Andrew Huberman interviews neuroscientist Dr. Marc Breedlove on how prenatal hormones shape sexual orientation
Andrew Huberman speaks with Dr. Marc Breedlove, professor of neuroscience at Michigan State University, about the biological underpinnings of sexual orientation.
Summary
Andrew Huberman interviews Dr. Marc Breedlove, a pioneering researcher in how hormones shape brain development and behavior. Breedlove presents evidence that prenatal testosterone exposure influences sexual orientation — supported by findings on digit length ratios, otoacoustic emissions, and brain structure differences between gay and straight individuals. He explains the "fraternal birth order effect," a well-replicated finding that each additional older brother increases the probability of a younger male being gay, and presents the maternal immunization hypothesis as the leading biological explanation. Breedlove also argues that sexual orientation involves not only attraction circuits but likely an aversive component — a finding supported by studies of gay rams — and that these two systems may be organized differently in males versus females.
Key Takeaways
FULL TRANSCRIPT
The biology of sexual orientation: why it is not a choice
Andrew Huberman: Dr. Marc Breedlove, welcome.
Dr. Marc Breedlove: Thank you. I'm delighted to be here. It's very exciting.
Andrew Huberman: It's been 25 years since we stood in the same physical space.
Dr. Marc Breedlove: I know. How can that be possible? I feel like I just saw you a few days ago.
Andrew Huberman: Well, you look great. You look the same. We can talk longevity protocols at the end.
Dr. Marc Breedlove: I'm trying to have a blonde look in my hair apparently.
Andrew Huberman: 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 — how and why people become who they are, and how hormones and genes play a role there. If you're willing, I'd like to jump from the high dive to the deep end first. Let's talk about this finger length ratios and sexual orientation study that you published. I landed on that paper and I want to talk about it because it's an incredibly interesting set of findings. Other people have done similar experiments, and there's a whole context about how hormones influence sexual orientation independent of behavior.
Dr. Marc Breedlove: We need to step back a little for context. In the year 2000, there were 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. Of course, I'm at Berkeley. I didn't have any truck with such notions at all. I've always been convinced that sexual orientation is not a choice. There's an exercise I do in class where I ask students to remember the first time they had a crush. It might have been someone on TV, might have been someone on a playground. I want you to think about how old you were at the time. My guess is it was before puberty.
Andrew Huberman: Yeah, I was six.
Dr. Marc Breedlove: And I hit puberty somewhere starting around 14. So it had nothing to do with puberty. It was this thing that happened. I'll share my experience. I'm about six or seven — I couldn't have been more than seven — and Marilyn Monroe is on TV. There's a closeup with that face and the mole. Afterwards I'm just so agitated. I know nothing about sex. I had a hard time going to sleep. Something about this was really agitating me and I didn't choose to have that reaction. My guess is that whatever sex you had your first crush on, that's the one you were going to be attracted to for the rest of your life.
Andrew Huberman: Yeah. It's been constant.
Dr. Marc Breedlove: So this idea that it was a choice always seemed so absurd to me. On the other hand, even though I've been doing animal research — giving hormones early in life and seeing what they did to the nervous system — every time I wrote an NIH grant, I said the effect of early hormones may be important for human behavior. But to tell you the truth, I never actually believed that. It just seemed to me that we are so sensitive to social influences, and we have this long stretch of time where our brains are still growing at a fetal rate until around 9 or 10 years of age. We're taking in so much information. And think of what a heterosexual world it is — all those Disney movies with Prince Charming, etc. 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 it was a choice, and it doesn't mean people would even be aware of what the social influence was.
My example is that I speak English. I'm hopelessly monolingual. I don't remember learning English and I certainly didn't choose to learn English, but I'm sure it's English because of social influences. That was where I stood on the question of sexual orientation until 1998 or 1999, when a fellow at the University of Texas, Dennis McFadden, came out with a paper that really made me think that prenatal testosterone might have an effect after all, despite my expectations. This was looking at otoacoustic emissions. Do you want to talk about those?
Andrew Huberman: These are people's ears making noise.
Dr. Marc Breedlove: 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 stops you from perceiving them long ago. But if Dennis puts you in a soundproof room and puts a very sensitive microphone in your ear, he'll hear these pops. I won't get into the acoustics of why that's a good thing — it helps you focus on the sounds you want to hear — but what Dennis knew is there's a sex difference in how many of these otoacoustic emissions are being made. Girls make more, and it's present at birth.
So Dennis comes out with this strange study — who would do such a thing? — where he proposes that since the sex difference is present at birth, it might reflect prenatal testosterone. He measured the otoacoustic emissions in straight men, gay men, straight women, and lesbians. He reports that compared to straight women, lesbians have fewer of these otoacoustic emissions. I couldn't think of any way to explain that except that lesbians might have been exposed to more prenatal testosterone than straight women before birth. And I don't know how to explain that except to say that maybe if you're exposed to prenatal testosterone before birth, you're more likely to be attracted to women when you grow up — which might explain why 95% of men are attracted to women, because they're all exposed to prenatal testosterone.
So this oddball study really gets me thinking that maybe there's something to that. But I'll forget it. I'm still working with my rats and prairie voles and Siberian hamsters. And then — I remember it so well — 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 9-year-old children. I've studied sex differences my whole adult life. How do I not know about this?
The digit ratio finding and what it reveals about prenatal testosterone
Dr. Marc Breedlove: It turns out that if you measure the length of the second digit — the pointer finger — and the length of the ring finger, you can do a simple ratio: divide the length of the second digit by the fourth digit, the so-called 2D:4D ratio. A guy named John Manning was reporting that there's a sex difference there — that ratio tends to be smaller in men than in women, and that it's present in children. A sex difference in the body that's present before puberty. I know enough about sexual differentiation of the body — it's almost certainly due to prenatal testosterone.
Andrew Huberman: Forgive me for interrupting, but people are probably looking at their hands right now. The 2D:4D thing can be a little confusing. Basically, in men the finger lengths are more different than they are in women. The typical heterosexual male pattern is that the pointer finger is shorter than the ring finger, whereas in women they tend to be more similar. Again, these are averages. And the difference between men and women is more pronounced on the right hand, as I recall.
Dr. Marc Breedlove: That's true too.
Andrew Huberman: Did I earn my authorship on the paper?
