TED Radio Hour - Listen Again: The Biology Of Sex

Episode Date: April 15, 2022

Original broadcast date: May 8, 2020. Many of us were taught biological sex is a question of female or male, XX or XY... but it's far more complicated. This hour, TED speakers explore what determines our sex. Guests on the show include artist Emily Quinn, journalist Molly Webster, neuroscientist Lisa Mosconi, and structural biologist Karissa Sanbonmatsu.See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

Hey everyone, it's Manusche, and something quietly changed for U.S. citizens this month. If you're applying for a passport, you can now choose the gender X instead of male or female. The X stands for unspecified or other gender identity. And it's just the latest sign of how society's approach to gender and sex has rapidly changed. Our understanding of the science of male and female has rapidly changed, too. As we explain in this week's episode, The Biology of Sex. This show originally aired in May 2020, but it is so densely packed with information. It is definitely worth listening twice.

I know I had to. So enjoy it again or for the first time. And thank you so much for being here. This is the TED Radio Hour. Each week, groundbreaking TED Talks. Our job now is to dream big. delivered at TED conferences. To bring about the future we want to see around the world.

To understand who we are. From those talks, we bring you speakers and ideas that will surprise you. You just don't know what you're going to find. Challenge you. We truly have to ask ourselves, like, why is it noteworthy? And even change you. I literally feel like I'm a different person. Yes.

Do you feel that way? Ideas worth spreading. From TED and NPR. I'm Anoush Zamorodi. On the show today, the biology of sex. And just a quick note, we're talking about our physiology, our physical bodies. So if you're a kid, it might be good to listen to this one with a grown-up. Some of the things we talk about could be a little confusing.

Okay, before we get into everything, can you just describe where you grew up? Because it was a pretty traditional and conservative kind of environment, right? Yeah, I grew up in Salt Lake City, Utah. I wasn't Mormon, but I grew up surrounded by the Mormon culture, I guess. This is artist and activist Emily Quinn. In that culture, women are expected to get married, have kids. It feels like you're groomed from a very early age for motherhood, and they equate motherhood to women.

womanhood and vice versa. And I kind of grew up surrounded by this idea that if I wasn't able to do that, then I wasn't really worth much as a woman. And so when you were still pretty young, you went to the doctor. And what did they tell you? Yeah. So we went to a gynecologist when I was 10. And if you've ever been to a gynecologist, you know it's not a fun experience. For a 10-year-old, it was very, very, very traumatic because that was right when the maturation program was happening at school. Is that like sex ed? Sort of, yeah. I mean, it's like fifth grade puberty training almost.

Like the girls go in one room, the boys go in the other. Like I remember we went into the half of the auditorium and watched a video about getting your period and all that stuff. And so my mom was just kind of like, and remember, like this isn't. going to happen for you. So it was, I already knew at that point. Can we talk about what the doctors told you? You were told that you had a disorder. Is that correct? Yes. Yeah, I've told I have a disorder of sex development. I'm pretty sure it was angiogen sensitivity syndrome. That was all the language that they used. The term intersex I didn't hear for a long time. Emily Quinn continues her story on the TED stage. I have a vagina.

She thought you should know. That might not come as a surprise to some of you. I look like a woman, dressed like one, I guess. The thing is, I also have balls. And it does take a lot of nerve to come up here and talk to you about my genitalia. Just a little.

But I'm not talking about bravery or courage. I mean literally, I have balls. Right here. Right where a lot of people. you have ovaries? I'm not male or female. I'm intersex. Most people assume that you're biologically either a man or a woman, but it's actually a lot more complex than that. There's so many ways somebody could be intersex, and in my case it means I was born with XY chromosomes, which you probably know is male chromosomes, and I was born with a vagina and balls inside my body. I don't respond to testosterone,

During puberty, I grew breasts, but I never got acne or body hair, body oil. You can be jealous of that. But even though I don't actually have a uterus, I was born without one, so I don't menstruate. I can't have biological children. We put people in boxes based on their genitalia. Genitals don't actually tell you anything, yet we define ourselves by them. In this society, we love putting people into boxes and labeling each other. It gives us a sense of belonging and teaches us kind of how to interact with one another.

