Jun 30, 2018

Gonads: X & Y

A lot of us understand biological sex with a pretty fateful underpinning: if you’re born with XX chromosomes, you’re female; if you’re born with XY chromosomes, you’re male. But it turns out, our relationship to the opposite sex is more complicated than we think.

And if you caught this show on-air, and would like to listen to the full version of our Sex Ed Live Show, you can check it out here

This episode was reported by Molly Webster, and produced by Matt Kielty. With scoring, original composition and mixing by Matt Kielty and Alex Overington. Additional production by Rachael Cusick, and editing by Pat Walters. The “Ballad of Daniel Webster” and “Gonads” was written, performed and produced by Majel Connery and Alex Overington.

Special thanks to Erica Todd, Andrew Sinclair, Robin Lovell-Badge, and Sarah S. Richardson. Plus, a big thank you to the musicians who gave us permission to use their work in this episode—composer Erik Friedlander, for "Frail as a Breeze, Part II," and musician Sam Prekop, whose work "A Geometric," from his album The Republic, is out on Thrill Jockey.

Radiolab is supported in part by Science Sandbox, a Simons Foundation initiative dedicated to engaging everyone with the process of science. And the Alfred P. Sloan Foundation, enhancing public understanding of science and technology in the modern world. More information about Sloan at www.sloan.org.


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MOLLY WEBSTER: Gonads, episode three. I'm Molly Webster.




MOLLY: Hello, are you still there?


MARY WEBSTER: I'm still here.


MOLLY: And this is my mother, Mary Webster.




MOLLY: But -- but yeah, the bedbugs are such a freaking pain.


MARY WEBSTER: Oh, it sounds awful.


MOLLY: You have to vacuum all of the baseboards, you have to vacuum the floors. You have to vacuum the doorjambs because they crawl up the walls when they're trying to get away.


MARY WEBSTER: Oh, Molly, that sounds awful!


MOLLY: So I recently called my mom for -- I guess to catch up, but also ...


[GONADS MUSIC: I'm calling from the other side.]


MOLLY: I had a work question. [laughs]


[GONADS MUSIC: Did you ever stop and wonder why?]


MOLLY: That's been bugging me.


[GONADS MUSIC: A part of you was left behind.]


MOLLY: Was on my mind.




MOLLY: So I asked her, "Mom, I've been working on this story. And it made me wonder what you would have named me if I was a boy."


MARY WEBSTER: You would have been named Daniel.




MARY WEBSTER: Dad always liked the name. And if we ever had a boy, Dad said he was gonna name him Daniel. And I said, "Oh! If that's what you want, go for it," you know? Because he didn't want a Junior, he wanted a Daniel. He wanted a little Danny.


MOLLY: Instead, he got a Judy, Chrissy, Peggy and Molly.


JAD: Your poor father.


MOLLY: The -- my lucky father!


MARY WEBSTER: If you had come out boys, you would have been Daniel, yes.


MOLLY: Wait. All of us?


MARY WEBSTER: No. Well, you see -- no, we wanted Daniel for a boy. Not for everybody.


MOLLY: You were just ready.


MARY WEBSTER: Yeah, well we didn't know. When a boy came out it was gonna be a Daniel, you know what I mean? That was it.


MOLLY: So this is just gonna sound ridiculous, but I called my mom because all these stories that we've been doing in this series, they do make you think about fate. Like, even if you think about the first one where they're the primordial germ cells and they're holding on to all sorts of possibilities and futures, and then ...


[GONADS MUSIC: Chromosomes.]


MOLLY: Chromosomes step in and -- poof -- no more infinity. You're just, like, shunted onto a path. I guess -- I guess asking my mom about Daniel was just, like, a clumsy way of getting back to what feels like a really pristine moment. Like a moment where no decision had been made. Where you exist totally unblemished by life and choice and fate. Unless maybe life isn't so fateful.


DAVID ZARKOWER: [clears throat]


MOLLY: Case in point, David Zarkower.






DAVID ZARKOWER: Actually, I'm just going to -- I don't like correcting people, but I'll just correct you. My name is pronounced Zarkover.


MOLLY: Zarkover?


DAVID ZARKOWER: Zarkover, yep.


MOLLY: Because it is a 'w,' right? I'm not misspelling it in my head.


DAVID ZARKOWER: It's a 'w,' yeah. Just, you know, for the sake of my parents I pronounce it with, like, a 'v.' It's essentially Polish.


MOLLY: That's good. And you work at the University of Minnesota?


DAVID ZARKOWER: Yep. That's right.


MOLLY: What do you do there?


DAVID ZARKOWER: Genetic cell biology and development.


MOLLY: That's -- that seems scary.




MOLLY: Anyways, the reason I called Zarkower was because I came across a series of experiments that he did that just straight up kicked me in the gonads.