Dr. Marc Breedlove: Well, that and the fact that you persuaded so many people to answer our weird questions and let us xerox their hands. I'd never worked with humans before, but I'm sitting in the Bay Area — we have loads of gay people around. So I thought, let's try to do this. We started going out to street fairs. You were with us, going out to street fairs, asking people to fill out a questionnaire anonymously. I remember one of the organizers of a street fair said, "What should we do as an incentive to get people?" And they said, "Offer them scratcher tickets." So we asked people, "Will you please answer these very personal questions about who you have sex with, who you want to have sex with, and tell us everything about yourself anonymously, and we'll give you a $1 lottery scratcher ticket?" Andy, people will do anything for a $1 lottery scratcher ticket. It was the least expensive experiment I'd ever done in my life. Compared to any experiment with a rat — step one, buy a rat for $20 — it was nothing.
Andrew Huberman: It was very clear 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. If we needed to get a large cohort of gay women, we needed to go to the Solano Street Fair in Berkeley.
Dr. Marc Breedlove: And in Oakland. There was a brand new Oakland gay festival that got started. Oakland is a wonderful place to find lesbians. I thought the whole idea was kind of crazy, actually. I didn't think we'd come up with anything. And I insisted on measuring all the digits myself, which I did twice. Boring as hell.
Andrew Huberman: I recall when we were on what was like the third floor of Tolman Hall and you came running in. I was talking to my adviser, our good friend Zucker — one of the pioneers of circadian biology, who discovered the suprachiasmatic nucleus with Bob Moore and others. You came running in with a ruler and said, "Give me your hands." You grabbed my hands and measured them and said, "Well, that's weird — it's different on one hand than the other." Then you took the notes and measured his hands and left. I thought, what in the world is he doing? It turns out that was the early origins of the study.
Dr. Marc Breedlove: I measure these hands and I'm doing the math at the end of the day and lo and behold, I don't see any difference in the digit ratios of gay and straight men.
Andrew Huberman: Between gay and straight men. Which itself is interesting because it implies more or less equivalent amounts of prenatal testosterone exposure.
Dr. Marc Breedlove: Which I think is the case. And right now, 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. Since then there's been an evolution. The idea that gay men might have been underandrogenized always seemed strange to me. The really big sex differences in human behavior are not in math skills or verbal skills — those are tiny. The really big sex differences are in sexual attitudes. The biggest is that one sex is much more interested in multiple partners and younger partners than the other. One sex is much more interested in casual sex. One sex is much more interested in visual pornography. Those are huge sex differences. And in all those ways, gay men are totally masculine. So how would it work that they were underandrogenized and yet they have all these sex differences in sexual attitude? I think the difference between gay and straight men isn't in how much prenatal testosterone they got — it's in how their brains responded to the testosterone that they got.
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 at Penn State, and Ashlyn Swift-Gallant and I recently published what is like the third meta-analysis, and it's clear — so many people have seen it. As with Dennis's otoacoustic emissions, I don't know how to explain that unless, on average, lesbians 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?
What's really weird about it is the time lag. Your first crush — that mysterious, for me it was like a visitation, where did this come from? — that happened six years after you were out of the womb. 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 or ten years later when you have your first crush.
When we published that in 2000, it caused quite an uproar. I heard from a lot of strangers. Several people wrote who told me they were gay and were very positive and supportive. But I also got lots of emails from people saying, "I know you're lying. You're making this up to justify your gay lifestyle." It's like, well, I don't happen to be gay. We had a nice mix of orientations on the research team, but people were having a hard time with it.
To reassure your listeners who are looking at their hands: here's a joke I tell. I'm going to teach you right now how to look at someone's hands and guess their sexual orientation and be right 95% of the time. 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. While these average differences across groups are theoretically important because they do 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 digit ratio, because other things influence digit ratios too.
Andrew Huberman: Fascinating study. I got made fun of quite a lot, but I thought it was a blast. Some of the more outrageous things people asked me about the study — they all came from men — were things like, "If I cut off my index finger, will that raise my testosterone?"
Dr. Marc Breedlove: I would have said, well, let's try it and see.
Brain structure differences and the LeVay finding
Andrew Huberman: Am I correct in remembering that this sex difference in digit ratios is also present in mice?
Dr. Marc Breedlove: Yes. Wendy Brown and I did that first. I'd worked with mice and rats all my life but had never noticed the sex difference there. And a group looked at mice and did lots of genetic manipulations. It turns out that if you make the androgen receptor dysfunctional, the sex difference goes away. They showed that in mice, at least, there's more androgen receptor in the growing bones of the fourth digit than the second digit, and that's why the fourth digit grows a little bit more than the second digit.
Andrew Huberman: Beautiful. So androgens — things like testosterone, DHT, and other androgens — men and women both have them, other animals have them. Let's talk about effects of testosterone when we're in the womb. It's clearly having an organizing effect on the body plan. What is known about brain differences between men and women who identify as straight or gay?
Dr. Marc Breedlove: In terms of prenatally, we don't know. But the very famous study from Simon LeVay — who was already a highly respected neuroscientist with wonderful papers on the development of the visual system — got everyone's attention well before we did. He looked at a brain region in the hypothalamus, a specific region called the preoptic area or POA. He looked there and compared the size of the POA in the brains of gay men versus straight men. He looked in the preoptic area because in rats there's a very prominent sex dimorphism in a nucleus there — the sexually dimorphic nucleus of the preoptic area, or SDN-POA. Simon knew there was a huge sex difference there in rats. So he looked at the brains of gay and straight men and found a nucleus there — larger in men than in women — and what he found was that the nucleus in gay men was smaller than in straight men and in fact not significantly different from the size of the nucleus in women.
Andrew Huberman: So it wasn't hyper-male, like the finger length ratio was.
Dr. Marc Breedlove: No. In that case it indicated less exposure or less of a response to the androgen that was there. And Simon got even more of an uproar than I did. He published his paper in Science, and there were lots of people who were very skeptical, including some neuroscientists. But eventually another group replicated it.
Andrew Huberman: That's what I was going to ask. I recall that the two major critiques of the paper — one was fair, in my opinion. Some of the post-mortem samples were from people who had died of AIDS, and AIDS has some known neurodegenerative effects that may or may not have impacted the samples. And as I recall, he also got some pushback because he is openly gay and people accused him of agenda-driven science.
Dr. Marc Breedlove: Yes — that he was part of some conspiracy to force Americans to regard people with same-sex orientation as somehow okay. But a replication from an independent group that was very skeptical of it — William Byne — eventually saw it too. It took him a long time to get a sample big enough because, as treatment for HIV got better, the death rates started going down, so it took longer to gather the samples. But eventually he did, and even though he was skeptical, he saw it.