But there's one really big problem. Biological sex is not black or white. It's on a spectrum. These days, we talk a lot more about gender identity, like using the pronoun they instead of he or she. And there's a growing acceptance that people express. their gender on a spectrum, feminine, masculine, non-binary, and more. But we have a lot to learn about the biology of sex, what were assigned at birth. Because despite what most of us were taught in health class, there's more to it than just

female or male, XX or XY. And so on the show today, the science and spectrum of biological sex, how our DNA expresses itself in a variety of ways. It's more complicated than we often is. assume. And as Emily Quinn says, what you see on the outside can have little to do with what's happening on the inside. To be clear, like, not only do you look like any other girl, but, like, you're very feminine and, like, super pretty. Sorry, I hope that's not. Buy me dinner first. But you are, like, you present as, like, an extremely feminine woman.

And so for, I think there's something about it. being you explaining this to people that is particularly surprising because you're like, yes, but I have X, Y, chromosome. And you're like, I grew up thinking that was a man. Right. It's confusing. No, it is. It feels like we haven't learned how biology really works.

Right. And that's the truth of it is that it's so much more complex. So when I talk about sex and biological sex, I specifically talk about seven different. different areas, and people will talk about this in all various ways. I talk about the seven areas being your chromosomes, your gonads, like testes or ovaries. Sometimes you can have a mixture of the two, or you can just have one or neither. Then there are your internal organs like your uterus or fallopian tubes or whatever, your external genitalia, your hormone production, your hormone response, and then your secondary sex characteristics, which is like breast development, wider hips, facial hair, body hair, et cetera, muscles, everything that we kind of categorize as male or female that are all secondary.

So, like, my body started out as male, and then it, like, went down a different path, if that makes sense. But somebody's body could go down a different path at any one of those seven areas. And as a kid, because I grew up in Utah and I had to be a woman, like I was so scared of anyone finding out that I was quote unquote secretly a boy. I mean, like you said, I definitely started dressing more girly and femininely. And that was more from my own shame and need to fit in and not be discovered or let my secret out or whatever. The sex and gender binary are both so ingrained in our society

that we never stop to think about it until somebody comes along to make you question it. And if you're thinking that I'm the exception, an anomaly, an outlier, intersex people represent around 2% of the population.

That's the same percentage as genetic redheads. We're not new, we're rare, we're just invisible. We've existed throughout every culture and history, yet we never talk about it. In fact, a lot of people might not know that they're intersex.

A friend of mine found out last year in his 50s. The Executive Director of Interact, which is the leading organization for intersex human rights here in the U.S., she found out she was intersex at age 41. Her doctors found out when she was 15, but they didn't tell her. They lied and said that she had cancer because that seemed like an easier option

than finding out she wasn't fully a woman. This kind of thing happens a lot where intersex people are lied to or kept in the dark about our bodies. It's rare to me an intersex person that hasn't been operated on. And oftentimes, these surgeries are done to improve intersex kids' lives, but they usually end up doing the opposite,

causing more harm, both physical and emotional. I'm not saying that doctors are bad. It's just that we live in a society that causes some doctors to fix those of us who don't fit their definition of normal. We're not problems that need to be fixed. We just live in a society that needs to be enlightened. Emily, if you could go back in time, what do you wish had been different about the way you were treated as an intersex person? What I really wanted was somebody saying, hey, like, this is going to be okay. Like, that's not a big deal and it's not like that life-changing because that's the thing.

If I hadn't had all these societal experiences, it wouldn't be that big of a deal. Even with small things, like learning at an early age, so most people are boys or girls, but some people are in between. And kind of learning that would have been. life-changing because it would have meant I belonged somewhere. And as a kid, I never really belonged anywhere because I didn't belong with the girls and I didn't belong with the boys because that's all we knew. And so if I had somewhere that I fit in and that I belonged and I didn't just constantly feel like an imposter, that would have been huge. You know, I was actually there when you gave your TED talk. And I have to say, your tone right now is just so different.

