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Hey, everyone, it's Manou, there have been a lot of big headlines this summer, and that includes a landmark Supreme Court ruling in June protecting the rights of gay, lesbian and transgender workers. Society and the law are becoming more accepting of the different ways that people express their gender and sexual orientation. But we still have so much to learn about the science. What determines our biological sex? Many of us were taught that we're born either female or male, X, X or X Y.

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But as we explored back in an episode in May, it is far more complex if you missed this episode the first time around, or if you'd like another listen of this intriguing and complicated subject. Here's our Biology of Sex episode again. Thanks so much for being here. This is the TED Radio Hour.

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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, which we have to ask ourselves, like why is it noteworthy and even change you?

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I literally feel like I'm a different person. Yes. Do you feel that way? Ideas worth spreading. From Ted and NPR. I'm a new shahmoradi 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 grownup. Some of the things we talk about could be a little confusing. OK, 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?

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Yeah, I grew up in Salt Lake City, Utah. I wasn't a Mormon, but I grew up surrounded by the Mormon culture.

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I guess this is artist and activist Emily Quinn. In that culture, women are expected to get married, have kids like it, feels like you're groomed from a very early age for motherhood, and they equate motherhood to 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.

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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 traumatic because I was right when the maturation program was happening at school. And is that like sex ed was 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.

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Like, I remember we went into the half of the auditorium and like 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 like I already knew at that point.

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Can we talk about what the doctors told you? You were told that you had a disorder, is that correct?

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Yes, I told I have a disorder of sex development. Pretty sure it was androgen insensitivity syndrome. That was all the language that they used. The term intersex I didn't hear for a long time.

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Emily Quinn continues her story on the TED stage.

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I have a vagina I should know that might not come as a surprise to some of you. I look like a woman dressed like one.

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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 slow.

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But I'm not talking about bravery or courage. I mean, literally, I have balls right here, right where a lot of 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 are so many ways somebody could be intersex, and in my case, it means I was born with X Y chromosomes, which you probably know as male chromosomes, and I was born with a vagina and balls inside my body.

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I don't respond to testosterone. So during puberty I grew breasts, but I never got acne or body hair. Body oil. You can be jealous of that.

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But even though I don't actually have a uterus, I was born with that 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 the society. We love putting people into boxes and labeling each other. It kind of 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.

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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 we're assigned at birth, because despite what most of us were taught in health class, there's more to it than just female or male, X, X or X, Y.

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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 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 your very feminine and like, super pretty sorry. Hope that's not buy me dinner first.

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But you are like you present is like an extremely feminine woman.

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And so for I think there's something about it being you explaining this to people that is.

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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?

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It's confusing.

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No, we haven't learned how biology really works. Right.

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And that's the that's the truth of it, is that there's it's so much more complex. So when I talk about sex and biological sex, I specifically talk about seven different areas. And people will talk about this in all in all various ways. I talk about the seven areas being your chromosomes, your gonads like testicles 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, etc.

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, 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 whose 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.

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I mean, like you said, I definitely started dressing more girly and feminine early. And that was more for 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 two percent of the population.

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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 US. She found out she was intersex at age forty one.

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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. It's kind of thing happens a lot where intersex people are lied to or kept in the dark about our bodies. It's rare to meet and 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.

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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.

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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?

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What I really wanted was somebody saying, hey, look, this is going to be OK. Like, that's not a big deal. And it's not like that life changing because that's the thing.

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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 that would have meant I belong to 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.

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And so if I had somewhere that I fit in and that I belonged and I didn't just constantly feel like an impostor, that would have been huge.

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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 ballsy.

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And like, you know, you can't help but laugh because 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 I wonder if that's what's happening is you're exploring that crack and that that must if that's the case, that sounds like a lot of work.

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You're making me cry. No, it's OK. 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.

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And I didn't realize how much I held in my body. Um, yeah, it's a lot.

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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, um, 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.

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Emily Quinn, you can find her full talk at Ted Dotcom on the show today, ideas on the biology of sex. I'm a new Sumathi and you're listening to the TED Radio Hour from NPR. Everyone, just a quick thanks to two of our sponsors who helped make this podcast possible, first to E-Trade, trading isn't for everyone, but E-Trade is whether it's saving for a rainy day or for your retirement.