The question about AIDS — Simon was able to address that in that he also had some straight men who had AIDS and they weren't significantly different from other straight men. 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 — there's no non-invasive way to look at it. And he pointed out that he didn't know what the order of causation was. He doesn't know if those men had been born with a smaller SDN-POA and that's why they became gay, or did something else cause them to become gay and also cause the SDN-POA to get smaller.
For the public, the idea that a nucleus might change its size in adulthood might seem unlikely, but as neuroscientists we know that adult brains are changing all the time. Brad Cooke showed that there's a nucleus in the medial amygdala where there's a sex difference, but if you take away the testosterone in males, the sex difference goes away in just a matter of a few weeks.
Andrew Huberman: Unfortunately I remember the full name — it's the interstitial nucleus of the anterior hypothalamus. I'm not saying that to impress anyone. When you get to be 50, you wonder why your hippocampus remembers certain things that are basically totally useless.
Dr. Marc Breedlove: We waste so many synapses on totally useless crap. But that one's worth holding on to. So we don't know — it's a chicken-and-egg problem. We don't know if they were gay because they had a small INAH-3, or do they have a small INAH-3 because they're gay. What I always liked about Dennis's otoacoustic emissions is that it's pretty good evidence that the difference happened well before they had a sexual orientation. And nobody knew about this, so I wasn't worried that there were some little girls out there looking at their hands saying, "Gee, that looks kind of masculine. Maybe I should be a lesbian." Nobody knew this until your paper was published.
Andrew Huberman: Yes. As I recall, there was some schoolyard stuff of kids looking at each other's hands and trying to decide who was gay and who was straight.
Dr. Marc Breedlove: And every once in a while on the internet I'll see a little ad claiming to tell me something about my personality based on digit ratio length. Please — there's nothing to it. The fact that the group differences are there but you can't tell about differences between individuals is the hardest thing for scientists to communicate to the public at large.
Understanding group statistics versus individual prediction
Andrew Huberman: You have a really good way of explaining this to people. I'd love for you to give an example of how this plays out.
Dr. Marc Breedlove: Psychologists like to talk about measuring how big a difference is between two groups in terms of how many standard deviations apart the two means of the populations are. To give an example everyone knows: the sex difference in human height among adults. That's a huge sex difference — one we're all aware of. Those two averages are about two standard deviations apart. 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 — their height — and now you've got to guess what sex they are, you want to say everyone who is 5'5½" or taller is a man and everyone shorter is a woman. You'll be right about 80% of the time, which means you'll be wrong almost 20% of the time. There's some predictive power there, but it's far from perfect.
Well, this sex difference in digit ratios is half a standard deviation — a quarter of that. That means there's much more overlap. And we know that other things influence digit ratios too, not just prenatal testosterone. This is why there's no predictive value. 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.
Andrew Huberman: What about bisexuality — people who identify as attracted to both men and women?
Dr. Marc Breedlove: In those days, we didn't have enough people who identified as bisexual to have a reasonable sample. And it's interesting — that's something that's changed. If you do surveys now, especially among younger people, there are more people who report being bisexual than there were then. I don't really have anything to say about them. The one thing I will say is I'm sure that even among lesbians, there's more than one developmental pathway to become a lesbian or to become a gay man. I don't think there's just one thing.
Andrew Huberman: You do think, based on the data, that it's biological?
Dr. Marc Breedlove: Based on that data, I think testosterone has a say — prenatal testosterone. And it doesn't mean it's the whole package.
Congenital adrenal hyperplasia and androgen insensitivity syndrome
Andrew Huberman: There are conditions that are not uncommon where someone has a particularly stressful long phase of development where there's every reason to believe their androgens are impacted. And there's also every reason to believe there are stretches of development where androgens are increased. We know that certain types of activities and competition can increase androgen. So you can imagine there's some plasticity postnatally — before puberty, during puberty. You said something that even as a developmental neurobiologist I don't think I'd ever heard stated so clearly: that the rate of brain development from birth until age 12 is at least as fast as it was before we're born.
Dr. Marc Breedlove: The way to really bring that home is to compare human brain growth and chimpanzee brain growth. Up until birth, the rate at which brain size increases compared to body size is about the same in humans and chimps. 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 to ten years of age. People have pointed out that in a real sense, human children are fetuses that are outside learning a whole bunch of stuff from other people. That's the real distinctiveness of our species — we have this protracted childhood and really intense social learning, and a fetal rate of growth even though we're not in the fetus anymore.
Andrew Huberman: What's great about studying hormones and behavior is that sometimes you can control the hormone in animals. But the hard thing that people don't understand is that behavior can affect hormones. 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 had their testosterone levels go up a little, and the people whose candidate lost went down a little. You always have this cycle where the hormone alters the behavior and then the behavior alters the hormone.
Dr. Marc Breedlove: The only thing I know for sure is that the brain remains plastic all of our lives.
Andrew Huberman: That statement is a significant one. The hypothalamus remains plastic throughout our lives. I saw a paper just the other day that the neurons that control suppression of appetite — these POMC neurons in the arcuate nucleus — there's a population of them that are sort of undifferentiated and can become pro-hunger by expressing neuropeptide Y, and that there's a lot of late-stage plasticity. This may explain why people who reach a certain level of obesity may actually find that they're hungrier despite not needing food.
Dr. Marc Breedlove: I think both your statements are true. The neocortex is probably more plastic than the hypothalamus, but it's a matter of relativity. Every year when I went to the neuroscience meeting, the brain was more plastic than it was the year before, because there were more and more demonstrations. I think synapses can come and go just about anywhere. There might be less plasticity in the hypothalamus, surely, but that doesn't mean there's none.
Intersex conditions: CAH and androgen insensitivity syndrome
Andrew Huberman: Let's talk about what happens when the typical hormonal environment is disrupted. A graduate student my year, when you were my professor, Nikki Arpke — who was already famous for dog training dogs for the Beastmaster show — studied a species of mole in Tilden Park that could translocate its testes into ovaries and back again. 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. What is the deal with exposure to prenatal androgens and neither clearly male nor female genitalia?
Dr. Marc Breedlove: In most of those cases we're talking about congenital adrenal hyperplasia, also known as CAH. The congenital means it's present at birth. The adrenal hyperplasia refers to the fact that the adrenal glands are slightly larger. The reason they're slightly larger in this case is that these are individuals where the fetus itself is not able to make some of the adrenal steroids that are important for staying healthy. The brain detects this, drives the pituitary to tell the adrenal gland it needs more steroids. The adrenal gland gets the message and hypertrophies, but the machinery isn't there to make those steroids. So instead, the adrenal gland makes testosterone and other androgens. This can happen in either XX or XY individuals. In XX individuals, what that means is that prenatally her genitalia are being exposed to more testosterone than is typical. Under the influence of this extra testosterone, the clitoris may grow to be bigger than typical. In extreme cases, the phallus looks like a penis and the skin around that area that would normally form the labia may start to look like a scrotum — except there are no testes inside, because this is an XX individual.