DAVID ZARKOWER: Okay, so ...


MOLLY: To begin ...


DAVID ZARKOWER: This was back in the early 1990s.


MOLLY: Zarkower was working in a lab doing genetic stuff.


DAVID ZARKOWER: In worms and flies and mice and things. And ...


MOLLY: One day ...


DAVID ZARKOWER: Presto. We got lucky.


MOLLY: Da da da da!


MOLLY: He and his team discovered a brand new gene.


DAVID ZARKOWER: Yep. That's right.


MOLLY: They saw it in mice and gave it a name.


DAVID ZARKOWER: I, unfortunately, I'm responsible for this. It's DMRT1.






MAN: Demert-one.


MOLLY: I keep trying to say DRMT ...


DAVID ZARKOWER: Yeah, it's -- it's a nightmare. I'm very sorry for that.


MOLLY: And what was interesting was that this gene was in mice ...


DAVID ZARKOWER: But also in humans.


MOLLY: And in the male mouse, it was expressing itself in the testes. I never know how to say it. Testis?


JAD: Testes? Testes.


MOLLY: Testes? Testicles?




MOLLY: Is that a single?




JAD: Hmm.


MOLLY: Okay.


DAVID ZARKOWER: So, yeah. So we found this gene, and humans had it in the testis. And the question we had was whether it was doing something or not.


MOLLY: Like, you've got genes in your eyes that are making chemicals that are making your eyes the color they are.


DAVID ZARKOWER: This gene, DMRT1 ...


MOLLY: What is it doing?


DAVID ZARKOWER: We wanted to know if it's involved in maybe making sperm.


MOLLY: Or ...


DAVID ZARKOWER: Maybe it just hangs around, it doesn't matter.


MOLLY: It doesn't do anything.


DAVID ZARKOWER: You know, we don't know.


MOLLY: And so they're like, "Let's mess around with it and see what happens." But you can't do that experiment in humans.




MOLLY: So instead, they get some adult male mice.


DAVID ZARKOWER: Perfectly normal, fertile males.


MOLLY: That are making sperm.


DAVID ZARKOWER: And we use some fancy molecular genetic tricks.


MOLLY: And so basically ...


DAVID ZARKOWER: It's kind of mean trick, but it's genetics.


MOLLY: They cut the gene out, and then they take a slice of the testis and they look at it under the microscope.


DAVID ZARKOWER: And it didn't look like what we would have expected.


MOLLY: And what they expect to see is that these are the cells that help make sperm in the testis, and normally they're kind of tall and lean.


DAVID ZARKOWER: Long and skinny.


MOLLY: But suddenly ...


DAVID ZARKOWER: They were different.


MOLLY: With DMRT-1 gone, they had gotten smaller and rounder. And Zarkower was like ...


DAVID ZARKOWER: This was not something that was supposed to happen.


MOLLY: What is going on here?


DAVID ZARKOWER: What are these things?


MOLLY: And then he realized that the cells are making estrogen, and he was like, "Oh, I think what is happening is that the cells in the testis turned into ovary cells."


JAD: Wait, what?


MOLLY: And ...


JAD: Wait. This is a male mouse.




JAD: So you're saying this male mouse now has ovary cells in its testicles?


DAVID ZARKOWER: Yes, this -- these are cells that are changing their sex.


MOLLY: That's insane! Can we just have, like, an exclamatory moment? Like where you -- where you like, "Whoa, is that -- that's possible that happened?" What is -- you know?


DAVID ZARKOWER: What do you say? For us anyway, the greatest of all scientific exclamations is, "That's weird!" So we had a "That's weird" moment.


MOLLY: And just to take this weirdness, like, one step further, a group of scientists did a similar experiment in adult female mice where they did, like, the same ...


DAVID ZARKOWER: Fancy molecular genetic tricks.


MOLLY: Only this time, they knocked out a female gene in the ovary. And when they went to look at it ...


DAVID ZARKOWER: The ovary is trying to kind of reorganize itself into a testis.


JAD: Wait.


MOLLY: Mm-hmm?


JAD: You're saying in both cases, there is one gene that's flipping the sex from male to female or back?




JAD: One gene.


MOLLY: One gene.


JAD: How many genes do we have in our body?


MOLLY: I don't know. Like, tens of thousands?


JAD: Whoa. And just one is doing this.


MOLLY: Which is ...


JAD: Weird.


MOLLY: A weird concept to think of, because we typically connect, like, sex or gonads to chromosomes. At least I do. Like, an X and a Y.


JAD: Right.


MOLLY: Is a girl and a boy. So how could a gene step in and reverse that?


JAD: Yeah, because I thought chromosomes were lots of genes. They were these, like, massive things. One gene is so tiny.


