lives. And I think that's worth perhaps double-clicking on, so to speak. Because, you know, the idea that you can learn another language and your neocortex changes, or you can learn to juggle and your, you know, your neocort, your motor cortex change, your cerebellum changes. Okay. Like there's a lot of beautiful studies demonstrating that. But when I think about the hypothalamus, I think about it as something that's pretty hardwired.
Starting point is 00:41:28 by time puberty wraps up. But the more I learn, the more data that get published, the more surprised I am. I saw a paper just the other day that the neurons that control suppression of appetite, these POMC neurons in the RQ at nucleus, there's a population of them that are sort of undifferentiated that can become, let's just call it, pro-hunger, by expressing a different peptide, neuropeptide Y, and that there's a lot of late-stage plasticity. And this may explain why people who reach a certain level of obesity may actually find that they're hungrier despite not needing food. So it's fascinating to me how these deeper brain structures may actually remain plastic.
Starting point is 00:42:06 I think both your statements are true. I think it's probably true that the neocortex is more plastic than the hypothalamus, but it's a matter of relativity. And so as you say, the one thing we know is that there's plenty of plasticity there. The other thing I noticed, so I've gone to society for neuroscience meetings pretty regularly every year, since 1977. And after a while, I noticed something. Every year when I went to the neurosides meeting, the brain was more plastic than it was the year before, right?
Starting point is 00:42:33 I mean, because there are more and more of these demonstrations. And it's like, I, you know, I think synapses can come and go just about anywhere. And so hardwired, let's say there might be less plasticity in the hypothalamus. Surely so. But that doesn't mean there's none. As many of you know, I've been taking AG1 for nearly 15 years now. I discovered it way back in 2012, long before I ever had a podcast, and I've been taking it every day since.
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Starting point is 00:44:16 What are some of the other effects in human studies of behavior, impacting hormones that come to mind for you. I mean, it's been a while since we've touched into this, and we haven't done it much on this podcast. I mean, obviously competition, winners, losers, you explain the data there. What are some other scenarios? Just studies that have been striking to you or that have stood out over the years. No, I think for testosterone, I think the big ones have been competition, you know, between males. And no, I don't, you know, I mean, there's a stress response, but that's a whole other thing. What about sex behavior itself?
Starting point is 00:44:53 In animals, at least, we know that there's a relationship there, that in males, in males of most species, let's take rats, if you take away the testosterone, within a few weeks, they'll stop mounting altogether. And if you give them testosterone, after a few weeks, they start mounting again, right? So we know that that plasticity is there, and we know that it's driven by testosterone. But in animals where they're in charge of their own testosterone, we've known for a long time that if a male is exposed to the odors of a receptive female, that causes a spike in their testosterone. And so that's kind of preparing them for maybe I'll be lucky. Maybe there's something coming down the pike. And so we know that that's a reciprocal relationship when the animal's in charge of the hormone.
Starting point is 00:45:49 For the longest time, thanks to your textbooks. And by the way, folks, Mark has authored some of the most important textbooks on hormones and behavior, developmental neurobiology. He's a true scholar of the whole field. And so I'm immensely grateful to him that those textbooks have formed the backbone of a lot of solo episodes of the podcast. So, you know, the textbook version of male versus female sexual behavior has been a story of, you know, a story of, you know, the textbook version of male versus female sexual behavior has been a story of. about females having a circuit that goes from brain to body to control this thing they call lordosis, the arching of the lower back, the receptivity, the willingness to mate, and the males having a circuit that goes from brain to spinal cord to body involving arousal, erection, mounting, insertion, ejaculation. I mean, your lab and others has really parsed this right down to the details. And yet, of course, people have sex that way, but also other ways.
Starting point is 00:46:53 And so for a lot of people who aren't familiar with hormones and neural circuits and behavior, the sort of strict context kind of still forms the framework. You know, I mean, I've learned, and I'm now fortunate that this podcast has been around more than five years, so I no longer have to tap dance around things, right? So people will say, oh, well, you know, there's this lordosis behavior in the female. she's receptive or not. He mounts, et cetera. And then there's gay men who have to have sex a certain way that mimics the female sex pattern of behavior. And so people do this one to one, right? And I think that it's understandable why they do that if they're not educated. But how should we make
Starting point is 00:47:33 sense of these biological circuits that are in the textbooks that define stereotyped, literally motor behavior? It's almost like saying like females have sex this way with males. Males have sex this way with females. But then the caveat is always like, oh, but in humans, all that goes away. And there's these like bonobos that are a little bit more like humans. So did we waste all our time studying that stuff? I mean, really. And you're getting at exactly what every textbook author has to deal with, right? Which is, you know, as the old joke go, you look where the light is, right? So we know so much more about the circuits that are involved in the motor behaviors because they're relatively easy to trace and relatively easy to manipulate and relatively easy to study. We know lots about the motor
Starting point is 00:48:20 patterns in animals. We know a lot less about the motivational patterns in animals, which in human sexual behavior is, I mean, in many ways, that's the whole show. You know, that's really what's, and we don't really have good animal models of libido, right? And this was brought home to me, many years ago now, I was on a session of 60 minutes, the CBS News program. And Leslie Stahl was there in our lab. I mean, the producers had called me up and said, you know, can you show us a way that early testosterone exposure changes behavior permanently? And I'm sure, I can do that, give me some time. So I went to the lab and castrated a bunch of rats on the day of birth. I know how to do that. I'm not proud of it, but I know how to do that.
Starting point is 00:49:13 And they came three months later. And so I showed them those motor patterns you talk about. So here's a typical female. I've given her hormones, estrogen and progesterone. So I know she's going to be receptive. And here's a male rat that I know has had lots of experience copulating. And Leslie immediately dubbed him Romeo. Okay, well, this is Romeo.
Starting point is 00:49:38 And she hates rats, by the way. She was very brave. So I drop a female on top of Romeo, and he starts mounting, and she shows theidosis posture. It's all beautiful and easy. And we do that several times. And now I'm going to drop a male, control male in. And Romeo, of course, you know, you don't know unless you try. He mounts several times, and the male rat acts like nothing's going on.
Starting point is 00:50:03 I mean, it's just a bored thing on earth, and Romeo eventually gives up. Now I drop into the cage, a male rat who I castrated on the day of birth 90 days before, and I've given him the same hormones I gave the female to make her receptive. Romeo hops on, and sure enough, a beautiful lordosis, right, of the sort that the control male never showed. So here this neonatally castrated male is showing very female-like patterns. and Ms. Stahl kept asking me, would you say this is a gay rat? And it's, you know, I'm sitting there, and I'm definitely in a tough spot because I don't think my rats have an orientation. I mean, we just saw Romeo happily mount any rat I threw in the cage because what do you know, you know, try your luck.
Starting point is 00:50:56 And so, you know, she asked me, said, and I knew she wanted me to say that, but I said, what I would say, I don't remember exactly what ended up in the final. What I would say is this is a rat whose sexual behavior has been permanently changed because of something that happened to him a long time ago at the very beginning of development. And really that's the best I can do in terms of any rat model of sexual orientation. I don't think my rats have a sexual orientation. If I give the female those hormones, she's going to show uridosis to whoever mounts her. And my male rat, he will mount any rat he comes across just in case he gets a lordosis out of him. Well, good on you for not getting corralled into giving a particular answer.
Starting point is 00:51:44 I've recently joined CBS as a correspondent. And if we have this conversation on 60 minutes, I promise to not try and force an answer. Romeo is an interesting case because I think for most people, including myself, I thought that you were going to say that Romeo was willing to try to mount a female. If she was receptive, he would mate. If not, he wouldn't. But I was surprised that he would try to mount a male as well. That doesn't align, at least with my experience, of male human behavior.
Starting point is 00:52:18 Certainly not. That's right. This is the thing that's distinctive about humans is we're not actually that particular about what particular behaviors we engage in, what motor behaviors. And we're overwhelmingly interested in who our partner is. That is an overriding concern that I don't think my rats have. I think few animals do. You're the anthropologist from Mars, and I tell you, here's a person that 50%, here's, whoever's the sexiest man alive this year, People Magazine.