These individuals are typically identified at birth, and there's an easy treatment: since they can't make adrenal steroids, you give them some, and for the rest of their lives they take adrenal steroids orally. That shuts off the hyperactive adrenal gland and its output of testosterone. This is what's known as an intersex phenotype. In the older literature, they were sometimes known as pseudohermaphrodites — with the idea being that a hermaphrodite is an individual that can function and reproduce either as a male or female, and supposedly they were "pseudo" because they can't do that since they have only ovaries. Being called a hermaphrodite, nobody liked that. A much more accurate description is to say that it's intersex — they have a phallus that's somewhere between a clitoris and a penis, and the skin around there is sort of like a scrotum and sort of like labia.
In the old days, once this got recognized, it was standard procedure to tell the parents, "This is an emergency. We need to do cosmetic surgery to make this little girl look like all the other little girls." 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. They were already taking care of the problem with the exogenous adrenal steroids. In some cases the tip of the clitoris was missing and these women grew up anorgasmic because they couldn't get the stimulation they normally would have had. These days, thanks to activists like Cheryl Chase and others who started getting pediatricians' attention, there's much more of a wait-and-see attitude. Wait until they're grown up and ask them then if they want to have surgery. My guess is most will say no, and I think that's been the pattern so far.
So these are females who were exposed to more testosterone than other females. Does that mean they're going to be attracted to women when they grow up? 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. What's interesting is the older they get, as you keep surveying them, the higher the percentage that report having a lesbian orientation.
Andrew Huberman: So it's possible that indicates that prenatal testosterone increases the odds of them being lesbians when they grow up. And you also wonder how many of them always had that same-sex attraction but were following the pathway society laid out for them, and then as they got older said, "No, I know who I'm attracted to."
Dr. Marc Breedlove: 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 — androgen insensitivity syndrome, sometimes abbreviated AIS. The gene for the androgen receptor that responds to testosterone and other androgens is on the X chromosome. It may sometimes be that a woman will have an X chromosome that has a copy of the androgen receptor gene that doesn't work. If she passes that X chromosome onto a son — in other words, that egg with an X chromosome that has a dysfunctional copy of the androgen receptor gene gets fertilized by a Y-bearing sperm — now we have an XY individual. The Y chromosome will mean that the indifferent gonad will develop as testes. The testes will secrete two hormones to guide sexual differentiation in the periphery. One of them being anti-Müllerian hormone, which is going to suppress the development of the Müllerian ducts — therefore no oviduct, no uterus will form. The testes will also release testosterone, which normally would masculinize the body. But in this case, because there's no functional androgen receptor to respond to it, the testosterone goes round and round but the body doesn't respond. The Wolffian ducts don't develop. The periphery looks like a typical female.
These individuals when they're born are often not identified — the doctor looks between the legs and says, "Congratulations, you have a girl." They grow up as girls undetected and come to a doctor's attention when puberty happens and all their classmates are having their period but she's not. She'll eventually go to an OB-GYN who will do a vaginal exam and notice that the vagina is relatively short, because the inner part of the vagina is normally derived from the Müllerian ducts — which in this woman never developed because of anti-Müllerian hormone. There'll be no cervix visible in the exam. If he takes blood plasma levels, he'll see that this very feminine-looking teenage girl has very high levels of testosterone.
Andrew Huberman: And presumably testes.
Dr. Marc Breedlove: Yes, there are testes in there, typically in the abdomen. They're releasing lots of testosterone because there's no negative feedback to tell the brain to stop sending signals to the testes. In these cases, you can ask: what's the sexual orientation of these women? The vast majority grow up to be straight. They are attracted to men, they're often very interested in having a family, and they're very much feminine, very straight women.
Andrew Huberman: But they're XY.
Dr. Marc Breedlove: But they're XY. So the question is — and unfortunately in terms of understanding whether prenatal testosterone alters our sexual orientation, these individuals aren't useful to us — because I 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. There's at least one woman with AIS who's self-identified and is a successful model. There's another woman who wrote a memoir that's quite good. And what's interesting about when there's no testosterone response is that they have very feminine faces and very feminine bodies.
The push-pull of attraction and aversion: gay rams and the preoptic area
Andrew Huberman: I'm realizing I'm drawing a model here whereby we've got different axes. For people who want to understand how hormones, sex, and sexual orientation fit together, it's very useful to think about: you've got chromosomes that drive our typical notions of male versus female, with important caveats where the body appears one way but it's XY. Then you've got choice of same versus other in terms of orientation, with a key role of prenatal testosterone. Maybe some cultural or other types of plasticity that might be biased more toward the female side. And then we have a bunch of different things about partner preference. At some point it almost seems like it departs from our sort of linear model — girls like boys, boys like girls, testosterone makes boys, estrogen makes girls. We've left that station a long time ago.
Dr. Marc Breedlove: Exactly. And at the same time we arrive at a place where we need better language to separate these axes, because it is very confusing for people. I think the lack of specificity in talking about orientation versus biological sex and these other aspects has led to a lot of conflict, actually.
Andrew Huberman: 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 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.
Dr. Marc Breedlove: It's been seen over and over. It's really one of the rock-solid findings in human sexuality. It was first noticed by Ray Blanchard at Toronto and has been seen in many populations all over the world. The way to emphasize the difference: if a baby boy is born today and he has no older brothers, his odds of being gay when he grows up is about 2%. Pretty low. But if he had one older brother, his odds go up by a third — to 2.6%. And if he has two older brothers, they go up a third again — 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.
Andrew Huberman: From the same mother, right?
Dr. Marc Breedlove: Right. So you get a big population of men. Here's a big population that have one older brother — how many are gay? A small number. The number that have two — still a small number, but more. When we did those surveys, we also asked people how many older brothers and sisters they had and how many younger brothers and sisters they had. In the general population, there are about 105 boys born for every 100 girls. 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.
Andrew Huberman: Is it a linear increase as you increase the number of older brothers?
Dr. Marc Breedlove: It is in fact a linear progression. Ray worked that out. It's hard to find men who had more than four or five older brothers, especially these days. But Ray went to the Kinsey surveys way back then — those interviews were incredibly thorough, and they have a record of how many siblings of each sex every one of those men had. And you can see it there too.