MOLLY: Genes are tiny, chromosomes are much bigger. And I think the answer to that is that, when you get down to sex, like what makes us one sex or the other, it's not -- it doesn't work exactly like we thought. Like, take for example the X and Y idea. This, like, chromosomal narrative we have 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.


JAD: Huh.


MOLLY: I think it's helpful to see sort of like the history of how we understand sex in -- in a longer time-frame. So let me bring in this guy.


DAVID PAGE: I'm David Page, biology professor at MIT.


MOLLY: Okay, where do we start?


DAVID PAGE: Oh, my gosh. Well, we're gonna go -- so let's see, we could go off the rails in any number of directions here, all of which would be quite -- quite productive. But let's see. So let's go back to the 1890s.


MOLLY: Yeah, that definitely is 1890s.




MOLLY: So genetics was in its infancy. Mendel, peas, all that was happening.


DAVID PAGE: And people had been pondering for millennia, where do boys and girls come from?


MOLLY: Now when it came to how you look, people thought, Mom and Dad? Clearly involved.


DAVID PAGE: Because people had realized, you know, that children ended up growing up looking something like their mother and their father.


MOLLY: Like maybe you have a chin like your dad, and nose like your mom, and hair that's a little bit of both.


DAVID PAGE: There was a kind of blending ...


MOLLY: Of mom and dad to make you you.


DAVID PAGE: Right. But ...


MOLLY: When it came to why you were the sex you were?




MOLLY: That was a mystery.


DAVID PAGE: Because ...


MOLLY: There was no blending.


DAVID PAGE: You ended up being like either your mother or your father.


MOLLY: One or the other.


DAVID PAGE: Therefore, it must not have anything to do with heredity. It had to be imposed from the outside in some way.


MOLLY: So people came up with all kinds of ideas for what made you a boy or a girl.


DAVID PAGE: The phase of the moon at the moment of conception.


MOLLY: Cold dark moon? Definitely a girl.


DAVID PAGE: The state of the economy.


MOLLY: Wouldn't be surprised, down economy? Girl.




MOLLY: Everything that was bad was given to women. There was what the mother ate, mom's body heat, stress.


DAVID PAGE: All sorts of crazy things. And then in 1923 ...


MOLLY: We started looking elsewhere ...


[SCIENCE FILM CLIP: But how do we inherit our characteristics?]


MOLLY: ... for an answer.


[SCIENCE FILM CLIP: Chromosomes ...]


DAVID PAGE: Chromosomes.


MOLLY: Chromosomes.


[SCIENCE FILM CLIP: ... determine our physical appearance and our sex.]


MOLLY: In 1923, a scientist looking down the barrel of a microscope discovers two new chromosomes.


DAVID PAGE: An X and a Y.


[SCIENCE FILM CLIP: Called the sex chromosomes.]


MOLLY: But I just want to hit pause here.


JAD: Okay.


MOLLY: I came to find out, actually from David Page, that the X and Y chromosomes do not look like an X and Y.


JAD: Wait. They don't look like the letters?


DAVID PAGE: Oh, no, no, no.


MOLLY: No, when they first discovered them.


DAVID PAGE: They were blobs.


MOLLY: Under the microscope, they just looked like these misshapen clumps.


DAVID PAGE: I'd say kidney bean-like.


MOLLY: The X looked bigger, the Y looked smaller, but that's it.


JAD: That's so interesting, because there's something about the shape of the X and the shape of the Y which read as gendered letters.


MOLLY: That feels so -- yeah.


JAD: Yeah, because, like, the Y has a little stem on it, which is sort of penis-like.


MOLLY: Penis-like. There's, like, a duality or something in the X which feels like, you know, ovaries and breasts or something. Like, there is, like -- there is something about those letters. So I was totally shocked when he was like, "There's no real reason they got those letters. It was totally arbitrary." Anyways, when they found these chromosomes ...


DAVID PAGE: It was clear that if you had ...




DAVID PAGE: Two X chromosomes, you would develop as a female.




DAVID PAGE: Anatomic female. And if you had a y chromosome ...


MOLLY: So your X, Y.


DAVID PAGE: You would develop as an anatomic male.


[SCIENCE FILM CLIP: That's right. A boy.]


DAVID PAGE: That was the thinking.


[SCIENCE FILM CLIP: So you see, Roger and Susan are born ...]


MOLLY: But then that idea, it got more complicated.




MOLLY: Yeah, when did you intersect with this story?


DAVID PAGE: The summer of 1979.


MOLLY: Page was at MIT.


DAVID PAGE: First year of medical school. And the DNA revolution ...


[NEWS CLIP: So far tonight, we've been bringing you news of the world around us.]


DAVID PAGE: ... was just beginning.


[NEWS CLIP: Now, we have news of the incredible world inside us.]


MOLLY: He was involved in what he describes as, like, the precursor ...