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E-Trade has you covered. They can help you check financial goals off your list. And with a team of professionals giving you support when you need it, you can be confident that your money is working hard for you to get more than just trading with ETrade to get started, visit ETrade dot com slash podcast for more information. ETrade Securities LLC member FINRA SIPC.

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Black voters play a crucial role for any Democrat who seeks to win the White House, but some big divides amongst that bloc and some serious ambivalence could determine who is elected president this November. Listen now on the Cosulich podcast from NPR. It's the TED Radio Hour from NPR. I'm Anoush Summer zeroed and on the show today, the biology of sex, because it's more complicated than just female or male X, X or X Y.

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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 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 and Y, so you can be X, X, Y, be X, Y, Y, can be X.

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Oh. Hmm. I mean, it just goes on now is like things that I thought were just like immutable biological truths can be changed in some way.

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A lot of these kinds of questions came up for Molly while she was working on a series called Gonads.

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Episode three. I'm Molly Webster for the show Radiolab. You're listening to Radiolab.

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When they found these chromosomes was clear that if you had X, 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. Boy, that was the thinking.

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So you see, Roger on that is not wrong.

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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.

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Why do we have such a simplistic view of biological sex?

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It's a specific way of thinking about things from a certain moment in history that we are potentially starting to rethink.

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I think it's helpful to see sort of like 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 twenty third pair of chromosomes decides our sex. For me, the true story of X and Y starts with their name.

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Here's Molly Webster on the TED stage, along with some voices of scientists she taped while reporting on her series.

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So within years of being discovered, these two little chromosomes had acquired more than 10 different names.

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There was diplo some and hetero chromosome, an ideal chromosome, and most of the names had to do with their structure, their shape, their size.

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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.

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But scientists were like, do we really want to call them sex chromosomes? And science historian Sarah Richardson is the one who told me the story.

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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.

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They ended up getting sex chromosome, but in the 100 year history since we settled on that name, you can see it start 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.

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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.

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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.

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So I'm feeling like a rising sense of foreboding here.

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Based on what you mentioned earlier about why the scientists were concerned about naming at the sex chromosomes, like what were the implications of calling them sex chromosomes?

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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 weight, a super male. Yeah.

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So the theory goes, if at that time or even today, if we're really believing that Y is male and 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.

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Ha! So a few years after they realized that you can be X, Y, y, 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 X, Y, Y.

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And according to Sarah, they just rushed to publish a theory suggesting that this extra Y chromosome could explain criminality in some men.

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Yeah. So the logic goes like this. By this point, we're thinking, why is male? We think male is aggressive. So y must be aggression. If you've got an extra Y, you must be crazy. And like, we went nuts with this theory. We called it the super male.

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They started scanning more prisoners, serial killers, boys. And in all seriousness, there's actually a suggestion that we consider aborting X, Y, Y fetuses.

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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.

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And then there was one other thing. Going back and looking at those original findings in 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 Y.

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Now, they never claimed that the individuals with an extra X chromosome were super females.

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They never investigated whether they had higher rates of violence. Seems like kind of an oversight.

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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 as we look at them through the lens of gender and the traits that we associate with gender.

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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.

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And so I think all of us in the world are trying to understand, like, what assumptions and am I making these days based on old fashioned ways of thinking about what sex and gender are?

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It's it's an interesting question, and 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.

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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.

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But one thing that we all have to have is the x ray like. Yeah. So one thing 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 ray 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.

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Yeah. It's so tightly associated, X with femaleness and Y with maleness. 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?

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Of the almost 1100 genes on the X chromosome, how many do you think have to do with sex and reproduction? It's like get a number in your head, four percent.

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That means ninety six percent of the 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.

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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?

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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.

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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?

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I think we're still many steps away. You can see that society is in a very different place and I think than what's happening in some labs right now. And part of that has to do with the 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.

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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.

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Oh, that's Molly Webster. She's a radio journalist on the show Radiolab. Her series is called Gonads. And you can listen to her full talk at Ted Dotcom. 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?

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There are many theories on how women's brains differ from men's brains. That's neuroscientist Lisa Mosconi on the TED stage. I've been looking at brains for 20 years, pink and blue, Barbie and Llegar. Those are all inventions that have 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.

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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 organs are not equally prepared, perhaps, to think about the brain.

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Hormones allow the brain and the reproductive organs to talk to each other, and that conversation is crucial.