It's another one of these cases where I tell you this and you tell me, "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 you know somebody who has two older brothers and he's gay. Is that why he's gay? I really can't tell you. In fact, most men with two older brothers are straight. Ray Blanchard has done the statistics and their estimate is that of all the population of gay men, about one in seven are gay because their mother carried brothers before them. What I mean is those same men with the same genotype — if their mom hadn't had older brothers before them, they'd be straight today. Statistically speaking. But 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.
The maternal immunization hypothesis
Andrew Huberman: So the question becomes: for boys that had two or more older brothers but were not raised with those older brothers, does the effect hold?
Dr. Marc Breedlove: It's a beautiful hypothesis, and that's the first thing you think — maybe the younger brother got bullied or beat up by his older brothers, and maybe the older brother somehow inhibited the younger brother from developing in a fully masculine fashion. But it turns out Tony Bogaert started looking at these data and asking: what about stepbrothers? Do older stepbrothers make any difference in the odds of sexual orientation? And the 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 them. So it does not seem to be socially mediated.
In fact, Ray Blanchard and Tony Bogaert have come up with a very plausible hypothesis called the maternal immunization hypothesis. 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. 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. At that point, the mother's immune system is going to see these male-specific antigens that it's never seen before. It's going to regard them as invaders and start making antibodies to them. So their hypothesis is that each time a woman delivers another son, her immune system is going to generate more of these antibodies. If she has a subsequent son, antibodies cross the placenta just fine — in fact, the placenta very actively sends antibodies across to protect the young. That would mean her antibodies are going into this third son and somehow altering the development of their brain.
The strong evidence they found in favor of this is that in women who have sons where this pattern looks like it might have happened, they have higher levels than control mothers of antibodies to a male-specific antigen — quite specifically an antigen to a protein called neuroligin 4Y.
Andrew Huberman: Neuroligins are important for synapse formation.
Dr. Marc Breedlove: Exactly. There are several copies of neuroligin — not unusual in humans — and this one, neuroligin 4, has one copy on the X chromosome and one on the Y chromosome, and they're slightly different. The fact that these mothers are making antibodies to this male-specific antigen, and that in their particular family subsequent sons are more likely to be gay — you can imagine that's what's going on. Her immune system has perturbed the development of that subsequent son enough that when they grow up, they're more likely to be gay.
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, and it's the mother's body that is somehow 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 I mentioned before: there are lots of different developmental pathways to end up being gay or to end up being straight. 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.
Andrew Huberman: The result is so cool because once again it spits in the face of these reflexive assumptions. You could imagine — and I probably grew up hearing — "Oh, he was raised around a lot of girls" or "he had an older sister or three" or "dad left the house." There was this idea of lack of male influence. But in terms of the stereotype, when you look at the biology, it's exactly the opposite.
Dr. Marc Breedlove: Ray's looked at that very carefully. Older sisters don't matter, and neither do younger sisters. And younger brothers don't matter either — no matter how many younger brothers you have, that doesn't change your odds of being gay when you grow up. That's why I say it's got to be the mother's body that is remembering. It doesn't seem to be socially mediated. It is nature having its say.
Gay rams, the preoptic area, and the aversive component of sexual orientation
Andrew Huberman: I know of one example in sheep, of all things.
Dr. Marc Breedlove: Yes. Chuck Rosselli out at Oregon studied this very carefully. 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. Chuck did 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 put a ram in with them. Most rams will mount the females. He puts in these rams that prefer males. If there's a variety of sheep's backsides in front of him, he'll mount males — including sometimes having intromission through the anus all the way to ejaculation — and he never mounts a female. In some cases, he'll put the gay ram where there's a dozen females and he might be in that paddock for twelve hours and never mount a single female.
Andrew Huberman: Highly unusual for male rams.
Dr. Marc Breedlove: And it's a small percentage of the population. I don't know how to explain that. You would think that at some point, well, there's nothing else to do in here, I'll mount one of these. And they never do. I don't know how you can explain that except that there's some aversive component — that these gay rams do care about the sex of their partner, and for them there's some aversive component to mating with a female. Chuck told me not too long ago there's a company that has identified these gay rams and decided that instead of sending them off to slaughter, they're going to harvest their wool and sell them as clothing. You can buy wool clothing that came from gay rams and know that you saved them from the slaughterhouse.
Andrew Huberman: There's no response that's appropriate to that statement.
Dr. Marc Breedlove: And apparently they're out of stock. So it's been a big success.
Andrew Huberman: I left off the kicker.
Dr. Marc Breedlove: Chuck eventually dissected the preoptic areas of these various rams and found a difference between the preoptic area of gay rams and straight rams — a difference in how they process testosterone in exactly that part of the brain, the preoptic area, where Simon LeVay saw a difference between gay and straight men. So there may be something about the hypothalamus, the preoptic area, that has something to do with orientation, if we're talking about an organism complicated enough to have an orientation — including sheep.
Andrew Huberman: 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. Across neuroscience we see this push-pull — a flexor muscle like the bicep, when it flexes, the tricep relaxes. When the tricep flexes, the bicep relaxes. These antagonistic relationships. You see this in the hunger circuit. Hunger and feeling full are like a push-pull, a seesaw. And you said something that I was not aware of but that makes perfect sense: 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. But this idea that there's also an aversive aspect to it — I think this is important and something I have not heard discussed before.
I think sociologically it has relevance because there's this not uncommon theme whereby many people — not all — find the concept of mating with the same sex aversive. That has shaped a lot of the landscape around this. I'm not trying to get political. 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 we're never going to get where we want to go as a society until we really understand the biology and how to work with it.
Dr. Marc Breedlove: 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 — here's this difference in the brain. He doesn't know when the difference happened in their preoptic areas, but it seems to correlate with this idea that maybe these gay rams are not interested in having sex with females. It's aversive to them. There's no other way I can explain how they choose never once to mount a female.
Andrew Huberman: The acknowledgment of an aversive pathway for sexual partner choice is as important as the acknowledgment of biological correlates of homosexuality. Because if this sort of conversation is ever to advance past the sort of "okay, what's okay to say now" — trust in science disappears. I really believe that. The problem is that people leverage fragments of what they hear in order to make arguments in favor of whatever stance they have. 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.
Dr. Marc Breedlove: And this makes you old-fashioned, because that's not the world. Our world seems to be hurtling towards a world of snippets.