[NEWS CLIP: The Human Genome Project.]


DAVID PAGE: What would become the Human Genome Project. Working with a group of senior scientists who were envisioning maps of the human genome.


[NEWS CLIP: An encyclopedia of man. We'll know the complete set of instructions which make people.]


DAVID PAGE: And we began to look back at some exceptional human individuals who had not been understood previously.


[NEWS CLIP: That saliva test ...]


DAVID PAGE: Women ...


[NEWS CLIP: ... revealed that Maria had a set of X and Y chromosomes ...]


DAVID PAGE: ... who had an X and Y chromosome.


[NEWS CLIP: ... like most men. Women usually have a pair of Xs.]


MOLLY: And they were also looking at men ...


DAVID PAGE: Who had an altogether male anatomy.


MOLLY: Penis, testes.


DAVID PAGE: But whose chromosomes appeared to be those typical of a female.


MOLLY: XX. And for Page and other scientists they're like, "Oh, there must be something more happening here than just, like, the chromosome. There must be something deeper going on here."


DAVID PAGE: So we might actually be on the trail now of the secret.


MOLLY: So scientists across the world start looking at these people's chromosomes.


DAVID PAGE: And what we found was that a few XY females were actually missing a little bit of the Y chromosome.


MOLLY: With these XY women, a little bit of the Y wasn't there.


DAVID PAGE: And the bit of the Y that the XY females were missing was the same bit that was present in the XX males.


MOLLY: Meaning somehow, a little bit of the Y chromosome had gotten onto one of the Xs of these XX males.


DAVID PAGE: And so it was becoming very clear that this must be the bit that matters.


MOLLY: And around 1990 ...


[NEWS CLIP: Other news this day, scientists say they've made a major discovery ...]


MOLLY: Scientists in Britain announced they'd found this one gene on the Y chromosome.


[NEWS CLIP: The genetic trigger on the Y chromosome that determines whether a baby will be a boy or a girl.]


MOLLY: What they found is that, of the 200-odd genes on the Y chromosome, there was this one single gene that acted as the switch.


[NEWS CLIP: The master switch ...]


DAVID PAGE: The grandmaster switch.


[NEWS CLIP: ... which determines the child's sex.]


MOLLY: So it's not X and Y as a whole, it's one tiny piece. So back in the first episode, there were those primordial germ cells. And they had to go on that super long journey to get to the gonad cathedral. And on the journey, when they got to the cathedral they were full of potential, right? They could be anything. They could be male, they could be female, they could be whatever your version of anything is. And then when they get there, there's a moment where, like we said, fate stepped in and just -- whoosh! -- like, swept all their possibility away and said, "You are one thing, and this is the thing you will be," This gene is fate. This gene these scientists discovered, if it shows up then you shoot off down the path that is sperm, testis, male. And if it doesn't show up, you shoot down the path of egg, ovary, female. And the scientists gave this gene a name, SRY.


JAD: Uh-huh.


MOLLY: Which is like, "Sorry." It was like, "You're a man. Sorry!"


JAD: So it sounds like we've gone from, like, crazy ideas about what makes a boy or a girl, to chromosomes, to now, like, this little gene.


MOLLY: Yeah.


JAD: But the SRY gene that you just mentioned is different than the gene that I just heard about from -- I forget his name.




MOLLY: Zarkower.


DAVID ZARKOWER: Zarkower, yeah.


MOLLY: Zarkower.


JAD: Zarkower, yes.


MOLLY: It is. I think ...


JAD: It's different? Is that the same gene? Or is it ...


MOLLY: DMRT-1 is a different gene than SRY. But this -- this is what's so crazy about DMRT-1. Okay, primordial germ cells, they're in the embryo. They're waiting to become something, and then SRY shows up.


DAVID PAGE: But just comes on for about a day, and then it goes away.


MOLLY: But once it turns on, it then starts this, like, cascade of gene after gene after gene that all sort of say, "You're male, you're male, you're male." And what all of these genes do is they create chemicals that send out signals that start forming and shaping the testis.


DAVID ZARKOWER: And as soon as the testis begins to develop.


MOLLY: On turns the fourth gene.




MOLLY: Zarkower's gene.


DAVID ZARKOWER: And it clearly is important for finishing the job of making a testis.


MOLLY: But the thing is, most of these other genes that make the testis turn off, but DMRT-1 ...


DAVID ZARKOWER: It doesn't go away at that point. It stays active.


MOLLY: Forever. In the womb when the testis is just growing, and then when you're born. And through, you know, childhood, your teenage years, adulthood. Like, until you die DMRT-1 is on. And if you take it away like Zarkower did, the cell will actually change sex. Which leads you to believe that DMRT-1 is actually preventing a cell from switching sexes.


BLANCHE CAPEL: That's right.