Starting point is 00:52:54 I don't know who that happens to be. This is an interesting discussion altogether because there's this people have been lining up the images of these people and claiming that they're sort of like this effeminate drift that takes us back to a time in the early 90s when there was this sort of revision about male facial. We can get back to that. But yeah, okay. It's not the point being that it's not fixed. Yes.
Starting point is 00:53:17 Yeah. Well, whoever, let's say is George Clooney. So here's someone that half the planet believes is an idea. ideal sexual partner, right? But the other half of the planet finds him totally unacceptable, even if the behaviors they engaged in would be pretty much the same. And so, you know, in terms of positions and who's doing what to who's genitalia, et cetera, I mean, for most people, it isn't that there has to be one particular act, I suppose there's some, but for most people, there may be a variety of acts that they want to be engaged in with that other person.
Starting point is 00:53:57 And their overwhelming concern is the gender of that other person or the sex of that other person. You know, it's hard to have an animal model of that. I actually do know one example in sheep, if you want to talk about this. Of all things. Yes. Oh, I noticed it. So Chuck Roselli out of Oregon, he's the one that studied this very carefully. I guess shepherds have known for ages that in any herd there are some rams who will not mount a female ever and keep mounting other males.
Starting point is 00:54:34 And of course, to maintain a shepherd, to maintain a herd, you don't need every male to reproduce. So, but in the old days, they got those males got sent off to slaughter, right? Well, hearing these rumors, Chuck did these tests. where he would put a bunch of females that are in stocks so they can't move and they're all ready for mating and he put a ram in with them and most rams of course will mount the females he puts in these rams that that prefer males if there's a variety of sheep's butt sticking out at him out at him, he'll mount males, including sometimes, you know, having intermission through the anus, and all the way to ejaculation, and he never mounts a female. In some cases, they'll have one of
Starting point is 00:55:30 these, I'm going to call them gay rams. I think they have an orientation. He'll put this gay ram where there's a dozen females, and he might be in that paddock for 12 hours and never mount a single female. Highly unusual for male rams. These are not typical ram. It's like a small percentage of population. And I don't know how to explain that. I mean, you would think that these gay Rams that, well, you know, an ejaculation is an ejaculation, right?
Starting point is 00:55:58 And orgasms is an orgasm. I presume they have orgas. You would think that at some point of the, well, there's nothing else to do in here. I'll mount one of these ewes, and they never do. And I don't know how you can explain that, except that there's some aversive component that Rams do care about. the sex of their partner and that and that for these gay Rams there's some aversive component to that by the way Chuck told me not too long ago there's a
Starting point is 00:56:26 company that has identified these gay Rams and decided that instead of sending them off to slaughter they're gonna harvest their wool and sell them as and make them into clothing so you can buy you can buy wool clothing that came from gay Rams and know that you save them from the slaughterhouse? There's no response that's appropriate to that statement. And apparently they, you know, they're out of stock. So it's been a big success.
Starting point is 00:56:56 Actually, I can think about 50 different responses to that, none of which are appropriate or have any real conceptual importance. So I won't say. Fascinating because Rams, while, of course, they have sociodynamics, presumably there isn't a pressure, independent of reproductive pressure, to be a gay ram or a straight ram. And I guess I left off the kicker,
Starting point is 00:57:25 which is Chuck eventually dissected the preoptic areas of these various rams, and he found a difference between the preoptic area of gay rams and straight rams, a difference in how they process testosterone. And exactly that part of the brain, the preoptic area where Simon saw a difference between gay and straight men. So there may be something about the hypothalamus, the preoptic area, that has something to do
Starting point is 00:57:52 with orientation if we're talking about an organism as complicated enough to have an orientation, including sheep. This is a particularly nice moment, not just for this episode, but for the entire podcast arc, because there are these moments that come up every once in a while where a larger principle shows up in a new way that I think is really important for people to understand. Across neuroscience, we see this push-pull, right? A flexor muscle like the bicep, when it flexes, the tricep relaxes.
Starting point is 00:58:28 When the tricep flexes, the bicep relax, these antagonistic relationships. You see this in the hunger circuit. I mentioned one earlier. Like hunger and feeling full are, they're like a push-up. pole. They're like a seesaw. And you see this over and over and over again. It's a, it's a very consistent theme of a brain function. And you said something that I was not aware of, but makes perfect sense. I just wasn't aware that there were, you know, data at the level you describe,
Starting point is 00:58:55 which is clearly there's an appetitive aspect to sex behavior, heterosexual males wanting to have sex with females, heterosexual females wanting to have sex with males and so on, every derivation there. There's a desire in species where there's strong pheromone and odor determination and receptivity stuff gets played out that way. It looks one way. In humans, it may have some of that, but it plays out different way. Receptivity is communicated differently, although odor may be very important in ways we don't quite fully understand. But this idea that there's an aversive aspect to it, right? I think this is important, and it's something that I have not heard discussed before. And I think that sociologically it has relevance because I think that there's so many
Starting point is 00:59:41 different aspects to the notion that our species, humans, come in gay and straight and perhaps bisexual varieties. We know that's true. Clearly. But there is this not uncommon theme whereby many people. I can only, you know, say many people, right, not all, that the concept of mating with same sex is aversive to them. And that has shaped a lot of the landscape around this. And I'm not trying to get political here. It's just, I think it's worth acknowledging that that may be a real phenomenon too. I'm not trying to justify mistreatment of anybody. But I think that we're never going to get where we want to go as a species societally until we really, really, at least understand the biology and how to work with it.
Starting point is 01:00:31 And so the idea that same-sex sex, right, would be aversive as an idea to people. Some people are like, oh, well, they haven't been educated. Okay, perhaps. But there may be a biological basis for that. I think the data are still out. But I think it's, to me at least, it's pretty clear that for men at least, there's an asymmetry here. That experiment where I said, you know, who wants to have sex with George Clooney? Half the population says, sure, the other half population, never.
Starting point is 01:01:07 If we reverse the experiment, what percentage want to have sex with Margot Obie? And, yeah, half the population, the men would see there's a very desirable sexual partner. But, you know, the women too would, many women would also, would at least consider the idea of having sex. with her. And we know there are plenty of women who are straight in one part of their lives, and later they fall in love with a woman, and now they feel like they're gay, right? So females, women, are more plastic in terms of their sexual longings and sexual orientation than men are. I'll be a little more specific. I think it's among males where sometimes, for many males, not all, there's an aversive idea, that the idea of having sex with the same-sex
Starting point is 01:02:02 partner is aversive. Now, of course, context matters, right? There's same-sex happening in prisons all the time when, you know, if the conditions are enough. And I don't know where that aversive component came from. It could be that our society, maybe it's all socially inculcated, you know, again, before we're aware of it at all. But I, you know, I think there's also at least the possibility that there's a biological component to it. And I think that's what Chuck was getting at in that here's this difference in the brain. He doesn't know when the difference happened in their pre-optic areas, but it seems to correlate with this idea that maybe these gay Rams, no, they're not interested in having sex with her. It's aversive to them.
Starting point is 01:02:50 It's aversive, yeah. There's no other way to – I can't – I don't know any other way to explain how they're. choose never to never once mount a female. I feel like that the acknowledgement of an aversive pathway for sexual partner choice is as important as the acknowledgement of biological correlates of homosexuality. Yeah. Because if this sort of conversation is ever to advance past the sort of like, okay, what's okay to say now, that we're willing to say now, trust in science disappears.
Starting point is 01:03:25 I really believe that. Now, of course, the problem is that people leverage fragments of what they hear in order to make arguments in favor of whatever stance they have. And that's the complication. That's why I like long form, because no matter what gets pulled out, we can go back to the full conversation. And this makes you old-fashioned because that's not the world. I mean, our world seems to be hurtling towards this world. World of snippets. People will notice that we have not used the word gender. We're talking about biological sex and sex the act. And we're talking about male versus female partner choice. And we're talking about a desire for one or the other and an aversion to one or the other. And I think the aversion piece is an important theme. So here's a hypothesis.