Andrew Huberman: People will notice that we have not used the word gender. We're talking about biological sex and sex the act. We're talking about male versus female partner choice, a desire for one or the other, and an aversion to one or the other. The aversion piece is an important theme. So here's a hypothesis: it may be that in male humans there's a pathway or a molecule that serves as an aversive circuit — peptides, neurons, etc. — that suppresses sexual desire for other men and activates some level of disgust. And that in women there is no such pathway. There's either desire for women or desire for men. 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 sex differences in who people are willing to have sex with.
Dr. Marc Breedlove: Your hypothesis fits the data. It is true that in the early '90s, when the first gay characters were on television — the real first Real World, and subsequent characters started to dismantle some of the stereotypes of the effeminate gay man — what you saw was that heterosexual women seemed to be more generally accepting of gay men before heterosexual men embraced that as typical.
Andrew Huberman: That's my impression too. And then there's a societal shift and it sort of becomes like — I spend some time on X, formerly known as Twitter, and there are some gay political accounts and you just kind of notice that people are comfortable with it. Men and women seem to be comfortable with that. That's very different from what you would have observed in the late '80s or early '90s. I think these are important biological phenomena — this notion of an aversive pathway. You could imagine where societal standards or community standards or household standards might amplify or reduce the expression of these things.
Dr. Marc Breedlove: I'm sure they do. Cultures can amplify or reduce that component. The question is to what extent, and I don't think we know.
Testosterone, adult brain plasticity, and behavior
Andrew Huberman: What are some of the other effects in human studies of behavior impacting hormones that come to mind for you?
Dr. Marc Breedlove: For testosterone, I think the big ones have been competition between males. And there's the stress response, but that's a whole other thing.
Andrew Huberman: What about sex behavior itself?
Dr. Marc Breedlove: In animals, at least, we know that 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. We know that plasticity is there and we know 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 — kind of preparing them for maybe something coming down the pike. So we know that's a reciprocal relationship when the animal's in charge of the hormone.
Andrew Huberman: For the longest time, thanks to your textbooks — and by the way, Mark has authored some of the most important textbooks on hormones and behavior and developmental neurobiology — the textbook version of male versus female sexual behavior has been a story about females having a circuit that goes from brain to body to control 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. Your lab and others has really parsed this right down to the details. And yet people have sex that way but also other ways. How should we make sense of these biological circuits that define stereotyped motor behavior?
Dr. Marc Breedlove: You're getting at exactly what every textbook author has to deal with. We know so much more about the circuits involved in the motor behaviors because they're relatively easy to trace and manipulate and study. We know lots about the motor patterns in animals. We know a lot less about the motivational patterns in animals, which in human sexual behavior is in many ways the whole show. We don't really have good animal models of libido. This was brought home to me many years ago when I was on a segment of 60 Minutes. Leslie Stahl was there in our lab. The producers had called me up and said, "Can you show us a way that early testosterone exposure changes behavior permanently?" I said, "Sure, 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. They came three months later, and I showed them those motor patterns. 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. Leslie immediately dubbed him Romeo. She hates rats, by the way, so she was very brave.
I drop a female on top of Romeo and he starts mounting and she shows the lordosis posture. Beautiful and easy. Then I said, "Now I'm going to drop a male, a control male in." And Romeo, of course — you don't know unless you try — he mounts several times and the male rat acts like nothing's going on. 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 — the sort that the control male never showed. So here this neonatally castrated male is showing very female-like patterns.
Miss Stahl kept asking me, "Would you say this is a gay rat?" I'm definitely in a tough spot because I don't think my rats have an orientation. Romeo happily mounted any rat I threw in the cage. What I would say is that 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. 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 lordosis to whoever mounts her. And my male rat will mount any rat he comes across just in case he gets a lordosis out of them.
Andrew Huberman: Good on you for not getting corralled into giving a particular answer. Romeo is an interesting case because I thought you were going to say that Romeo was willing to mate with a female if she was receptive, but wouldn't if she wasn't. I was surprised that he would try to mount a male as well. That doesn't align with my experience of male human behavior.
Dr. Marc Breedlove: Certainly not. That's right. This is the thing that's distinctive about humans — we're not actually that particular about what particular motor behaviors we engage in, and we're overwhelmingly interested in who our partner is. That is an overriding concern that I don't think my rats have. Here's the anthropologist from Mars, and I tell you: here's whoever's the sexiest man alive this year. This is an interesting discussion altogether because people have been lining up images of these people and claiming there's some effeminate drift. But the point being that it's not fixed.
Andrew Huberman: Yes. Well, whoever — let's say it's George Clooney. Here's someone that half the planet believes is an ideal sexual partner, but the other half of the planet finds him totally unacceptable, even if the behaviors they engaged in would be pretty much the same. In terms of positions and who's doing what to whose genitalia, for most people it isn't that there has to be one particular act. Their overwhelming concern is the gender or the sex of that other person. It's hard to have an animal model of that.
Dr. Marc Breedlove: I actually do know of one example in sheep, if you want to talk about this.
Janandromoprhs in birds and the head transplant experiment
Andrew Huberman: Did you ever do the head transplantation experiment on the finches?
Dr. Marc Breedlove: No, I never did. But I think we should talk about the backdrop of this. Male birds of certain species sing. Female birds don't.
Andrew Huberman: So you wanted to embryonically put a female head on a male body, a male finch head on a female body, and swap head-bodies of these embryos. Tell us the experiment.
Dr. Marc Breedlove: I'm certainly looking like the mad scientist. But let me say — crazier things have been done with US tax dollars, like mice that glow in 215 different fluorescent colors to identify different cell types. This experiment has a purpose to get at a principle that can't be understood any other way.
In fact, people do those sorts of transplants in birds. A very famous neuroscientist from France, Nicole Luran, did experiments where she would open up chick embryos and quail embryos and scoop out part of the nervous system from one and implant it in the other. She had a way of telling the cells apart under a microscope. Plus, when they grew up, you'd have this white Leghorn chicken with a streak of brown feathers right where she had done the transplant — derived from the quail. So it is possible to do those sorts of swaps.
There was a question about sexual differentiation of the brain in birds. 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. Sometimes you'll see in the news someone will find a gynandromorph in birds.
Andrew Huberman: Half female, half male. And when it happens in cardinals, for example, it's like the animal's been split down the middle.
Dr. Marc Breedlove: Yes. One side is the bright red of a male with a crest, etc., and the other side isn't. Our best understanding of what happened there is this is a case where two embryos — one carrying male sex chromosomes and the other female sex chromosomes — came together at an early stage. 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 testes on the male side would masculinize everything by using hormones. The clue that something else is going on in birds is that in this case, there's been no such blending. When Art Arnold and others looked at the brains of gynandromorphs, sure enough, the sex differences — where this region HVC, for example, tends to be larger in males than females — in these animals it was larger on one side of the body than on the other. So they were indeed split.