MOLLY: So I called Blanche Capel, who's the geneticist from our first episode. And she explained that what all this means is that that other path, the path that you did not take in the gonad cathedral, it never went away. It's actually still there. You carry it with you always. It's just that that gene has been shushing it.




MOLLY: Wait. I'm repressing the other pathway my whole life? Like ...


BLANCHE CAPEL: I think -- we think so. Yeah.


MOLLY: Really?




MOLLY: There's, like, a parallel universe male Molly?


BLANCHE CAPEL: [laughs] Yes, I -- I think there is. There's a parallel universe male Molly.


MOLLY: Wow! That's just cool!


JAD: Wait. When you say this gene has been shushing the other Molly, what does that even mean?


MOLLY: Huh. Okay, so you can think of it like this: the code for that other Molly, who I'll call Daniel, that code is still in my cells. And Zarkower says that what this gene does is it sort of -- one of the things this gene does is it sort of patrols and it makes sure that Daniel genes don't turn on.


DAVID ZARKOWER: Basically, what this gene's been doing it turns out, is playing whack-a-mole.


MOLLY: Basically just going around and being like, "Daniel, no. Off. Daniel, no. Off." Pew, pew, pew. And it does this maybe every day.


DAVID ZARKOWER: It's like an election that's always being kind of challenged. SRY cast the deciding vote, and male happened. But there's a recount every now and then. And if DMRT-1's not there to say, "Nope, still male," then you can go the other way.


JAD: So now I understand why you're so obsessed with Daniel, because -- because it's not just an idea, he's, like, trying to get out.


MOLLY: And it does go both ways. Like, you know, there's SRY and there's DMRT-1, but they have found these key genes in ovaries that you can turn on and off and have similar results.


JAD: Why would our -- why would our bodies be set up this way? Like, you'd think once a decision gets made that you just make that decision and be done with it. Why would there always be the possibility of unmaking the decision?


MOLLY: That is a good question, and I will answer that after break. But first, I'm gonna call my sisters. [laughs]


[KAYLA: This is Kayla Kabul calling from sunny Austin, Texas. Radiolab Presents: Gonads. Gonads is supported in part by Science Sandbox, a Simons Foundation initiative dedicated to engaging everyone with the process of science. Additional support for Radiolab is provided by the Alfred P. Sloan Foundation.]


[PAT WALTERS: Hey, everybody. Pat Walters here. I'm a producer at Radiolab, and I'm here because I need your help. This summer, I'm hosting a series of stories on the show and I have a request for those of you who spend a lot of time with kids: parents, aunts and uncles, teachers. We're looking for stories about what we're calling tiny moments of childhood brilliance.


PAT: Basically, I want to hear about those times when a kid you know did something that just made you lean back and say, "Whoa, how did they do that?" Maybe it was the moment that a kid you'd been reading to for months started reading back to you. Or maybe the kid was at piano lessons and you suddenly notice they were doing advanced math on the margin of their musical score. Or maybe the kid was in math class and you noticed they were writing music in the margin of their geometry homework. We're interested in those small, specific moments where a kid does something super-smart, but it doesn't have anything to do with a test. If you have a story, please share it with us and go to Radiolab.org/brilliance and record a short audio message for us. Again, that's Radiolab.org/brilliance. Thank you so much.]




MOLLY: All right back to Gonads. I'm Molly Webster.


MOLLY: Everyone say their name or hello.


CHRISSY: Okay, it's Chrissy.


PEGGY: Dude!


MOLLY: Peggy?


PEGGY: Yeah.


MOLLY: Hi. Hi, how are you?


PEGGY: I'm great.


MOLLY: And these are my sisters Judy, Chrissy and Peggy.


MOLLY: Okay, so I'll tell -- so I'm gonna tell you guys the thing. It's not even that big of a deal, but it's just sort of funny.


PEGGY: Oh, my God!


JUDY: Oh, no. Okay.


CHRISSY: You're pregnant.


MOLLY: I'm not pregnant. I'm not -- no, no. I just want to tell you about some reporting that I've been doing and then a funny thing that Mom and Dad told me. That's all it is.


JUDY: Okay.


PEGGY: Mom had an affair.


MOLLY: No! Oh, God. That would be ...


PEGGY: One of us doesn't belong. It's Chrissy.


JUDY: Yeah.


MOLLY: This is ridiculous. The third episode is basically about how we all carry in us, like, the opposite self that we never became. So -- so I called Mom because I was like, "What would male Molly have been like? Like, did you guys have, like, a name for male Molly?"


PEGGY: Mm-hmm.


MOLLY: And they were like, "Oh, we would have called you Daniel."


PEGGY: No! That was what they were supposed to call me. They were so desperate to use Daniel.


MOLLY: And it turns out that we were all supposed to be called Daniel.


JUDY: That's the big reveal?


MOLLY: It's not a reveal!