Starting point is 01:04:12 If I can come do a sabbatical. I'm due for a sabbatical at some point. It may be that in male humans that there's a pathway. or a molecule that serves as an aversive to sex with other men circuit, peptides, neurons, etc., that suppresses sexual desire and activates some level of disgust. I'm going to just say it bluntly. It might not be the same disgust that they would experience to something more aversive, but okay. And that in women, there is no such pathway.
Starting point is 01:04:44 There's either desire for women or desire for men. But as you said, statistically, women are more open, on average, to same-sex interactions. And it may be because there's no aversive signal or the aversive signal has a less robust circuit. To me, that would explain these differences, these sex differences in who people are willing to have sex with. Your hypothesis fits the data. I mean, it is true that in the, like the early 90s, for instance, when the first, gay characters were on television, like the first real world, and I'm really dating myself here, and subsequent characters started to dismantle some of the stereotypes that had been seen in
Starting point is 01:05:30 like comedies in the 80s and things like that of the effeminate gay man. Yeah. Right? What you saw was indeed that heterosexual women, as far as we know, seemed to be more, like, generally accepting of gay men before heterosexual men embraced. that as typical. That's my impression, too. I think it's pretty clear. Yeah. And then there's a societal shift. And then it sort of becomes like, you know, like if you, like I spend some time on X, formerly known as Twitter, right? And there's some gay political accounts. And you just kind of
Starting point is 01:06:08 notice, like, it's just people are like comfortable with it. Men and women seem to be comfortable with that, right? I mean, of course, you don't see a lot of attacks now. That's very different than what you would have observed, for instance, in like the late 80s or early 90s, right? Anyway, I think these are important biological phenomenon, this notion of an aversive pathway. You could imagine where societal standards or community standards or household standards might, you know, amplify or reduce, like, the sort of expression of these things. I'm sure they do.
Starting point is 01:06:44 Yeah. And I'm sure, you know, cultures, you know, can amplify or. reduce that component. The question is, you know, to what extent? I mean, and I don't think we know. One thing that we haven't talked about, and it is a small percentage of people, but it's something that people think about,
Starting point is 01:07:04 is this notion of sort of neither here nor there, kind of mixed sex, right? Is there a biological correlate of that? A graduate student my year, when you were my professor, Yes. Nikki Osipka, Nicola Osipka, who was already famous for training dogs for the Beastmaster show. It's amazing.
Starting point is 01:07:28 And had very well-behaved dogs that she would bring out everywhere with her. Studied a species of mole in Tilden Park that could transdifferentiate its testes into ovaries and back again. And I thought, well, that's like alien weird levels of stuff. but she would occasionally go over to UCSF when babies were born that were sort of back then they called them, no one uses this language now, pseudohermaphrodite. Yes. What is the deal with exposure to prenatal androgens and neither clearly here nor there a genitalia? Yeah, so in most of those cases, we're talking about congenital adrenal hyperplasia, also known as CAH.
Starting point is 01:08:11 And the congenital means it's present at birth, and the adrenal hyperplasia is, is referring to the fact that the adrenal glands are slightly larger. And the reason they're slightly larger in this case is because these are individuals where the fetus itself is not able to make some of the adrenal steroids that are important for staying healthy. And so the brain detecting, hey, where are the adrenal steroids that we need here, drives the pituitary to tell the adrenal gland,
Starting point is 01:08:44 hey, we need more steroids. The adrenal gland gets the message, it hypertrophies, but the machinery isn't there to make those steroids, and so instead the adrenal gland makes testosterone and other androgens. And actually, this can happen in either XX or XY individuals. And in X, Y individuals, people might not notice, but in XX individuals, what that means is that prenatally, her genitalia are being exposed to more testosterone than is typical. And so under the influence of this extra testosterone, the clitoris may grow to be bigger than the typical clitoris. In some cases, in extreme cases, the phallus looks like a penis.
Starting point is 01:09:33 And the skin around that area that would normally form the labia, again, there might be enough testosterone that it starts to look like a scrotum, except, of course, there are no testes inside there because this is an XX individual. So these individuals are identified at birth, typically, especially in XX individuals. And there's an easy treatment, which is, oh, they can't make, you know, you do the tests and you say, oh, they can't make adrenal steroids, so we'll give them some. And so for the rest of their lives, they take adrenal steroids orally and get the benefits of that. And that shuts off the hyperactive adrenal glands. So it shuts off. It shuts the role of the output of testosterone.
Starting point is 01:10:17 So this is what's known as an intersex phenotype. And yes, you're right. In the older literature, they were sometimes known as pseudohermaphrodite, with the idea being whether a hermaphrodite is an individual that can function and reproduce either as a male or female. And so supposedly they were pseudo because they can't do that, because they have only ovaries. Well, you can imagine, first of all,
Starting point is 01:10:43 being called hermaphrodite, nobody like that. And if you ask them, well, does it better if I put this pseudo at the beginning? Does that make you feel like you're being less stigmatized? No. But a much more accurate description is to say that it's intersex. They have a phallus that's somewhere between a cuddrus and a penis, and the skin around there is sort of like a scrotum and sort of like labia. So in the old days, once this got recognized, it was standard procedure to tell the parents, oh, this is an emergency.
Starting point is 01:11:21 We need to do cosmetic surgery. We need to do surgery to make this little girl look like all the other little girls. You know, sometimes this surgery was, you know, there could sometimes be successful or not. Indeed, they knew how to make her look like other girls. But many of those intersex folks, when they grew up, were pretty angry that someone had done this surgery on them that wasn't needed medically, right? They were already taken care of the problem with the exogenous adrenal steroids. And so who asked you to deal with my, you know, to do surgery on my clitoris? In some cases, the tip of the clitoris was missing.
Starting point is 01:12:04 And so these women grew up and were an orgasmic because they couldn't get the stimulation. that they normally would have had. These days, there's much more, thanks to the activists like Cheryl Chase and others who started getting the pediatrician's attention, hey, you need to think about that. You're doing elective surgery on an infant who cannot possibly have informed consent. And so these days, there's more of a wait-and-see attitude, which I think is absolutely. So wait until they're grown up and ask them then if they want to have surgery. and my guess is most will say no.
Starting point is 01:12:40 I think that's been the pattern so far. So these are females who are exposed to more testosterone than other females. So does that mean that they're going to be attracted to women when they grow up? And the answer is, well, interestingly, if you look at groups of women with CAH, they are more likely to be same-sex attracted, to be lesbians, than the population at large. But most of them are straight. But what's interesting about that is the older they get, as you keep surveying them, the higher the percentage of them, the report having a lesbian orientation. So it's possible, first of all, that indicates that, yeah, maybe prenatal testosterone increases the odds of them being lesbians when they grow up.
Starting point is 01:13:28 And you also wonder, well, how many of them always had that same-sex attraction, but, you know, were following the past. halfway society laid out for them. And then as they get older, they say, well, no, screw this. I know, I know who I'm attracted to. I don't have to fit the heterosexual mold. And so it's, you know, that's entirely consistent with the idea that prenatal testosterone makes you more likely to be attracted to women when you grow up. There's another syndrome that I know you've talked about, which is androgen insensitivity syndrome, sometimes abbreviated AIS. And it turns out But the gene for the angri receptor that responds to testosterone and other androgens is on the X chromosome.
Starting point is 01:14:12 And it may sometimes be that a woman will have an X chromosome that has a copy of the end receptor gene that doesn't work. And if she passes that X chromosome onto a daughter, then she's sort of duplicated herself. What's interesting is when that X chromosome is given to a son. In other words, that egg with an X chromosome that has a dysfunctional copy of the copy of the antoreseptor gene. If it gets fertilized by a Y-bearing sperm, now we have an XY individual. And as you've explained clearly in your basics podcasts, we know what will happen in development. The Y chromosome will mean that the indifferent GONAD will develop as testes.