This suggested that gonadal hormones were not in charge of sexual differentiation. 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 to dissociate what the sex of the gonad was from what the sex of the brain was. But it turned out 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 masculinizing itself. 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 then drives sexual differentiation. That's why you can have one side of the brain be male and the other side female. That just doesn't happen in mammals. Once you start using gonadal hormones to direct sexual differentiation, you can end up with that sort of mosaicism.
Testosterone, behavior, and adult plasticity: real-world observations
Andrew Huberman: Going to give you two real-world examples. In anticipation of our conversation today, I ventured into some corners of the internet I kind of wish I hadn't. In gym culture, bodybuilding culture, there is a subset of people — I don't recommend it — that take synthetic androgens, anabolic steroids of different kinds and in different combinations. My interest in understanding some of the general observations there is as a naturally occurring experiment with some thematic averages — which is geek speak for: if one person reports something it means nothing, but if hundreds or thousands of people validate that experience, you think, well, this might be interesting. Those communities have long talked about how different forms of androgens have different effects on psychology. In particular, certain anabolic steroids — trenbolone in particular — are well known for causing otherwise self-reporting 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 hypersexuality. 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.
Dr. Marc Breedlove: We know that is true because Julian Davidson at Stanford — in the physiology department there — was among the first to do double-blind placebo-controlled studies in men who had lost their testes for one reason or another, accident or cancer. Double-blind means neither the man nor the physician interacting with him had any idea whether he was getting the placebo or the testosterone. They concluded that the men who were getting testosterone definitely reported feeling better, feeling more energetic, having a higher libido, and feeling better overall. Julian said the joke is that even though the 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 for certain that testosterone does have effects on the adult brain in many of these cases. These were men — prostate cancer cases who were elderly — and still they responded.
Andrew Huberman: One thing I learned from your textbook was that this idea that testosterone diminishes with age is largely true, but the rates are highly variable. 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. We also know that absolute numbers don't necessarily dictate how people feel. In fact, the CEO of a very successful company — not a tech company, an entertainment company — came up to me once at a private party and said his testosterone was down in the low 300s, approaching the lower end of the reference range, but he feels great. I said, "If you're willing, what variables are we talking about?" And he explained vigor, libido, general enthusiasm for life. And I said, "Well, I wouldn't change a thing in that case." Who knows — maybe had he taken more, he would have aromatized more to estrogen and he wouldn't have felt as good.
Dr. Marc Breedlove: I agree. If it ain't broke, leave it alone. And you also point out why humans are such lousy research subjects — there's so much variability going on. 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 — there's no comparison whatsoever. And there is an incredible amount of variation across subjects. Once again, even though you can say statistically we know this is a trend, I can't predict what a 71-year-old's testosterone levels are going to be like.
Rough-and-tumble play, social influences, and the limits of plasticity
Andrew Huberman: There's a meme on the internet — I know you were being sarcastic that everything on the internet is true — whereby a martial artist, an MMA guy from Russia or some eastern country, is talking about how he wants his kid to be good at wrestling and is going to send him to Dagestan where apparently the training is very intense. The meme goes "send two, three years Dagestan and forget." That meme has been co-opted by people showing what they describe as effeminate boys doing theater-type activities, and then transitioning to the idea of sending them to Dagestan — the idea being that there may be more plasticity early in life and that masculinization of behaviors, stereotypically defined, is very plastic early in life.
When I was a kid, my mom still tells me this story. We had a pediatrician in Northern California, just a mile or two away from Stanford School of Medicine. He said to her, "You have a boy, and there are three very important things in raising him." One: don't let him ride motorcycles. Two: don't let him drink soda — too much sugar. And three: don't let him do theater. The implication being that boys who do theater have a higher probability of becoming gay. That was advice he gave to every parent of a male. I say that to frame people's understanding of where we were versus where we are. And yet this meme has a fair amount of support in the sense that there's still the general belief that certain activities can bias sexual orientation. The brain is plastic to androgens. Behaviors impact androgens. Not trying to corral you into a given answer, but I think we've come a certain distance in this, but we haven't really come that far.
Dr. Marc Breedlove: There's no doubt that the younger brain is more plastic. But in terms of what one can do, there are limits. And in terms of sexual orientation, people have looked really hard for any social correlates. You talked earlier about the absent dad, or even Freud talked about the overly coddling mother and the dismissive father that might make a boy more likely to be gay. People have looked for those sorts of correlates. The data just aren't there. Which I think is interesting and kind of strange, because you'd think that if the social influence was that good, you'd find something.
In terms of sexual orientation, I think the data are pretty weak for social influence. However, in terms of other expressions of male-like behavior, clearly culture and family have a say. In terms of what boys are 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 rough-and-tumble play — across so many species. 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. An interesting thing happens if you put them 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 and the boys ramp the girls up a little bit. That might be one that's going to be pretty hard to corral with social influences. But virtually every other expression of masculine behavior — of course culture and family make a difference.
Marc Breedlove's background: from the Ozarks to Yale
Andrew Huberman: Let's talk about a different upbringing for a moment — yours. As a scientist, you have a somewhat unusual trajectory into science. Where were you born?
Dr. Marc Breedlove: In the Ozarks, in Springfield, Missouri.
Andrew Huberman: Southern Missouri and northern Arkansas — hill country, very much like the Appalachians both in terrain and in culture.
Dr. Marc Breedlove: I was born in the Ozarks in a working-class family. No one in my family had ever — well, no one in my mother's generation had finished high school, much less college. I was always a little bit different because I was so much more interested in reading than all my cousins. All they remember about me when we were growing up is I always had my nose in a book. I didn't choose to like reading, but I always did. I always loved school. I had a great family that was incredibly supportive of me doing whatever I wanted to. The older I get, the more I realize how much luck matters and how many very fortunate things happened to me.
I end up going to Yale College. My folks were blue-collar workers. For complicated reasons, I was raised by my grandparents. He was a construction worker and she worked in a food processing plant. They once told me that altogether they went to third grade. But they were clearly smart and great people and very supportive.
Here's an incredibly lucky episode that happened to me. When I was a junior in high school, I go to the Central High School library and volunteered there after school to put away books. The librarian tells me, "Oh, there's this book you might be interested in." She shows me this really thick paperback put together by the College Board — the first year the College Board had put together a book showing all the colleges in the United States with little blurbs about them. She said, "You might want to look at that." I open it up 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, but I only read the financial aid part, because at the time my grandfather had passed away and my grandmother and I — our only income was Social Security. I get to the end, and in this first edition they were in alphabetical order. I get to the end and the one for Yale College is like one of the shortest listings there, and it says basically: we're committed to making sure everyone admitted will get the financial aid they need. This is me. This is what I need.