JUDY: There is an inner Daniel Webster.




JUDY: Jesus, Molly!


MOLLY: Oh, man! Are you surprised that your name would have been Daniel Webster? That you would have been a Daniel?






JUDY: No! I think you all knew that, right?


MOLLY: Peggy, did you know that?


PEGGY: I -- I didn't know that.


JUDY: I don't feel like my inner Daniel Webster would have that much of a different life than I have. So, but I think you guys, honestly -- not to railroad this conversation, but I think you guys lucked out because I was the one that was raised with the hopes that there was, like, some Daniel lingering in me.


CHRISSY: Isn't Daniel Webster like a famous dude in history?






JUDY: I took a picture of a statue of him once and send it to Dad, because I was supposed to be Daniel.


CHRISSY: Who is Daniel Webster?


JUDY: He's a boring, white dude.


MOLLY: Well, of course he is. We knew that part.


JUDY: He served as senator from Massachusetts and was the Undersecretary of State under three presidents.


PEGGY: Well, someone Googled fast.


JUDY: I think he's just a regular, like, old white lawyer dude.


PEGGY: Yeah, they're all racist. Or sexist or ageist or just a douchebag.


JUDY: [laughs] All right. Well ...


MOLLY: Great. Peggy got her giggles in. It's all been worth it. All right. That's all I got.


JUDY: We love you, Molly.


MOLLY: I love you guys. Goodbye.


PEGGY: Love you!


JUDY: Bye.


CHRISSY: Bye, Molly. You're amazing.


MOLLY: Okay, bye.


CHRISSY: I'm sorry about your bedbugs. Bye.


MOLLY: [laughs]


MOLLY: Okay, so to catch everybody up, we have learned that we are all carrying around with us another path. We all have our own inner Daniel Websters, and we're constantly shushing it. Or them. Whatever. So my question for Zarkower was like, why would I carry this path with me if I'm always turned -- like, if I'm just turning it off?




MOLLY: Do you have any answer to that?


DAVID ZARKOWER: I wish I had the answer. So the -- we don't really have an answer. It could be as boring as, well it doesn't really matter, because normally no molecular geneticist comes in and hacks out DMRT-1 or turns on FixL-2 or whatever. So why solve a problem that you haven't created? That -- that's quite possible, but boring. The more interesting answer is that this is an evolutionary holdover from a common ancestor with fish.


MOLLY: Okay, so this ancestor would be our great-grandparent 16 million times removed, which means 400 million years ago a fish swam out of the depths of the ocean, crawled onto land, and took, like, squelching steps forward and forward and forward and forward and forward through millions of years of luck and chance and fate until finally getting to you and me and ...


BOB WARNER: Ooh, hello?


MOLLY: Hello.


BOB WARNER: Can you hear me?


MOLLY: Yes, can you hear me?


BOB WARNER: Yes, I sure can.




BOB WARNER: My name is Bob Warner. I'm a research professor.


MOLLY: Studies evolution and marine biology.


BOB WARNER: At UC Santa Barbara.


MOLLY: What's your attraction to the ocean?


BOB WARNER: Well, the whole idea that there is a different world under there.


MOLLY: Well, I'm just going to Attenborough the shit out of this. So down in the waters around the Florida Keys, there swims a remarkable fish.


BOB WARNER: The bluehead wrasse.


MARSHALL PHILLIPS: It is a very common coral reef fish.


MOLLY: This is Marshall Phillips.


MARSHALL PHILLIPS: Graduate student at North Carolina State University.


MOLLY: She, like Bob, studies blueheads.




MOLLY: Anyways, down in the keys are some ...




MOLLY: Nice patches of reef.


BOB WARNER: That might have a group of, say, a dozen ...




BOB WARNER: And in that group, there will be a single large, brightly-colored male.


MOLLY: Just one of them.




MOLLY: About the size of your hand.


MARSHALL PHILLIPS: With a blue head.


MOLLY: And a shiny blue-green body.


MARSHALL PHILLIPS: It has white and black stripes right behind its head.


MOLLY: That go black-white-black.


MARSHALL PHILLIPS: That we very technically call the Oreo.


MOLLY: And if he's got a big Oreo?


MARSHALL PHILLIPS: Well, that's a sexy male [laughs].


MOLLY: And then the rest of the group is essentially a harem of lady-fish.


BOB WARNER: And the ladies in the group ...


MARSHALL PHILLIPS: Are little and yellow.


BOB WARNER: Very pretty.


MOLLY: That kind of swim a little slower, watching out for things.


BOB WARNER: Where the male is ...


MARSHALL PHILLIPS: Flashy. Darting all around.


BOB WARNER: Much more aggressive.


MOLLY: And so this one male and this harem of females will basically spend their entire lives on this one patch of reef.