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So from a scientific perspective and 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 brain. So if you have an X X 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 is going to grow more and more.

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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 X Y, then the Y chromosome contains genes that will make your body produce androgen like testosterone. And that means that your brain is going to optimize for 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 and androgen receptors.

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So structurally, these brains are a little bit different or biochemically his brains are a little bit different from the moment they're born. Most people think of the brain as some kind of blackbox isolated from the rest of the body.

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But in reality, our brains are in constant interaction with the rest of us. These interactions are mediated by your hormones and we know the hormones differ. Men have more testosterone. Women have more estrogen. So the brain is connected to the reproductive systems via a network that is called the neuro endocrine 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.

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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 estrogen 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 the key then is to open a specific lock you in. These locks are called receptors.

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So you, for example, in the female brain, there are very specific parts of the brain that are very dense with receptors and that's where the hormones go. They bind to the receptors, then they kind of turn them on and that generates a million different things. That Brain Energy's power. You have more immunity, then more resilience against disease. You have more plasticity, you have more growth in all these hormones together are responsible for the menstrual cycle in women in their connected to the ovaries.

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You're going into the system and in men, obviously, they're they're connected to the testes. So these systems are really important and different structures are connected to each other via the hormones, the flow back and forth every day of her life. So it's not just reproduction. There are so many things they need to happen inside the brain that are really facilitated by these hormones.

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More from Lisa Mosconi on how our brains develop differently. We're talking about the biology of sex. I'm Anoush Zamora's and you're listening to the TED Radio Hour from NPR.

[00:33:24]

Stay with us. Oh. Support for this podcast and the following message come from the American Jewish World Service, working together for more than 30 years to build a more just and equitable world. Learn more at A.J. W.S. Dawg. Back in the day, as Netflix began to gain popularity, its rival, Blockbuster, was looking for an edge. At one point, the investors were asking Blockbuster to sell jeans in the store.

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Yeah, you just in like older investors being like, you know what the kids want? They want jeans.

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You get a Tom Cruise movie and some stonewashed jeans. The downfall of Blockbuster and the rise of Netflix.

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Listen to it's been a minute from NPR. It's the TED Radio Hour from NPR, I'm Anoush zeroed in on the show today, The Biology of Sex. We were just talking to neuroscientist Lisa Mosconi 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 like when it comes to the brain and hormones?

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Because we've been gathering on this episode about X, X, Y or X, Y, Y people.

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And earlier we spoke to Emily Quinn, who shared her personal story about how she is intersex, that she is X Y, but actually her body doesn't respond to testosterone, only estrogen, which from your description seems like it would be a response to X X chromosomes. But she has X Y chromosome. So I guess I'm wondering, like, is there a spectrum?

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

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Like a lot of people ask me if I if I give you a brain scan and you just look at the brain scan, can you tell me that brain belongs to a man or a woman? Was I? No, of course not. Yeah. No, you cannot you cannot do that. But then what?

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How do you know the difference? When when's the moment when you're like, oh yes, this is female or oh yes, this is a male brain.

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In my experience, the most defining feature is the change over time, starting in the 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 declines 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.

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Forty five forty eight women are much more likely than men to have lower metabolic activity in their brains. In their brains, yes. In their brains.

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OK, so as a woman barreling towards her late 40s, that gives me great pause, because exactly what you're saying is that a man my age is pretty much going to have the same brain his whole lifetime.

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But as a woman, I my brain is going to go through a change because my body responds to hormones differently, correct?

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Yes. Yes. And it's not just menopause. I think we tend to 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 enormous amount of estrogen. And that has really been shown to change the structure, the function and the connectivity of the brain in both teenage boys and girls in adolescence.

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And what's interesting is that these remodelling 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 optimisation.

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So the brain is getting rid of all the neurons that it doesn't really cleaning house, OK? Yes, exactly. So you're doing a nice cleaning. You're like, OK, at this point, you know how to tell you she's so I don't need these neurons anymore. You can do it by yourself, huh? 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.

[00:38:40]

The brain goes through a remodelling after the baby's born. 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 neurons and synapses that I don't know, because it felt like that.

[00:38:58]

I felt like my I, I felt like I had a different head on my shoulders after I had a baby. Yeah. For good and bad. 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 that gave it gave my brain a big old shower. And I emerged as a kind of a little bit of a different person, I guess.