Like you were so sassy and funny and you were like, yeah, I'm balzy. And like, you know, you can't help but laugh because it's what you're talking about. And there's this moment in the TED Talk. I remember it so vividly, your voice broke and you looked so surprised. And you even said, I think, I didn't think I was going to get emotional. And I feel like at that moment, I remember thinking like, oh, there's a crack there. And I hear it in your voice now. And I wonder if that's what's happening as you're exploring that crack.

And that must, if that's the case, that sounds like a lot of work. You're making me cry. I'm sorry. No, it's okay. Yeah, I think that's the issue is that when you take humans out of the equation, especially in a medical capacity, it leaves a lot of trauma, unfortunately. It's been within the last month that I've started really trying to dive, deeper into that trauma and I didn't realize how much I held in my body. Yeah, it's a lot.

But I also think, like you said, like the fact that we can sit here and laugh about it, that's massive because for so long I couldn't talk to anyone about it. And I'm aware of how much, like, how awful that was and how much that hurt. And I don't feel that hurt anymore, which is really good. And I think that's part of what has come from being able to laugh and talk and be very open is, you know, I was able to go from not telling anyone to shouting it on the rooftops. And, you know, like it was just so freeing. Emily Quinn, you can find her full talk at TED.

On the show today, ideas on the biology of sex. I'm Manoosh Zamoroti, and you're listening to The TED Radio Hour from NPR. It's the TED Radio Hour from NPR. I'm Manushe Zomerode. And on the show today, the biology of sex, because it's more complicated than just female or male, X, X, or X, Y. One of the things that I was super surprised about was finding out the spectrum of biological sex. You know, we say X is female, Y is male, or X, X, X, X, is female and X, Y is male. I mean, that's how we cheer someone if they're having a boy or if they're having a girl when they announce that they're pregnant.

People love those gender reveal parties. Yeah. Yeah. This is radio journalist Molly Webster. And what I came to find out was that you can be a whole compilation of X's and Y's. So you can be X, X, X, Y. You can be XY Y. You can be X-O. Hmm.

I mean, it just goes on. And I was like, things that I thought were just like immutable biological truths can be changed in some way. A lot of these kinds of questions came up for Molly while she was working on a series called gonads. Episode three, I'm Molly Webster. For the show, Radio Lab. You're listening to Radio Lab. When they found these chromosomes, it was clear that if you had X, Two X chromosomes, you would develop as a female.

A girl. Anatomic female. And if you had a Y chromosome. So your X, Y. You would develop as an anatomic male. That's right. A boy. That was the thinking.

So you see, Roger and Susan are born a girl. That is not wrong, but I think what I became very fascinated in was all the ways in which there's so much more to the story than just egg and sperm maker. like in connection to X and Y. Which then raised one really big question. Why do we have such a simplistic view of biological sex? It's a specific way of thinking about things from a certain moment in history that we are potentially starting to rethink. I think it's helpful to see sort of the history of how we understand sex in a longer time frame. And that takes us to the turn of the 20th century when scientists first discovered that the last,

that 23rd pair of chromosomes decides our sex. For me, the true story of X and Y starts with their name. Here's Molly Webster on the TED stage, along with some voices of scientists she taped while reporting on her series. So within years of being discovered, these two little chromosomes had acquired more than 10 different names. There was diplosome and heterochromosome and idiochromosome, and most of the names had to do with their structure, their shape, their size.

And then there was sex chromosome, which they had been given because of the fact that we had started seeing that the X would go with the females and the Y would often go with the males. But scientists were like, do we really want to call them sex chromosomes? And science historian Sarah Richardson is the one who told me this story. For three decades, scientists were like, you should not call them the sex chromosomes. The X and Y have many functions, and, you know, you wouldn't assume that a single chromosome controls a single trait. Imagine calling one chromosome the urogenital chromosome or the liver chromosome. They ended up getting sex chromosome. But in the 100-year history since we settled on that name,

you can see it starts to get a little complicated. X and Y, their discovery and our understanding of them are actually super foundational and crucial to the field of genetics. But even when that field was just very, very nascent, there was even a hesitation at that moment to assign a total identification of sex to these chromosomes. And there were warnings of, like, sex is a really, really powerful word that has all these connotations and traits associated with it, culturally, socially,

and attaching that to something biological can be pretty sticky. Yeah, and it's something we conflate a lot with gender, too, right? Yeah. You know, there's gender, which is how we identify, and that's a personal identification on top of our physiology. And so when I'm talking about sex, I'm talking really about our biology and our physiology. So I'm feeling a rising sense of foreboding here based on what you mentioned earlier about why the scientists were concerned about naming it the sex chromosomes. Like what were the implications of calling them sex chromosomes? Yeah, there have been a number sort of at a scientific level and at a social and cultural level.