BOB WARNER: Where they mate every day.


MOLLY: Each female with that one male.


MARSHALL PHILLIPS: All that entails is the male and the female will dart up in the water column together ...


MOLLY: And then at the same time, he'll release his sperm and she'll release her eggs.


MARSHALL PHILLIPS: And then they dart right back down.


MOLLY: And then a different female, same male go up. Egg-sperm.


MARSHALL PHILLIPS: And dart back down.


MOLLY: And then again, different female, same male. They go up.




MOLLY: And this is what they do every day.




MOLLY: Kind of sounds like a cult of the 1960s. [laughs]


MOLLY: But say something happens to this male.


MARSHALL PHILLIPS: Well, say a predator comes along and he chomps that male.


MOLLY: So the alpha male ...


BOB WARNER: Is eaten up.


MOLLY: Dead.




MOLLY: Gone. Now the question is: what happens to the ladies? You'd think it would be chaos because their whole system's been thrown out of whack.


MARSHALL PHILLIPS: But within minutes to hours ...


MOLLY: Life finds a way. Somehow, the ladies pick who will be the next male.


BOB WARNER: The ladies have it pretty well worked out who's the largest.


MOLLY: Do they all start, like, eyeballing each other, like ...?


MARSHALL PHILLIPS: They don't line up or anything.


MOLLY: Okay.


MARSHALL PHILLIPS: "Hmm. Am I bigger than you?" No. Like, but somehow they figure it out.


MOLLY: And so once they establish who the largest female is, she starts to change her behavior. She gets a little more friendly ...


BOB WARNER: Towards the other females.


MOLLY: She'll swim up to them.


MARSHALL PHILLIPS: Do this little wiggly dance.


MOLLY: Sort of waving her pectoral fin at the ladies.


MARSHALL PHILLIPS: Which isn't really something they do as a female, ever.


MOLLY: And then ...


MARSHALL PHILLIPS: As time goes on ...


MOLLY: Her body starts to change.


MARSHALL PHILLIPS: She will get a little bit bigger.


MOLLY: How do you just suddenly get bigger?




MOLLY: Her brain starts sending signals to produce tons of testosterone.


MARSHALL PHILLIPS: Testosterone is taking over.


MOLLY: And as she starts to grow ...


MARSHALL PHILLIPS: A little bit of blue starts to appear right at her nose.


MOLLY: Her scales start to change color.


MARSHALL PHILLIPS: And sort of spread backwards right at her chin and spread outwards.


MOLLY: Until her head is entirely blue. And then these dark stripes start to form.


MARSHALL PHILLIPS: Those will eventually become that black-white-black Oreo.


MOLLY: And the other thing that starts to happen is her ovaries start to disintegrate.


BOB WARNER: These are the most valuable cells in the body, and now suddenly they're being destroyed.


MOLLY: And then they start to rebuild themselves into testes that start producing ...


BOB WARNER: Sperm. Really rapidly.


JAD: Wow!


MOLLY: It's nuts. It's absolutely incredible. And then sex cult is back.


BOB WARNER: There's a new dominant male at the top of the heap.


MOLLY: But ...


MARSHALL PHILLIPS: At first, he's not very good at being a male. [laughs]


MOLLY: Like, he doesn't quite know when to dart up and when to spawn.


MARSHALL PHILLIPS: It's just like a teenager who doesn't know how to talk to girls.


MOLLY: But eventually he gets the hang of it.


MARSHALL PHILLIPS: And can produce baby blueheads.


MOLLY: And the cycle of life continues!


JAD: [laughs] That's a good Attenborough.


MOLLY: Thank you.


JAD: That is crazy that they just disintegrate their insides and then rebuild.


MOLLY: But the funny thing is if you ask Bob about this stuff ...


BOB WARNER: No, in fact ...


MOLLY: About how these little lady fish completely transform, he's like "Meh."


BOB WARNER: Yeah, I hate to admit that, but yeah.


MOLLY: It's not that shocking.


BOB WARNER: The shocking thing is how many fishes change sex.


MOLLY: It turns out it's a lot of fishes.


BOB WARNER: Nearly all the wrasses.


MOLLY: Your blueheads, your fairies, your flashers.


BOB WARNER: Parrotfishes.


MOLLY: They actually look like parrots.


BOB WARNER: They change sex. Most of the big groupers.


MOLLY: The tiny gobies.


BOB WARNER: Damselfishes. Everyone asks about clownfish.


MOLLY: Finding Nemo.


BOB WARNER: Yes, they change sex.


MOLLY: But they do it a little differently.


BOB WARNER: They go from male to female.


MOLLY: Up with the clownfish matriarchy. Bob says we're dealing with, like ...


BOB WARNER: Hundreds.


MOLLY: A whole lot of sex-changing fish.




JAD: Wow, hundreds!