[00:39:24]

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 this changes. The symptoms do not start in the ovaries as many people think they start in the brain.

[00:39:49]

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?

[00:40:01]

It's in part genetic, but also a big part is really whatever happens after you're born.

[00:40:08]

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 brain. Number three, how does 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 just different. Just about pink and blue or what kind of toys we like or what kind of jobs we want to have is really it's not just gender role.

[00:40:42]

It's a sort of health. That's neuroscientist Lisa Mosconi. Her latest book is The Brain. You can see her talk at Ted Darkon. 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.

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And we may not find out for a long time looking more and more into the research.

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You know, there is so many open questions. So we're trying to understand now, but there's no smoking guns yet at all.

[00:41:21]

This is a structural biologist, Christesen man, Matsue. 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.

[00:41:34]

But before turning to biology, Charissa study lots of things.

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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 getting into chaos theory, complex systems and non-linear theory.

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And then I did laser fusion.

[00:41:52]

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.

[00:42:01]

And the reason why Charissa went from studying the stars to studying what determines biological sex is a personal one.

[00:42:09]

Here's Carissa on the TED stage. When people learn that I'm a woman who happens to be a 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. Charissa 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.

[00:42:44]

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.

[00:42:57]

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 pastiches talks before, but this one I was terrified. I looked out into the audience and the whispers started the stares, 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 OK.

[00:43:36]

I'm OK now. But I found enough is enough, I'm a scientist, I have a doctorate in astrophysics, I published in the top journals and wave particle interactions, space physics, nucleic acid biochemistry. I've actually been trained to get to the bottom of things.

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From there, I started delving into, you know, why am I transgender and so forth. And I think that if if we can show people that it's something legitimate, then maybe people will take this a lot more seriously.

[00:44:15]

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 DNA. Right. Like epigenetics, that that could be the thing that makes us male or female or maybe CIS gender or transgender.

[00:44:33]

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 that 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.

[00:45:06]

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 Chris said, epigenetics reprograms are genes deciding the path our DNA takes?

[00:45:23]

Yeah, and I think path is really the operative word here that you hit on. And so there's something called Waddington's, a landscape where Waddington's landscape. I love this. It's kind of a well-known analogy about epigenetics.

[00:45:37]

So imagine your cells are marbles rolling down a hill, developing, deciding what to eventually turn into.

[00:45:44]

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.

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And scientists like Charissa 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.

[00:46:19]

Yeah, because actually I heard this because I had a conversation with the 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.

[00:46:45]

So that's a current working model that many people subscribe to and 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.

[00:47:19]

OK, as Charissa 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.

[00:47:36]

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.

[00:47:45]

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.

[00:47:56]

To truly understand DNA decision making, we need to see the process in atomic detail. Even the most powerful microscopes can see this. What if we try to simulate this on a computer? We need a million computers to do that.

[00:48:13]

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.

[00:48:39]

For the first time, we're beginning to understand the unsolved problem of hormones triggered the formation of these knots. OK, 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 is a super vast and complicated field of biological sex and then how that connects to gender.

[00:49:13]

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 it's a long 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?

[00:49:42]

Like hundreds of steps. Yeah, yeah.

[00:49:45]

Yeah, yeah. At least. So there's 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 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 relationship between the two are.

[00:50:14]

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.

[00:50:29]

On the other hand, maybe it's our shared sense of commonality that makes us women. We come in 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.

[00:50:47]

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 paresis and Bonamassa. She's a structural biologist at Los Alamos National Laboratory in New Mexico, and you can watch her full talk at Ted Dotcom.

[00:51:16]

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 Unpeg and to see hundreds more TED talks, check out Ted Dotcom or the TED app. Our production staff at NPR includes Jeff Rogers, Sanaz Myshkin, poor Rachel Falkiner Deba MultiCam, James Delahoussaye, J.C. Howard, Katie Montalbán, Maria Paz Gutierrez, Christina Kollar, Hannah Bolaños and Matthew Kutya with help from Daniel Shukan.

[00:51:49]

Our theme music was written by Rob Era Blooey and our partners at Ted are Chris Anderson, Colin Helmes, Anna Felin and Michelle Quent. I'm Anoush Samadhi and you've been listening to the TED Radio Hour from NPR.