So in my talk, I end up just stepping through a couple of moments that just jumped out at me while I was doing. research is like, oh, there's an implication. There's an implication. And so my first stop was discovering X, Y, Y, which it becomes known as something called the super male. Wait, a super male? Yeah. So the theory goes, if at that time or even today, if we're really believing that Y is male and X is female, then what quickly follows behind that belief is the idea that traits that we associate with males and traits that we associate with females could in some way be coded in our DNA. Huh. So a few years after they realized that you can be XYY, researchers go to a prison in Scotland and they do genetic analysis of a bunch of the male prisoners.

And they find a number of people who are XYY. And according to Sarah, they just rushed to publish a theory. suggesting that this extra Y chromosome could explain criminality in some men. Yeah. So the logic goes like this. By this point, we're thinking, why is male? We think male is aggressive. So why must be aggression? If you got an extra Y, you must be crazy. And like, we went nuts with this theory. We called it the super male. They started scanning more prisoners, serial killers, boys, and in all seriousness, there was actually a suggestion that we consider aborting XYY fetuses. So in 1980, this theory pretty much toppled for a number of reasons. One, there had been

this really large study that basically showed there was no connection between Y and violence. And then there was one other thing. Going back and looking at those original findings and that high-security psychiatric institution, they had also found a high number of individuals with an extra X chromosome. So these are X, X, Y, as opposed to X, Y. Now, they never claimed that the individuals with an extra X chromosome were super females. They never investigated whether they had higher rates of violence. Seems like kind of an oversight. I don't know. But I think it's interesting because what you see is if you start looking at these chromosomes through the lens of sex,

what naturally falls in place behind is we look at them through the lens of gender and the traits that we associate with gender. And while we don't believe in super males today, there is a very similar conversation that's still happening around inherent violence in boys and biology. I think, you know, on the one hand, we're looking for reasons for behavior.

Back to your example of the criminals, you know, wouldn't it be nice to be like, oh, it's not their fault. They were born with this. It switches on a kind of behavior. And I feel like that would almost make people feel better in some ways. And so I think all of us in the world are trying to understand, like, what assumptions that am I making these days based on old-fashioned ways of thinking. about what sex and gender are?

It's an interesting question. It's so complicated because I think, you know, for me, it's calling one part of the body sex that is potentially dangerous. Like, yes, there's definite ways that biology influence behavior. And yes, I have two chromosomes that are linked tightly in ways to sex, but biology is so complicated that to say that it's X and Y or testosterone and estrogen or, you know, whether you have ovaries or testes, that that specific thing is what's causing behavior. It's like that thing is one thing of a thousand, I'd even say a million things that are happening in the

body that's trickling up and causing behavior. And so it's like recognizing how complex it is that it's never going to be one thing, you know? But one thing that we all have to have is the X, right? Yeah, so one thing that I had never actually thought about until I talked to this scientist, Melissa Wilson, in Arizona, is the fact that every human being on the planet has an X. Like I had so, and again, you know, sometimes I wonder, maybe this is all just in Molly's brain.

But I think that other parts of the world and other people I've talked to think these same things. Yeah, it's so tightly associated X with femaleness and Y with mailness. I'd overlook the fact that everybody has an X and that you can't survive without an X. You have to have one. And so suddenly it was like, whoa, whoa, whoa, whoa, whoa. Everyone has to have an X. Like, what is that X doing? It can't just be sex, right?