Starting point is 01:14:54 The testes will secrete two hormones that are going to guide sexual differentiation in the periphery, one of them being anti-malarian hormone, which is going to suppress the development of the malaria ducks, and therefore no overduct, no uterus will form. And the testis will also release testosterone, which normally would masculinize the body. But in this case, because there's no functional antireceptor to respond to it, the testosterone goes round and round, but the body doesn't respond. And so the wolfian ducks don't develop. The periphery looks like a typical female. And these individuals, when they're born, often are not identified. Because the baby's born. The doctor does that very careful analysis by looking between the legs and says,
Starting point is 01:15:40 congratulations, you have a girl, and they grow up to be girls undetected. And they come to a doctor's attention when puberty happens, and all their classmates are having their period, but she's not. And so she'll eventually go to an OB-GYN, who will first do an exam, eventually. vaginal exam, and he'll notice that the vagina is relatively short because the inner part of the vagina is normally derived from the malarian ducks. Well, in this woman, in this teenage girl, the malaria ducks never developed because of anti-malarian hormone. So there'll be no cervix that can be seen in the exam. And if he takes blood plasma levels, he'll see that this very feminine-looking girl, teenage girl, has very high levels of testosterone. And presumably testes. And if he does a
Starting point is 01:16:38 karyotype, he'll see that she has an X, Y, carotype. And yes, there are testes in there, typically in the abdomen. And they're releasing lots of testosterone because there's no negative feedback to tell the brain, you know, hey, you can stop sending signals to the testes now. In these cases, you can ask, well, what's the sexual orientation of these women? And the vast majority of them grow up to be straight. They are attracted to men, and they might be very, they're often very interested in having a family. Of course, they can't carry children themselves, but they can adopt and things like that. And so they're very much feminine, very straight women. But they're X, Y's. So the question is, unfortunately, in terms of understanding whether prenatal
Starting point is 01:17:27 testosterone alters our sexual orientation, these individuals aren't useful to us because we don't know if they're straight women because their brains could never respond to the prenatal testosterone or are they straight women because they were raised as girls and socialized to be attracted to men. It's a fascinating syndrome and there's at least one woman with AIS who's self-identified who's a successful model. And there's another woman who wrote a memoir that's quite good. And what's interesting about it,
Starting point is 01:18:02 when there's no testosterone response, they have very feminine faces, very feminine bodies. And so they're frankly quite attractive as women. I'd like to take a quick break and acknowledge our sponsor, Function. Function provides over 160 advanced lab tests to give you a clear snapshot
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Starting point is 01:19:14 but now with function, it's extremely easy and affordable. To learn more, visit functionhealth.com slash Huberman. and use the code Huberman for a $50 credit towards your membership. I'm realizing, I'm drawing a model over here, whereby we've got, again, accelerators and breaks. And I think we've got different axes. You know, I'm not trying to split hairs here, but I think for people who want to understand how hormones, sex, and behavior, sexual orientation fit together, it's very useful to think about, okay, you've got chromosomes that drive, you know, are typical notions of male versus female, and you're providing some important caveats
Starting point is 01:19:58 where the body appears one way, but it's an X, Y, you know, and there's almost every derivation of this has been observed, although not at a very high frequency. And then you've got choice of same versus other in terms of orientation, a key role of prenatal testosterone there. maybe some cultural or other types of plasticity that might be biased more toward the female side. It seems that way based on what you're saying. I'm willing to say it if you're not. It does seem that way.
Starting point is 01:20:30 There's an aversive signal that certainly in male sheep and other species. And that matches my observations as a 50-year-old male who grew up in northern Kentucky. California and, you know, I mean, again, in this era. And the joke being that I can only speak from my own reference point on this. And then we have a bunch of different things about partner preference and that at some point, it almost seems like it departs from, well, it certainly departs from our sort of linear like, okay, girls like boys, boys like girls, testosterone makes boys, estrogen makes growth. We're nowhere near there.
Starting point is 01:21:15 We've left that station a long time ago. Exactly. And at the same time, we arrive at a place where I think we need better languaging to separate these axes because it is very confusing for people. And so that would be very useful if the fields of neuroscience and psychology would start to embrace the real world realities of, of because I actually think the lack of specificity of talking about orientation versus biological sex and these and these other aspects have led. I think that's the source of a lot of conflict actually.
Starting point is 01:21:53 Anyway, that's an editorial for another time. In terms of biological impact on sexual orientation, one of the more striking findings that you've been talking about for a number of years that just kind of shocks at first, but then you get a lot of nods from people, is this idea that the larger the number of older brothers that a male has, the higher the probability that he is gay. It's been seen over and over. I mean, it's really one of the rock-solid findings in human sexuality that was first noticed by Ray Blanchard at Toronto and has been seen in many populations all over the world. So the way to emphasize the difference is if a baby boy is born today, if he has no older brothers, his odds of being gay when he grows up is about 2%, right? Pretty low. But if he had
Starting point is 01:22:52 one older brother, his odds go up by a third. Okay, 2.6. And if he has two older brothers, they go up a third again. All right. Now we're at 3.5. It turns out you've got to have like a dozen older brothers just to have a 50-50 chance from the same mother. Right. So we know that it's not, you know, what they call now blended family or so this is. We'll get to those in a moment. But but this is what you see. So you get a big population of men. Here's here's a big population to have one older brother. How many are gay? And it's a small number. And the number they have two, still small number, but more. And, you know, how do you explain that? We saw it when we did the survey.
Starting point is 01:23:34 I don't know if you remember, we also ask people how many older brothers and sisters they had and how many younger brothers and sisters they had. So it turns out in the general population, they're about 105 boys born for every 100 girls, right? That's also very consistent. 105 boys born for every 100 girls. That's right. So there's – or put another way, if you want – I can guess the sex of any baby that's going to be born, and I can be right more than 50% of the time, because I'm always going to guess boy, right? Because 51% of the time, it'll be a boy.
Starting point is 01:24:08 For straight men, you total up all the older brothers they have and all the older sisters, and there's a ratio of about 105 older brothers to 100 older sisters. For the gay men, it turned out there were 140 older brothers for every 100 sisters. Help frame that statistic for people. So you gave us the one older brother what the probability was. It's a third increase. You go from 2% to 2.6. Is it a linear increase?
Starting point is 01:24:38 As you increase the number of older brothers, you just start increasing the probability with every older brother, or is it sort of a step function? It is, in fact, a linear progression. So at that rate, so Ray's worked that out. Of course, it's hard to find men that have had more than four or five older brothers, especially these days. But it turns out in the Kinsey surveys, Ray went to the Kinsey surveys. way back then, you know, those interviews were incredibly thorough.
Starting point is 01:25:05 And so they have a record of how many siblings of each sex every one of those men had. And you can see it there too. And it's another one of these cases where I tell you this and you tell me, well, I know somebody who has two older brothers and they're gay. Is that why? Or I know somebody with three older brothers and they're not gay. So you tell me, oh, I know someone who has two older brothers and he's gay. Is that why he's gay? And I really can't tell you.
Starting point is 01:25:31 There's no way to know because, in fact, most men with two older brothers are straight, right? Again, it's one of these instances where it gives you no predictive power about one individual, why they are gay. Ray Blanchard has done the statistics, and their estimate is of all the population of gay men, about one and seven, are gay because their mother carried brothers before them. And what I mean is those same men with the same genotype, same genes, if their mom hadn't had older brothers before them, they'd be straight today. Statistically speaking. Statistically, but you know, you show me a picture of the gay men's chorus, and I can't point out which man is gay because of that, because there are other factors that can influence whether someone grows up to be gay. So again, it's one of these things where the statistical comparison is of great theoretical importance, even though it offers no predictive value for a given individual.