Andrew Huberman: You had to read the whole book just to get there.
Dr. Marc Breedlove: Well, the next entry was Yeshiva, which I thought, well, that's a strange name. If they'd had that paragraph, I believe me, I would have been applying there too. So I go to my counselor — her name was Jean Walker — and I say, well, I'd never heard of Yale. I associated it with locks. I'd heard of Harvard because of Kennedy, but nobody in my family talked about these things. She says, "That's an Ivy League school." I ask what that means. She tells me, and to her credit she doesn't say, "That's stupid, why would you be doing that?" She says, "You know what? You should apply for early admissions this year." So I apply for early admission. I don't get it. But I'll try again next year because that paragraph has really gotten under my skin. I apply the next year and this time they ask me for an interview with Dr. John Ferguson. I'm to call up his office and arrange for an interview.
I'm sitting in French class with my friend Dale, telling him I'm supposed to make an appointment with Dr. John Ferguson. The French teacher — one of my letter writers, Mrs. Fischer — overhears this and says, "What on earth? Why would you go see Dr. John Ferguson?" Because she knew, but I didn't — he was an OB-GYN. She said, "Well, I know John. He's an old family friend. I used to babysit him. I'll be calling him." I'm sure he gave me as strong a recommendation as he possibly could. And so I got in. They were true to their word — they sent me this thick letter with all this financial aid, and they didn't expect my family to contribute anything.
I have mixed feelings about Yale because I benefited so much. I went with the right attitude, which is: they've made a mistake, Mrs. Fischer got me in, and I'm not going to screw this up. I wanted to know everything — about art and literature and all the sciences. I went with the attitude that all these people are smarter than I am, so I'm just going to soak it up. At least half of what I learned at Yale I learned from other students.
The first night I'm on campus — first of all, I drive from Springfield to New Haven. I get to New Haven and I can't find parking. I find a garage downtown and think, oh my god, this is going to cost me so much money. I go up to my dorm room in the old campus and meet my three roommates. Where'd you go to high school? Two of them tell me they went to prep school. What's a prep school? They explain it, 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 those generational wealth names that every American has heard. So it's like, okay, I'm not in the Ozarks anymore. Then they start smoking dope and I've never seen that before. They assure me the campus cops will look the other way. And I'm thinking — that very summer in Greene County, where I'm from, a judge had sentenced a young man for possession of marijuana to a life sentence.
Andrew Huberman: Possession of weed.
Dr. Marc Breedlove: This is 1972 and this is the Ozarks. Not the same sort of place. So I'm thinking, well, maybe the campus cops would overlook you smoking, but I'm not going to give Yale any excuse to send me home. It was like a kid in a candy shop. Because I regarded everyone there as knowing more than I did, I never felt the pressure to be the smartest person in the room. I took as many classes as I could. I always wanted to take six — you were supposed to take no more than five courses per term. The dean wouldn't let me, so I'd take five courses and a lab. I'm not getting A's in everything, but I don't care. I'm having a great time.
That's when I learned about neuroscience. Someone told me, "Oh, look at this course about comparative psychology." What's comparative psychology? It means comparing across species. I didn't know psychologists studied animal behavior. Then I took a class — Linda Uphouse, a physiological psychologist, taught neuroscience — and I'm hooked. I love this stuff. It's been an amazing arc to go from the Ozarks to Yale.
Andrew Huberman: I love that when you found yourself in an environment that offered a lot of opportunity, you seized that opportunity. I think of you as the hormones and sex behavior, hormones and sexual orientation scientist. But I also remember — it was 25 years ago — that you always walked very quickly and always had an idea you were excited about whenever I'd run into you. You've really inspired my career to go after things that interested me and follow those trails. You strike me as one of the least careerist people I've ever met. And I acknowledge you've had a spectacular career and it's still going. Your name is synonymous with hormones and behavior. It didn't hurt that your last name was Breedlove, if I'm honest, but 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. These are not easy topics to parse. The languaging has to be very specific — not just for political reasons, but really to make 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. I admire the way you're able to do that. And I learned a ton today.
I'm struck by a number of different things in this model of how we become who we are. As someone who's raised kids successfully and now has grandkids — I knew your kids, so that's a trip to me — maybe you would just comment briefly on whether you observed early sex differences in terms of behavior. Did you do experiments on your kids or did you opt not to?
Dr. Marc Breedlove: It was pretty amazing. Steve Glickman once told me that someone did a study where you ask people how much they attribute personality to nature and how much to nurture, and the only correlation that came out of it was the more kids people had, the more they thought nature was important. Because if you have more than one kid, they're not the same.
In terms of sex differences, I'll tell you. I have one daughter, Tessa, and my partner Cindy Jordan — she's a neuroscientist too — almost never wore dresses. That was just not useful around the lab. And there was a period where every day with Tessa, it was a struggle if we didn't put her in a dress. She really wanted to wear one. As soon as she could walk, one of the things she liked to do was put on her mother's various shoes and walk around in them. 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 prenatal things are everything. There's no one cause of any human behavior. But it really struck me. And one of my boys could make a gun out of anything — this is an era where we're trying not to, especially in Berkeley. He wasn't going to find a toy gun, but by golly, he could make one. And he was also the kid that loved any toy with wheels on it. Even among monkeys, Melissa Hines showed it first — if you put in wheeled toys, it's the male monkeys that are much more interested in that than the females. And the female monkeys are much more interested in the dolls. You have more than one kid, I predict you're going to be amazed about how different the kids are, even though you're the same family. They don't all come out the same.
Andrew Huberman: 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. We've got to get you back here. Also, you're writing a book about the biology of sexual orientation. When can we expect that book to hit the shelves?
Dr. Marc Breedlove: Oh, you put me in such a tough spot. I'm struggling with it. I've written six chapters and I'm intending there to be eleven. My goal is to get this first draft done by this fall, and then there's reviewing and things like that. I'm really hoping I'm going to finish this book. And if so, since you owe me so much, I expect you to buy a copy.
Andrew Huberman: Absolutely. I'll buy a copy, I'll read it, and I'll let the world know what I think about it. Dr. Marc Breedlove, thanks for coming here today. Come back again.
Dr. Marc Breedlove: It was a pleasure. I've had a great time.