Of the almost 1,100 genes on the X chromosome, how many do you think have to do with sex and reproduction? Just like, get a number in your head. 4%. That means 96% of the rest of that chromosome is doing something that has nothing to do with your gonads. And I guess as all of these sort of some of them, social stories, some of them scientific stories,

some of these facts started to add up. I just thought, like, why are we calling these the sex chromosomes? Or if we are, like maybe we all like that. name, should we just allow ourselves to think about them a little more broadly? Because if we do, like, what insights would we gain as people, as scientists? And I just wondered if it wasn't a moment to rethink the biology of X and Y, and at the very least, to remember, like, the footnotes of history, which is that the dude who came up with the phrase sex chromosome actually was like, Hey, everyone, just remember, this is just, and I quote, a form of shorthand.

We should not take it literally. It's fascinating. I mean, and it makes me think that we're in the midst as a society to having a nuanced understanding of gender. But where are we, do you think, in terms of having a nuanced sense of sex, biological sex? I think we're still many steps away. You can see that society is in a very different place than I think than what's happening in some labs right now. And part of that has to do with a trickle up effect. Like it takes a long time for stuff to get into textbooks and to be taught in different ways.

It also has to do with, you know, teachers don't have endless time to like get to all the nuance. And a lot of the science is new. And if it's not new, it takes a long time to take hold. And so it feels like an important moment just to start planting seeds in people's minds. Like, let's be open to this because even at the very beginning of the science, they were open to this. That's Molly Webster. She's a radio journalist on the show Radio Lab. Her series is called GONADS.

And you can listen to her full talk at ted.com. On the show today, the biology of sex. And just as Molly Webster said, Our chromosomes carry our genes in DNA molecules. And our DNA tells our bodies how to express themselves physically, whether we have ovaries or testes, whether we have a vagina or penis. But what about our brains? There are many theories on how women's brains differ from men's brains. That's neuroscientist Lisa Moscone on the TED stage.

I've been looking at brains for 20 years. Pink and blue, Barbie and Lego. Those are all inventions that have not. nothing to do with the way our brains are built. That said, women's brains differ from men's brains in some respects. Lisa studies the connections between neuroscience and biological sex, specifically when it comes to women's health. And hormones are a big part of that.

A lot of people working in my field, like in the brain field, to not really look at hormones that much. We don't think about the reproductive organs as something they could potentially affect. the brain and OBGYNs are not equally prepared perhaps to talk about the brain. Hormones allow the brain and the reproductive organs to talk to each other, and that conversation is crucial. So from a scientific perspective, from biological perspective, DNA really dictates what kind of hormones your body is producing.

So still during the prenatal phase, when you're basically an embryo developing, these chromosomes really dictate what kind of hormones are circulating in your bloodstream and then inside your brains. So if you have an XX to start with, your brain is going to develop in such a way that optimizes for estrogens. And that starts very early.

It's almost three months into gestation where the baby brain is born and then it's going to grow more and more. but already then there are growth factors that really promote brain development and development of the body of the child and immediately start populating the baby brain with estrogen receptors. Whereas if you have an XY, then the Y chromosome contains genes that will make your body produce androgens like testosterone. And that means that your brain is going to optimize 4.5. androgen receptors. So from the very moment you're born, you're going to have a brain that is really

loaded with estrogen and estrogen receptors or with androgens androgen receptors. So structurally, these brains are a little bit different or biochemically. These brains are a little bit different from the moment you're born. Most people think of the brain as some kind of black box isolated from the rest of the body. But in reality, our brains are in constant interaction with the of us. These interactions are mediated by our hormones, and we know the hormones differ. Men have more testosterone, women have more estrogens. So the brain is connected to the reproductive systems via a network that is called the neuroendocrine system. Our brains and ovaries are part of the neuroendocrine system. As part of the system,

the brain talks to the ovaries and the ovaries talk back to the brain every day of our lives as women. So the health of the ovaries is linked to the health of the brain and the other way around. At the same time, hormones like estrogen are not only involved in reproduction, but also in brain function. And estrogen in particular, or estradiol, is really key for energy production in the brain. I think it's interesting to know how hormones actually work. They're a little bit like a key that needs to open specific locks. Yeah. And these locks are called receptors. So, for example, in the female brain, there are very specific parts of our brains that are very dense with receptors.

And that's where the hormones go. They bind to the receptors. They kind of turn them on. And that generates a million different things. Like brain energy is powered. You have more immunity. There's more resilience against disease. You have more plasticity.