Starting point is 01:26:34 So we know that males engage in much more rough and tumble play when they're younger, just like rats, just like monkeys. This is a fact. It's related to testosterone exposure. If a boy has older brothers, there's a decent chance. he's engaging in more of that than if he has a sister. And given what you said earlier that in humans, the brain continues to develop at a massively accelerated rate,
Starting point is 01:27:01 even after birth up to age six, testosterone has an influence, behavior impacts testosterone. Okay, they're not in puberty yet, but you could imagine this has an impact. So the experiment becomes for boys that had two or more older brothers, but were not raised with those older brothers, does the effect hold of them having a statistically greater probability of being gay? It's a beautiful hypothesis.
Starting point is 01:27:28 And you first hear about this. That's the first thing you think. Well, maybe the younger brother got bullied or... Or beat up as older brothers. Maybe the older brother somehow inhibited the younger brother from developing in a full masculine fashion. But it turns out Tony Bogart started looking at these data. And he started asking, well, what about... stepbrothers. Do older stepbrothers make any difference in the odds of sexual orientation? And the
Starting point is 01:27:54 answer was a clear no. On the other hand, older brothers who came from the same mother, but were raised apart, had just as much of an effect as those that were raised with. So it does not seem to be socially mediated. In fact, Ray Blanchard and Tony Bogart have come up with a very plausible hypothesis called the maternal immunization hypothesis. And it runs something like this that, you know, the first time a mother carries a son, that son is carrying some genes that her immune system has never seen before. All the genes on the Y chromosome, there's no way her immune system could have seen it. And as long as that first son is in utero, her immune system never sees it. But Inevitably at birth, whether it's cesarean section or vaginal delivery, there's always blood and there's always mixing of blood.
Starting point is 01:28:49 And so at that point, the mother's immune system is going to see these male-specific antigens that it's never seen before. Of course, it's going to regard it as an invader, and it's going to start making antibodies to it. So their hypothesis is that each time a woman delivers another son, her immune system is going to generate more of these antibodies. And if she has a subsequent son, antibodies cross the placenta just fine. And so, in fact, the placenta very actively sends antibodies across to protect the young. And so that would mean that her antibodies are going into this third son and somehow altering the development of their brain. And the strong evidence they found in favor of this is that in women who have sons where there's this pattern that looks like that might have. happen. It turns out they have higher levels than control mothers of antibodies to a male
Starting point is 01:29:49 specific antigen, quite specifically, an antigen to a protein called neural ligion 4Y. So neurolegation molecule. Exactly. You know that neural ligands are important for synapse formation. And it turns out there's several copies, not unusual in humans. And this one, neurolegal 4, there's one on the X chromosome and one and Y chromosome, and they're slightly different. And so the fact that these mothers are making antibodies to this male-specific antigen, and that in their particular family it looks like subsequent sons who are more likely to be gay, you can imagine that's what's going on, that her immune system has perturbed the development of that subsequent son enough that when they grow up, they're more likely to be gay.
Starting point is 01:30:37 Whatever the mechanism is, it has to be that it's the mother's body that is remembering how many sons she's carried before them, right? And it's got to be the mother's body that somehow is doing something to perturb the development of her subsequent sons to make them more likely to be gay. It's a fascinating idea. And it also gets at that same theme that I mentioned before. There are lots of different developmental pathways to end up being gay or to end up being straight. And there isn't going to be one cause of anything in human behavior and certainly not of sexual orientation. But I think the evidence is looking pretty strong that for women at least, prenatal testosterone does have a say. And we know that in men, the mother's body has a say in whether they're going to be gay or straight when they grow up.
Starting point is 01:31:28 The result is so cool because once again, it spits in the face of the, these like kind of reflexive assumptions, for instance, you could imagine. And I probably grew up hearing like, oh, you know, he was raised around a lot of girls or something, you know, had a lot of sisters or he had an older sister or three, right? Or dad left the house. You know, I mean, this didn't happen so much in the 70s and 80s, but it was more frequent in the 90s. You know, back then it was called broken homes. Now people will be like, what are you talking about? Like, everyone knows somebody divorced, right? So, but back then it was more rare. And there were. this idea like lack of male influence. And of course, there are important, I believe,
Starting point is 01:32:10 gender-specific influences on kids in terms of upbringing, but in terms of the stereotype that seems to have largely dissipated, but that, you know, like having an older sister or three would make a son more likely be gay. It's exactly the opposite when you look at the biology. Yeah, I mean, Ray's looked at that very carefully. And so older sisters don't matter. And neither do younger sisters. And here's the other. that younger brothers don't matter, right? So no matter how many younger brothers you have, that doesn't change your odds of being gay when you grow up.
Starting point is 01:32:42 So that's why I say it's got to be the mother's body that is remembering, and it doesn't seem to be socially mediated. It is independent of that. It is nature having its say. Males with congenital adrenal adrenal hyperplasia. We didn't talk about that. And perhaps more important is to talk about males and females with congenital adrenal adrenal hyperplasia but are heterozygos. So they have one functional copy,
Starting point is 01:33:08 one non-functional copy. And the reason I raise this is that it's very common. It's one in 12. Huh. I didn't know. One in 12, which seems like an outrageously high number, but it's one of the things that is immediately screened for, maybe not as much as some other blood-related diseases and things like that. No, I didn't know that. But I can see, I mean, you have to remember, Actually, there are several different genetic mutations along the pathway of making adrenal steroids that can go wrong. And so there are several steps that have to be there for the mega-drenal steroids. So, number one, there's more than one site where the mutations would be carried.
Starting point is 01:33:49 And, of course, the heterozygotes may have no symptoms whatsoever. And so they may reproduce just fine. We know this. Sorry, I should be clear, because people are probably thinking, wow, one in 12. both males and females that carry one mutant copy of CAH are capable of healthy reproduction. There are some hypomorphic phenotypes. Some people make more androgens. Some people have a sustained stress response.
Starting point is 01:34:17 It's not very well studied, but it is very common, which I found interesting. Another reason why the carriers are so common is because typically there's no phenotype. Or if there is, it's subtle and so it doesn't come to the attention of any physicians. it's only when two defective copies of the gene come together in one offspring that there's no adrenal steroid production at all. And then things happen enough to get the attention of the doctors. Yeah, I've looked into this and it does seem like one mutant copy of CEH is you find it just statistically more frequent in professions or sports where there's a requirement for long
Starting point is 01:34:57 duration stress tolerance, which makes sense. Right? I mean, so some of these genes could confer an advantage. Yes. Some could confer a disadvantage in different settings. And that there might be a heterozygote advantage. I mean, you know, the classic example of sickle cell anemia, right, where being a heterozygote for that gene confers an advantage if there's malaria in the area, you'll be less likely
Starting point is 01:35:21 to succumb. Things go wrong when two copies come together in one individual, and that's the same thing. That's when the blood cells are especially affected. And things go wrong when an offspring gets two such copies, which is relatively rare, but it does happen. And in that case, then the offspring is very sick. Did you ever do the head transplantation experiment on the finches? That's amazing what sort of a memory you have.
Starting point is 01:35:47 No, no, I never did. You want to explain what this was? Because I'm not going to do it correctly, but I remember you wanted to do an experiment where you were going to transplant finch heads. And I thought it was the coolest experiment ever because it was going to be done as embryos. So no, it was not taking heads off of birds. It was an embryo experiment. But I think we should talk about the backdrop of this.
Starting point is 01:36:11 Male birds of certain species sing. Female birds don't. Right. So you wanted to embryonically put a female head on a male body, a male finch head on a female body. You want to swap head bodies of these embryos. Tell us the experiment. I'm certainly looking like the mad scientist. Well, let me tell.
