MANOUSH ZOMORODI, HOST:
On the show today - the biology of sex.
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ZOMORODI: 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.
KARISSA SANBONMATSU: 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.
ZOMORODI: This is structural biologist Karissa Sanbonmatsu. 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.
SANBONMATSU: 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, 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.
ZOMORODI: And the reason why Karissa went from studying the stars to studying what determines biological sex is a personal one. Here's Karissa on the TED stage.
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SANBONMATSU: 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.
ZOMORODI: Karissa was assigned the male gender at birth. About a decade ago, she transitioned to female. But her new life was sometimes painful.
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SANBONMATSU: 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 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 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. I'm OK now.
SANBONMATSU: But I felt, enough is enough. I'm a scientist. I have a doctorate in astrophysics. I've 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.
ZOMORODI: 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 cisgender or transgender.
SANBONMATSU: 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.
ZOMORODI: So we're all born with our DNA. But our environment can change the way our DNA is expressed. So just like Karissa said, epigenetics reprograms our genes, deciding the path our DNA takes.
SANBONMATSU: Yeah. And I think path is really the operative word here that you hit on. And so there's something called Waddington's landscape...
ZOMORODI: OK. 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.
SANBONMATSU: 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.
ZOMORODI: And scientists like Karissa are trying to understand how epigenetics might change the path our cells take as our bodies develop in female or male ways in utero.
SANBONMATSU: 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.
ZOMORODI: 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?
SANBONMATSU: 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.
ZOMORODI: OK. As Karissa 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.
SANBONMATSU: 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.
ZOMORODI: 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?
SANBONMATSU: Exactly. Exactly.
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SANBONMATSU: To truly understand DNA decision-making, we need to see the process in atomic detail. Well, even the most powerful microscopes can't see this. What if we tried to simulate these on a computer? We'd 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 of how hormones trigger the formation of these knots.
ZOMORODI: 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.
SANBONMATSU: Yeah, that's right.
ZOMORODI: 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 gender, and you're each just trying to figure out one step, right?
SANBONMATSU: 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 - 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.
ZOMORODI: Right, like, hundreds of steps.
SANBONMATSU: Yeah, yeah, yeah, yeah, at least. So there's - I'd say that 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 relationship between the two are.
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SANBONMATSU: 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. 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 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.
ZOMORODI: That's Karissa Sanbonmatsu. 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 Meshkinpour, Rachel Faulkner, Diba Mohtasham, James Delahoussaye, J.C. Howard, Katie Monteleone, Maria Paz Gutierrez, Christina Khala, Hanna Bolanos and Matthew Cloutier, with help from Daniel Shukin. Our theme music was written by Ramtin Arablouei, and our partners at TED are Chris Anderson, Colin Helms, Anna Phelan and Michelle Quint. I'm Manoush Zomorodi, and you've been listening to the TED Radio Hour from NPR.
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