You have more growth. And all these hormones together are. responsible for the menstrual cycle in women, and they're connected to the ovaries, the gonadal system. And the men, obviously, they're connected to the testes. So these systems are really important, and these different structures are connected to each other via the hormones, the flow back and forth every day of our lives. So it's not just reproduction. There are so many things that need to happen inside the brain that are really facilitated by these hormones. More from Lisa Mascone on how our brains develop differently.

We're talking about the biology of sex. I'm Manoosh Zamoroti, and you're listening to the TED Radio Hour from NPR. Stay with us. It's the TED Radio Hour from NPR. I'm Manushe Zomerodi. And on the show today, the biology of sex. We were just talking to neuroscientist Lisa Mascone about the differences between the average male and average female brain.

When it comes to our brains being either male or female, is there actually a range when it comes to the brain and hormones? Because we've been hearing on this episode about XXY or XYY people. And earlier we spoke to Emily Quinn, who shared her personal story about how she is intersex, that she is XY. But actually her body doesn't respond to testosterone. own only estrogen, which from your description seems like it would be a response to X, X, X, chromosomes, but she has X, Y chromosomes. So I guess I'm wondering, like, is there a spectrum?

Oh, for sure. For sure. There's a lot of overlap between different brains and different people. I think what we see as scientists is that on average, like the average male brain is somewhat bigger than the average female brain. Isn't that just a stereotype? No, it's true. Male brains with more androgens, like testosterone, are generally bigger. Okay. But then there's everything else in between. So, yes, it's never black and white.

A lot of people ask me, if I give you a brain scan and you just look at the brain scan, can you tell me if that brain belongs to a man or a woman? I was like, no, of course not. Yeah, no, you cannot. You cannot do that. But then how do you know the difference? When's the moment when you're like, oh, yes, this is female? Or, oh, yes, this is a male brain?

In my experience, the most defining feature is the change over time starting in our late 40s. So instead of looking at the anatomy of the brain or the volumes or the size of the brain, what really changes is the functionality of the brain. So women's brains tend to show decline. in brain energy levels around menopause, whereas these declines are not seen in men of the same age. So if you give me a brain scan and you don't tell me who the scan belongs to, but I can see brain energy levels, let's say, in a person's life, 45, 48,

women are much more likely than men to have lower metabolic activity. In their brains? In their brains. Yes, in their brains. Okay. So as a woman barreling towards her late 40s, that gives me great pause because essentially what you're saying is that a man my age is pretty much going to have the same brain his whole lifetime. But as a woman, my brain is going to go through a change because my body responds to hormones differently, correct? Yes.

Yes. And it's not just menopause. think we think of aging as a linear phenomenon, but it's not really linear. So both men and women go through something called a transition stage. Puberty is a really big one linked to an explosion of hormonal power. Men just all of a sudden have a ton of testosterone. Women have an enormous amount of estrogens. And that has really been shown to change. the structure, the function, and the connectivity of the brain in both teenage boys and girls, right, in adolescence. And what's interesting is that this remodeling leads to a lot of synapses to be discarded.

And synapses are the point of connection between different neurons. And that has been interpreted as an optimization. So the brain is getting rid of all the neurons that it doesn't really need. cleaning house, okay? Yes, exactly. It's like, you're doing a nice cleaning. You're like, okay, at this point, you know how to tie your shoes, right? So I don't need this noodles anymore. You can do it by yourself. But then there are two things that happen to women and not to men that also impact our brains in a big way. Pregnancy, being a really important one, the brain goes through remodeling after the baby is born. Wow. It's very similar. Yeah, it's

very similar to what happens during puberty. So the brain seems to be actually getting rid of a bunch of nutrients and synapses. That is true. I'm laughing because it felt like that. I felt like my, I felt like I had a different head on my shoulders after I had a baby. Yeah, for good and bad, you know. And, you know, it really, I really felt like they'd swapped out, like, my thinking process.