Starting point is 01:36:34 Wait, wait, wait, hold on. Crazier things have been done with U.S. tax dollars, like rainbow mice, mice that glow, you know, 215 different fluorescent colors to identify different cell types. I mean, I could go on and on and on. I think this experiment has a purpose to get out a principle that can't be under any other way, so it's not just tinkering for the sake of tinkering. In fact, people do those sorts of transplants and birds. So a very famous neuroscientist from France, Nicole LaDuran, did these experiments where she would
Starting point is 01:37:08 open up chick embryos and quail embryos, and she could scoop out part of the nervous system from one and implanted in the other, and she'd know when she had done it right, she had a way of telling the cells apart under microscope. Plus, when they grew up, here you'd have this white leghorn chicken with a streak of brown feathers, right where she... Was it called a quicken? Sorry, couldn't help myself. Here you'd have this white leghorn chicken with a streak of brown feathers in the middle
Starting point is 01:37:39 that were derived from the quail. And so it is possible to do those sorts of swaps. And, of course, this is what's so great about working with birds, is their embryos are, you know, easy to get to for the first 21 days or so. So people had done those sorts of experiments. There was a question about sexual differentiation of the brain in birds. Because the, and I'll tell you why it turned out I didn't need to do that experiment, and it wouldn't have shown what we wanted.
Starting point is 01:38:11 That is, so there are, sometimes you'll see in the news, someone will find a genandromorph in birds, yep. Gen andromorpe. So half female, gen, and half male, Andro. And when it happens in Cardinals, for example, it's like the animal's been split down the middle. No. Yes. Where the one side is the bright red of a male, the crest, et cetera, and the other side isn't, right? So these occur occasionally. And our best understanding of what happened there, first of all, the sex chromosomes are a little different in birds than mammals. I'm going to gloss over that. But our best. understanding of what happened there is this is the case where two embryos, one that was carrying
Starting point is 01:38:54 male sex chromosomes and the other female sex chromosomes, came together at an early stage, and so what we have is a mosaic animal, where one side is genetically male and the other side is genetically female. Now, in a mammal, if that happened, the testis on the male side would masconize everything by using hormones. The clue that something else is going on in birds is that in this case, there's not been this blending. And when Art Arnold and others looked at the brains of genandromorphs, sure enough,
Starting point is 01:39:37 the sex differences where this region, HVC, for example, tends to be larger in males and females, in these animals, it was larger on one side of the body than on the other. So they were indeed, you know, split with this, this suggested that genital hormones were not in charge of sexual differentiation. And so what I wanted to do and never figured out quite how to do was to take a male brain and put it on a female body and vice versa. to ask what sexual differentiation will be like. Will the whole body listen to the brain and become male or will the gonads? It was a crazy experiment where if I could dissociate what the sex of the gonad was from what the sex of the brain was and what would happen. But it turned out,
Starting point is 01:40:30 you know, I didn't have the good hands that you would do, for example. I never learned how to do that experiment. But one resolution of it is one of the things we now know is going on in birds is that in some cases it's the brain itself that's making the hormone and is masculizing itself. So in birds, there's pretty good evidence that brain sexual differentiation happens because the genetic sex of the brain determines how much hormone, including testosterone and estrogen, is getting made locally, and that that then is driving sexual differentiation. And that's why you can have, you know, one side of the brain is male and the other side is females, and that just doesn't happen in mammals. That's the mechanism, once you start
Starting point is 01:41:14 using genital hormones to direct sexual differentiation, you can't end up with that sort of mosaicism, which is maybe too bad. I mean, there are carnival acts where supposedly one side of the body is male and the other side is female, and those have been around for quite a while, but that's a different thing. I'm going to give you two real world examples, real because I was told them, and I believe them. In anticipation of our conversation today, I ventured into some corners of the internet. I kind of wish I hadn't. But, you know, in gym culture, bodybuilding culture, there is a subset of people, I don't recommend it, that take synthetic androgens,
Starting point is 01:42:00 anabolic steroids of different kinds and in different combinations. And, again, I don't recommend people do this. but it's entirely different than hormone replacement therapy or something like that. Like experimentation with high dosages of different types of testosterone derivatives. And my interest in understanding a little bit of what some of the general observations are there is as a naturally occurring experiment with some thematic averages, which is geek speak for like if one person reports something, it means nothing. But if hundreds of people or thousands of people validate that experience, you think,
Starting point is 01:42:34 Well, it's kind of, you know, these aren't controlled studies, but nonetheless might be interesting. And those communities have long talked about how different forms of androgens have different effects on psychology. In particular, these days, you can find a lot of discussion in those communities of certain anabolic steroids, a trend blown in particular that causes aggression, but that is well known for, causing otherwise self-reporting as heterosexual males to start wanting to have sex essentially with males or females. This is an effect that seems reversible when they stop. It seems generally associated with a kind of a hypersexuality.
Starting point is 01:43:21 So that's an important variable, right? So there's all sorts of variables there. So that's one observation that makes me wonder if the adult brain is still plastic at the level of the hypothalamus to androgens later in life. Now, this is not to say that the many now millions of men who are taking testosterone replacement, it was very, very common doing that safely with doctors' support, etc., they're not trying to boost things into superphysiological range, but it's a naturally occurring experiment with very few controls and only anecdotal reports, but it suggests that the adult
Starting point is 01:44:00 hypothalamus is still androgen sensitive in ways that could drive pretty powerful changes in behavior and perception. And we know that is true because back in the previous century, Julian Davidson at Stanford actually in the physiology department there was among the first to do these double-blind placebo-controlled studies in men who had lost their testes for one reason or other, accident or cancer, things like that. And so double-blind means neither the man nor the physician who was interacting with him had any idea whether he was getting the placebo or the testosterone. And that's, of course, really important for coming up with conclusions. And they concluded that, in fact, the men who were getting testosterone definitely reported feeling better, feeling more
Starting point is 01:44:56 energetic, having a higher libido, and they definitely felt better overall. And Julian said, sort of the joke is that even though men were supposed to be blind to which treatment they were getting, they always knew. They always knew when they were getting the testosterone because they felt so much better. So we know if we're certain that testosterone does have effects on the adult brain in many of these cases, right, these are men's prostate cancer cases who were else. elderly yet and still, they still responded to that. Yeah, one thing I learned from your textbook was that, you know, this idea that testosterone
Starting point is 01:45:37 diminishes with age is largely true, but the rates are highly variable and that, you know, there are some individual points on the scatter plot whereby you'll see somebody in their 70s or 80s whose testosterone is very similar to someone in their 20s or 30s. Now, everyone nowadays talks about how testosterone rates are dropping. So it's a, you know, these are older studies. But it suggests that there's a tremendous amount of variation. We also know that absolute numbers don't necessarily dictate how people feel. In fact, the CEO of a very, very, very successful company, not a tech company, an entertainment company, came up to me once at a private party and said that his testosterone was down in the low 300.
Starting point is 01:46:21 So this is approaching the lower end of the reference range, but he feels great. And I said, if you're willing, like, what? variables are we talking about here? And he explained, you know, vigor, and he explained, you know, libido, and he explained, you know, general enthusiasm for life. And I said, well, I wouldn't change a thing in that case, right? I mean, he's a perfect case whereby low end of normal is not a problem. And who knows? Maybe had he taken more, he would have aromatized more to estrogen and he wouldn't have felt as good, for instance. No, I agree. I mean, if it ain't broke, you know, leave it alone. Yeah. I think it's something that doesn't get mentioned enough. But you also point out why human
Starting point is 01:46:56 are such lousy research subjects because there's so much variability going on. So what I can say is that for the decline in testosterone levels in men, first of all, it's so much more gradual compared to what happens to women at menopause, right? No comparison whatsoever. And there is an incredible amount of variation across subjects. And so once again, even though you can say statistically we know this is a trend, I can't make, you tell me someone's 71 years old just to pick on me, I can't predict what their testosterone levels are going to be like or not very well.
Starting point is 01:47:34 Another sociological observation from the internet. Everything on the internet is true. Certainly not everything on the internet is true. I know you were being sarcastic and certainly not everything on the internet is informative, but clusters and averages are interesting to me. There's a meme, which I find interesting vis-a-vis this type of conversation. whereby I think it was a martial artist, a MMA guy from either Russia or some eastern country, excuse me. The meme is it goes something like send two, three years, Dagestan and forget.