But what you're saying is, like, that is kind of what happened. The hormones. gave my brain a big old shower, and I emerged as kind of a little bit of a different person, I guess. Yes, absolutely. And so many women tell me the same, but that's an optimization. From an evolutionary perspective, that's a plus. And then women going through another transitional stage, which is menopause. And what we have shown is that these changes, these symptoms, do not start in the ovaries, as many people,

think. They start in the brain. So how much of this is based on genetics? Because it kind of sounds like overall, our genes dictate how our brains will respond to our hormones. Like, is that the right way to look at it? It's in part genetic, but also in big part is really whatever happens after you're born. So all your experiences, the way you live your life, your medical health, all these things really combine to dictate, number one, the health of your hormones, number two, the health of your brains, and number three, how these two different systems really work with each other. Our brains are different. They're not better or worse. They're just different. And they're not,

this difference is just about pink and blue or what kind of toys we like or what kind of jobs we want to have. It's really, it's not just gender role, it's a sort of health. That's neuroscientist Lisa Moscone. Her latest book is The XX Brain. You can see her talk at TED.com. On the show today, the biology of sex. And so far, we have talked about chromosomes, gonads, hormones, brains. But there is so much we don't know about how we end up the sex that we do.

And we may not find out for a long time. Looking more and more into the research, you know, there is so many open, questions, so we're trying to understand now, but there's no smoking guns yet at all. This is structural biologist Karissa Sanban Matsu. She works at Los Alamos National Laboratory, and she's asking some of those questions that may change how we see biological sex in the future. But before turning to biology, Karissa studied lots of things. I was really inspired by Star Wars really in the beginning, and I wanted to go into astrophysics, so I did that in college. I started again.

getting into chaos theory, complex systems, and nonlinear theory. And then I did laser fusion. But then when I became a principal investigator at Los Alamos, my heart was really with biology. And so I was obsessed with the origin of life. And the reason why Carissa went from studying the stars to studying what determines biological sex is a personal one. Here's Carissa on the TED stage.

When people learn that I'm a woman who happens to be transgender, They always ask, how do you know you're a woman? Well, as a scientist, I'm searching for a biological basis of gender. I want to understand what makes me, me. Carissa was assigned the male gender at birth. About a decade ago, she transitioned to female, but her new life was sometimes painful. I knew I was a woman on the inside, and I wore women's clothes on the outside.

But everyone saw me as a man. in a dress. I felt like no matter how many things I try, no one would ever really see me as a woman. In science, your credibility is everything, and people were snickering in the hallways, giving me stares, looks of disgust, afraid to be near me. I remember my first big talk after a transition. It was in Italy. I'd given prestigious talks before, but this one, I was terrified. I looked out into the audience and the whispers started, the stairs, the smirks, the chuckles.

To this day, I still have social anxiety around my experience eight years ago. I lost hope. Well, don't worry, I've had therapy, so I'm okay. I'm okay now. But I felt enough is enough. I'm a scientist. I have a doctorate in astrophysics. I published in the top journals in wave particle interaction,

space physics, nucleic acid biochemistry. I've actually been trained to get to the bottom of things. So from there, I started delving into, you know, why am I transgender and so forth? And I think that if we can show people that it's something legitimate, then maybe people will take this a lot more seriously. And so if I understand correctly, that is when you actually decided to research this as your career. And you started to delve into what happens to our job. DNA, right? Like epigenetics, that that could be the thing that makes us male or female or maybe cisgender or transgender. Yeah. And it turned out to be this really exciting field that was kind of

exploding just as we were working on it. And it was right at the time I was going through the transition as well. And so basically in epigenetics, it's interesting in that, you know, a lot of things people wonder, is it nature or is it nurture? Were you born this way, or is it a choice? And epigenetics is this new field that sort of sits in between where basically the environment reprograms genes, and those switches stay permanently. So it sort of sits right in between nature and nurture.

So we're all born with our DNA, but our environment can change the way our DNA is expressed. So just like Carissa said, epigenetics reprograms our genes, deciding the path our DNA takes. Yeah, and I think path is really the operative word here that you hit on. And so there's something called Waddington's landscape. Okay, Waddington's landscape. I love this.

It's kind of a well-known analogy about epigenetics. So imagine your cells are marbles rolling down a hill, developing, deciding what to eventually turn into. And as you're going down, you always have to make that decision as you go down and down and down. And as it's rolling down at any point, it's going to go left or right. And scientists like Carissa are trying to understand how epigenetics might change the path our cells take, as our bodies develop in female or male ways in utero. And for transgender studies, there are a lot of reports that sometimes it's passed down through the generations and sometimes it's not. So there are a lot of features of it that really just scream, it must be epigenetics.