Starting point is 01:48:14 A guy is talking about how he wants his kid to be good at wrestling. And so he's going to send him to Dagestan where apparently the training is very intense. And the meme goes, send two, three years, Dagestan and forget. And he said, I'm going to send him there for a few weeks. and the guy goes, no, no, send two, three years, Dagestan and forget. And that meme, which is, it's not a cartoon. It's a guy actually speaking in that context has been, you can find extensive compilations of people showing kind of effeminate boys, dancing, doing kind of theater-type activities,
Starting point is 01:48:46 and then it transitions to send two their ears, Dagestan and forget. The idea being, returning to the beginning of our conversation, that there may be more plasticity early in life and that masculinization of behaviors stereotypically defined. Okay. I want to be very clear. The idea being that that's very plastic early in life. Okay. I think this is interesting and important to observe because when I was a kid, my mom, she still tells me the story,
Starting point is 01:49:20 but she told me this, verified this for many years. Okay. We had a pediatrician. This was in Northern California. This is just a mile or two away from Stanford School of Medicine. And my pediatrician said to her, you have a boy, Andrew, and there are three very important things in raising him. And these were his words. One, don't let him ride motorcycles. I agree. Two, don't let him drink soda. Too much sugar. Okay. Fair. And he said, three, don't let him do theater. The implication being that boys who do theater have a higher probability of becoming gay. Yeah. Now, that was, I was born in 1975, okay?
Starting point is 01:50:07 He gave this advice to every parent of a male. And I say that to kind of frame people's understanding of where we were versus where we are. and yet this meme is, I wouldn't say, rampant on the internet, but has a fair amount of support for it in the sense that I think there's still the general belief that certain activities can bias sexual orientation. And I just want to zoom out and ask, acknowledge the idea that the brain is plastic to androgens, behaviors impact androgens. So not trying to corral you into a given answer, but I think we've come a certain distance in this, but we're, we haven't really come that far. Well, and of course, there's no doubt that the younger brain is more plastic. I mean, there's no way around that.
Starting point is 01:50:59 But, you know, in terms of what one can do, there are limits. And in terms of sexual orientation, I can tell you, people look really hard for any social correlates. You know, you talked earlier about the dad that's missing, or even Freud talked about the overly coddling mother. and the dismissive father, that might make a boy more likely to be gay. And so people have looked for those sorts of quarrelists. The data just aren't there. I mean, it's really, which I think is interesting and kind of strange, because you'd think that if the social influence was that good,
Starting point is 01:51:39 that you'd find something. And so in terms of sexual orientation, I think the data are pretty weak. However, in terms of other expressions of male-like behavior, I mean, clearly culture and family has a say, right? I mean, they clearly make an influence, I mean, in terms of what boys they're supposed to do. I would say probably the only sex difference that will persist and that almost certainly is due to biological factors like testosterone is, you mentioned already rough and tumble play, across so many species, you know, you put a bunch of males. together and there'll be a lot more physical activity than if you put a bunch of females together. And an interesting thing happens if you put it in a mixed group and it doesn't matter whether it's monkeys or rats, the overall play will be intermediate. It's like the girls calm the boys down
Starting point is 01:52:32 and the boys ramp the girls up a little bit. And so that might be, you know, one that's going to be pretty hard to corral with social influences, but virtually every other expression. masculine behavior, of course, you know, culture and family make a difference. I don't know, you know, I'm going to suggest anyone send their child to. Augustine, two, three years and forget. Yes, thank you. Thank you for saying. The original statement, it was a real statement in a discussion, was aimed at something else. Yeah. It's been co-opted for this, for this. Like this is the form of, you know, intervention or whatever you want to call it. Okay, let's set the internet aside and talk about a different upbringing for a moment, which is yours.
Starting point is 01:53:19 Oh, as a scientist, you have a somewhat unusual trajectory in the science. So where were you born? In the Ozarks, in Springfield, Missouri. Oh, I was about to say, where are the Ozarks? I know where they are, but to orient our international audience. Southern Missouri and northern Arkansas. So it's famous because it's hill country. And so very hilly, very much like the Appalachians.
Starting point is 01:53:45 both in terrain and in culture, actually. So now I was born in the Ozarks in a working-class family. No one in my family had ever, well, known in my mother's generation, had finished high school, much less college. And, you know, I was always a little bit different because I was so much more interested in reading than all my cousins say all they remember about me when we were growing up
Starting point is 01:54:14 is I always had my nose in a book, right? that phrase. So, and I, as I get, I, I didn't choose that. I didn't choose to like reading, but I always did. And I always love school. And so, and I will say, I had a great family that was incredibly supportive of me doing whatever I wanted to, right? That that would, that would be fine. And as I look back, I realize, and I predict you'll find this too. The older I get, the more I realize how much luck matters and how many very fortunate things happen to me. Right. So the first question is I end up going to Yale College.
Starting point is 01:54:59 What? Working class. So my folks were blue-collar workers. I mean, for complicated reasons, I was raised by my grandparents. He was a construction worker, and she worked in a food processing plant. And so they once told me that maybe altogether they went to third grade, right? They got that far. But they were clearly smart and great people, and they were very supportive.
Starting point is 01:55:27 And so here's an incredibly lucky episode that happened to me. So when I was a junior in high school, I go to the Central High School Library, and I volunteered there after work to put away books. And the librarian tells me, oh, there's this book you might be interested in. And she shows me this really thick paperback made out by the college board. So this was the first year that the college board had put together this book showing all the colleges in the United States with little burbs about them. And she said, you might want to look at that. And I open it up.
Starting point is 01:56:04 And I see that for all the colleges, there's a paragraph about financial aid. So I read that entire book from front to back. except I only read the financial aid part, because at the time my grandfather passed away, and so my grandmother and our only income was Social Security, right? That was our livelihood. And so I read financial aid, everyone, and I get to the end. In this first edition, they were in alphabetical order, which makes no sense, but that's how it was. I get to the end, and the one for Yale College, it's like one of the shortest listings there,
Starting point is 01:56:40 And it says basically, we're committed to making sure everyone admitted will get the financial aid they need. This is me. This is where I need. You had to read the whole book just to get there. Well, the next entry was Yeshiva, which I thought, well, that's a strange name. But if they'd had that paragraph, believe me, I would have been applying there, which would have been fun too. And so I go to my counselor and I say, well, I'd never heard of Yale. I mean, I associated it with locks.
Starting point is 01:57:06 I'd heard of Harvard because of Kennedy, but, you know, nobody in my family. I go to my counselor, her name was Gene Walker, and she said, that's an Ivy League school. Huh? What does that mean? She tells me, and to her credit, she doesn't say that's stupid. You're never, you know, why would you be doing that? She says, you know what? You should apply for early admissions this year.
Starting point is 01:57:31 Early admission? I know. Okay. So I apply for early admission. I don't get it. So, okay. But I'll try again next year because that paragraph is really got it under my skin. And this is what I need.
Starting point is 01:57:39 So apply the next year. And this time, they ask me for an interview. And I'm to have an interview with Dr. John Ferguson. I'm to call up his office and arrange for an interview. And I'm sitting in French class with my friend Dale, and I'm telling him I'm supposed to make an appointment with Dr. John Ferguson. And the French teacher, who was one of my letter writers, Mrs. Fisher, she overhears this.
Starting point is 01:58:06 And she says, what on earth? why would you go see Dr. John Ferguson? Because she knew, but I didn't, he was an OBGYN. And I, you know, sort of sotivote. Well, you know, oh, well, I know John. He's an old family friend. I used to babysit him. And, you know, well, I'll be calling him.
Starting point is 01:58:26 So I'm sure, I don't remember the interview with the man, right? I mean, I don't remember a thing about it, but I'm sure he told him I was, you know, the greatest thing on earth. I'm sure he gave me a stronger recommendation as he possibly could. And so I got in, and they were true to their word. They send me this thick letter with all these financial aid. And they didn't expect my family to contribute anything. So it worked out.
Starting point is 01:58:58 And, you know, and what happened. I have mixed feelings about Yale because I've benefited. so much. I mean, and I'll credit myself with this. I went with the right attitude, right, which is they've made a mistake. Mrs. Fisher got me in, and I'm not going to screw this up. And indeed, you know, I, you know, Andy, I want to know everything. I want to know about art and literature and all the sciences. It was, I mean, I was hungry. And I, so, and I went with the attitude is, man, all these people are smarter than I am. And so I'm just, I'm just, I'm just, I'm just, I'm just going to soak it up. And at least half of what I learned at Yale, I learned from other students,
Starting point is 01:59:41 right? And the first night I'm on campus, you can see what happened. So first of all, I drive. Springfield to New Haven. It's a long drive, but, you know, that's how we go places. We drive. I get to New Haven, it's, where am I going to park this car? I can't, I just, of course, there'd be, you know, parking lots. Yeah. And so I find a place in downtown, a garage, and oh my God, this is going to cost me so much money to keep the car here. I got to take it back as soon as I can. And I go up to my dorm room in the old campus and I meet my three roommates. And I know how to be sociable.
Starting point is 02:00:18 So where did you go to high school? And two of them tell me they went to prep school. Huh? What's a prep school? They explain that too. And then they start talking about Phillips Andover versus Phillips Exeter. And the third guy, I won't mention the name, but his last name is one of, you know, generational wealth that every American has heard, right?
Starting point is 02:00:38 So it's like, okay, I'm not in the Ozarks anymore. And then they start, you know, smoking dope. And I've never seen that before, right? I've never been around people smoking marijuana before. And they assure me, oh, the campus cops, they'll look the other way. And I'm thinking, what, and that very summer in Green County, where I'm from, a judge had sentenced a young man for possession of marijuana, had given him a life sentence.
Starting point is 02:01:07 Whoa. For possession of weed? This is 1972, and this is the OSARCs, right? Not the same sort of place. So I'm thinking, well, maybe the campus cops would overlook you smoke a note, but I'm not going to give Yale any excuse to send me home. It was like a kid in a candy shop. And because I regarded everyone theirs,
Starting point is 02:01:27 they certainly knew more than I did, all of them. And they were probably smarter than I. It was like, I never felt the pressure to be the smartest person in the room. Okay, I'm not, I don't care. And I took as many classes as I could. And, you know, I always wanted to take six. You were supposed to take no more than five courses per term. And so I would always want to take six, and the dean wouldn't let me.
Starting point is 02:01:55 So I'd take five courses in a lab, which is like half a course, et cetera. And I'm just, you know, I'm not getting nays and everything, but I don't care, right? I didn't. So I'm having a great time. And that's when I learned about neuroscience. So first someone told me, oh, look at this course about comparative psychology. What's comparative psychology? It means comparing across species.
Starting point is 02:02:19 And, oh, I didn't know psychologists studied animal behavior. And then pretty soon I took a class, Linda Uphouse taught a physiological psychologist taught neuroscience, and I'm hooked, right? I mean, this is, I love this stuff. I mean, it's been an amazing arc to go from the Ozarks to Yale. I love that when you found yourself in an environment that offered a lot of opportunity, that you seized that opportunity. I think many people wouldn't have done the same, had they not had your background, but maybe even if they had. I mean, I think that when you find yourself in a place where there's tons to learn, And you throw yourself into that.
Starting point is 02:03:01 Only good things can come of that. I mean, you mentioned luck, but I think, you know, luck is, I wouldn't say, evenly distributed, but it has a habit of finding the prepared, as they say, right? I obviously didn't make that statement. And I love this theme of exploration. I mean, we, you know, I think of you as the hormones and sex behavior, your hormones and sexual orientation scientist, right? But I also remember, you know, it was 25 years ago that you always walked very quickly
Starting point is 02:03:37 and you always had an idea that you were excited about whenever I'd run into you. So I want to say you've really inspired my career to go after things that interested me and just really follow those trails. And also when it wasn't so clear what to do, to pick the, thing that at least was most exciting then and not worry about where that was going to lead next. You strike me as one of the least careerist people I've ever met. And I also acknowledge you've had a spectacular career and it's still going. I mean, your name is synonymous with hormones and behavior and hormones and sex behavior. You're being humble now, but it's absolutely true.
Starting point is 02:04:15 It didn't hurt that your last name was Breedlove, if I'm honest. But let's face it, that wasn't going to confer you like a real lasting advantage. So clearly, you've put in the work. I also really want to thank you for coming here today and teaching people what's known about these topics. And these are not easy topics to parse. The languaging has to be very specific. The reason it has to be specific is in one part political, sort of, but it's really about making sure that people understand what's true, what's not true, and what's not known yet so that they can form their own ideas. And I really admire the way that you're able to do that. And I also learned a ton today.
Starting point is 02:04:56 So, you know, I'm struck by a number of different things in this model of how we become who we are. And as someone who's raised kids successfully and now has grandkids. Yes, too. I knew your kids. So that's a trip to me. I haven't seen them in years. But they have kids. I think maybe you would just comment briefly on, you know, did you observe early sex differences in terms of behavior?
Starting point is 02:05:21 Was it striking? Did you do experiments on your kids? or did you opt not to? It was pretty amazing, really, now that you mention it, because Steve Clickman once told me that someone did a study where you asked people, how much do you attribute personality to nature and how much to nurture? And he said the only correlation that came out of it
Starting point is 02:05:43 was the more kids people had, the more they thought nature was important for determining. And you know that because if you have more than one, kid, they're not the same. And so in terms of sex differences, I'll tell you, so I have one daughter, Tessa, and she had two older brothers, et cetera. And, you know, my partner, Cindy Jordan, neuroscientist, too, and she almost never wore dresses, right? That would be our skirt. That was just, you know, not useful around the lab. And there was a period there where every day with Tassana, it was a struggle if we didn't put her in a dress, right?
Starting point is 02:06:27 She really wanted to wear. And as soon as she could walk, one of the things she liked to do was to put on her mother's various shoes, right, and walk around in them, cute, et cetera. I mean, she was so different from the beginning. Now, I'm not a biological determinist. I don't think biology is everything. I don't think, you know, prenatal things are everything.
Starting point is 02:06:52 There's no one cause of any human behavior, but it really struck me. Oh, and one of my boys could make a gun out of anything, right? You know, this is an era where we're trying not to. Even growing up in Berkeley. Oh, my, well, especially in Berkeley, because he wasn't going to find a toy gun, but by, by golly, he could make one. And he was also the kid that, you know, loved any toy with wheels on it, right? So it was, and you know, even among monkeys, right, Melissa Hines showed it first, even among monkeys, if you put in wheeled toys, it's the male monkeys that are much more interested in that than the females.
Starting point is 02:07:31 And the female monkeys are much more interested in the dolls, et cetera. So, yeah, you have more than one kid. I predict you're going to be amazed about how, you know, how different the kids are, even though you're the same family, right? they don't all come out the same. Once again, you've been a huge inspiration to me over the years, and I know that the listeners are greatly appreciative of everything you've taught, and we've got to get you back here.
Starting point is 02:07:58 Oh, also, you're writing a book about the biology of sexual orientation. I didn't know this. We actually don't really do book promos. That's not really our podcast, but when can we expect that book to hit the shells? Oh, you put me in such a tough spot. So I'm struggling with it. I've written six chapters, and I'm in, intending to 3rd B-11. My goal is, can I get this first draft done by this fall? And then, you know,
Starting point is 02:08:23 there's reviewing and things like that that happens. So I do, you know, knock on wood. I'm, I'm really hoping I'm going to finish this book. And if so, well, you know, I expect you, since you owe me so much, I expect you to buy a copy. Absolutely. I'll buy a copy. I'll read it, and I'll let the world know what I think about it. Dr. Mark Breedlove, thanks for coming here today. Come back again. It was a pleasure. I've had a great time. Thank you. Thank you for joining me for today's discussion with Dr. Mark Breedlove. To learn more about his work, please see the links in the show note captions.
Starting point is 02:08:54 If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review. And you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcasts
Starting point is 02:09:21 or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled Protocols, an Operating Manual for the Human Body. This is a book that I've been working on for more than five years and that's based on more than 30 years of research and experience.
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