So that's kind of where we're looking now. Yeah, because actually I heard this because I had a conversation with a friend whose daughter is transitioning. And correct me if I'm wrong, but she said that people are talking about this idea that the fetus can possibly develop in different ways in utero. Like the genitals develop one way in the first trimester, but then in the second or the third trimester, the brain development leads toward a different sex. Is that right? Yeah, so that's a current working model that many people subscribe to in that the genitals differentiate one way, but the brain differentiates the other way. And we think that the obvious mechanism for that to happen is through epigenetics, because epigenetics is deeply involved in almost all the decisions that are made during development. And most of the epigenetic changes are caused by hormones that would basically silence a gene or a whole set of genes.

at the critical moment that would change the course of the development of that baby. Okay, as Carissa said, this is a working model to explain a possible biological reason for gender dysphoria. But applying epigenetics to sex and gender, this is pretty new. It's kind of controversial. And scientists are really far from connecting the dots on it. I'd hope for one day to have some kind of blood test maybe or something with the epigenetic marks. But, you know, we're a long way out from. anything like that, I think.

And so your piece of this puzzle is studying how the DNA expresses itself, and then that is used by scientists studying fetal development, right? Exactly, exactly. To truly understand DNA decision-making, we need to see the process in atomic detail. Even the most powerful microscopes can't see this. What if we try to simulate these on a computer? We need a million computers to do that.

That's exactly what we have at Los Alamos Labs. A million computers connected in a giant warehouse. So here we're showing the DNA making up an entire gene folded into very specific shapes of knots. For the first time, my team has simulated an entire gene of DNA, the largest biomolecular simulation performed to date. For the first time, we're beginning to understand the unsolved problem how hormones trigger the formation of these knots.

Okay, so I want to make sure I understand this right. You are showing how the DNA folds and makes these knots, and those folds and knots are deciding the path of the DNA, like basically showing epigenetics in real time. Yeah, that's right. And again, like, this is just one piece. Like, you are one scientist among many scientists trying to connect the dots in this super vast and complicated field of biological sex,

and then how that connects to genesis. and you're each just trying to figure out one step, right? Yeah, so we're down at the atomistic molecular cellular level. Everyone needs to work on this because it's so complex. And going from a piece of DNA to the brain to behavior to the concept of gender, I mean, it's miles and miles in between each of those steps. You know, so it's a long way to go to understand any of this, but it means that for us scientists, there's lots of work to do, though.

Right, like hundreds of steps. Yeah, yeah, yeah, at least. So I say the definition of sex is really evolving. And what we're focusing on really is basically what's inside your brain. How is your brain structured? And so we're trying to understand how do these brain structures develop, basically. But it's not well understood. So I would say you can't even really define what gender and sex are right now.

So it's really hard to even define what the real. relationship between the two are. So, what does it mean to be a woman? The latest research is showing that female and male brains do develop differently in the womb, possibly giving us females this innate sense of being a woman. On the other hand, maybe it's our shared sense of commonality that makes us women. Becoming so many different shapes and sizes that asking what it means to be a woman may not be the right question. It's like asking a calico cat what it means to be a calico cat. Maybe becoming a woman means accepting ourselves for who we really are and acknowledging the same in each other. I see you and you've just seen me. That's Perissa Sanban Matsu. She's a structural biologist

at Los Alamos National Laboratory in New Mexico and you can watch her full talk at ted.com. Thanks so much for being here with me for this week's show on The Biology of Sex. If you'd like to find out more about who was on it, go to ted.npr.org. And to see hundreds more TED talks, check out TED.com or the TED app. Our production staff at NPR includes Jeff Rogers, Sanaz Mejkampur, Rachel Faulkner, Diba Motisham, James Delahousy, J.C. Howard, Katie Montalione, Maria Paz Gutierrez, Christina Kala, Hannah Balanos and Matthew Cloutier with help from Daniel Shukin. Our theme music was written by Romteen, Arablewe,

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