MOLLY: But here's a really crazy thing. It's not just fishes.


BOB WARNER: Some shrimps, worms ...


BLANCHE CAPEL: Alligators.


MOLLY: If you include all of the animals in which their sex goes a different way than you would think ...


BLANCHE CAPEL: Flies, lobsters.


MOLLY: Bananas.


BLANCHE CAPEL: Lizards, birds.


MOLLY: Mussels, snails, slugs.




JAD: Chickens?


MOLLY: Oh, eels.


BLANCHE CAPEL: Frogs. It's just amazing. And wait 'til we get to turtles.


MOLLY: It's a whole zoo in this conversation.




MOLLY: So why would fish -- like, why would -- or why would any animal did change sex?


BOB WARNER: Well, I think sex change increases your fitness. You have more young, either eggs that you produce or eggs that you fertilized, than you would as a -- as a single sex.


MOLLY: In other words, it just ensures that you can pass on your genetic material. Like, if you're the fishes on the reef and the male disappears, you're stuck and there's no -- your DNA goes nowhere. But if you can become a male ...


JAD: Hmm.


MOLLY: You can make sure that your DNA goes somewhere, and then, like, all the other fishes in your little kingdom go somewhere.


JAD: Okay, so now let me ask you the next obvious question. You've told me that we come from the fish.




JAD: They've got this flexy-sexy thing, and that we have it to some degree.


MOLLY: Mm-hmm.


JAD: Daniel lurks within you, and is being actively suppress every single day. So can we be like the fish?


MOLLY: Yeah, it does make you think of that. Zarkower says that ever since he did those mouse experiments, he gets this question a lot.


DAVID ZARKOWER: Yeah, yeah. There's some interest from the transgender community and whether this could be something that would be helpful. But we can't do it. We technically can't ...


MOLLY: Zarkower says it's unethical and at this point probably even technically impossible to take that gene away. And even if we could, removing a gene just won't physically reorganize us in the way the fish do. He says at most ...


DAVID ZARKOWER: You might be able to produce your own natural sex hormones of the type that's more aligned with your gender identity.


MOLLY: Oh, pretty crazy you could even get the body to do that. But the reason we can't actually do the full-on switch is because humans -- male and female humans -- have developed internal reproductive plumbing that is so different from each other, it would be impossible at the drop of a hat to switch.


JAD: Well, so then -- then this makes me confused.


MOLLY: Well ...


JAD: Is this, to use Blanche's word from a few episodes ago, is this bi-potentiality that's still is there?


MOLLY: Yeah.


JAD: Latent. Being suppressed. Is that a legacy thing that is just fading away? Or is there -- is it there for a reason? It's there for a reason in the fish. Is it there for a reason in us?


MOLLY: Does it serve a purpose?


JAD: And therefore will be there with us ...


MOLLY: Always.


JAD: Always.


MOLLY: Or maybe even get stronger?


JAD: Yeah, it's ...


MOLLY: No, I asked Blanche that.


BLANCHE CAPEL: I don't know. I don't know. I don't have a good answer for that. But it ...


MOLLY: Do you think anyone does? Or is this like a ...


BLANCHE CAPEL: No, I don't think anyone does. I think we're all trying to figure out why it would be the case. And most people ask the same question you asked: why would this be true? And I don't know why it would be true.


MOLLY: Even if we don't know why, just knowing that that other path is there just below the surface, you know, almost like wanting to express itself, does make you think a different way about how rigidly we define ourselves.


BLANCHE CAPEL: I think we like to bend people as male or female and we have always put people in two piles. But I think there's a tremendous amount of middle ground. Even when you're just talking about, you know, things like the level of testosterone you're making or the level of estrogen you're making, or the shape of your genitalia, or many other features that we bend as male or female. I think there is a lot of -- there's a lot of variation between the two piles. And maybe we just haven't appreciated the variation that exists naturally in our population.




MOLLY: This episode is reported by me, Molly Webster, and produced by Matt Kielty with additional production help by Rachael Cusick. Pat Walters was our editor. Scoring, mixing and original music by Alex Overington and Matt Kielty. The Gonads Theme and The Ballad of Daniel Webster were written, performed and produced by Majel Connery and Alex Overington. Special thanks for this episode go to Erica Todd, Andrew Sinclair, Robin Levelbatch and Sarah Richardson. Thank you to composer Erik Friedlander for allowing us to use his work Frail As A Breeze Part 2 and musician Sam Prekop, whose work A Geometric from his album The Republic is out on Thrill Jockey. I think you should sign up for the Radiolab newsletter. You might think, "A newsletter? What's the big deal? Everyone's got one. But in our newsletter, you're gonna get a bunch of staff picks telling you about super cool things we discovered while reporting this series. Sign up at Radiolab.org/newsletter or text gonads to 2701-01.


MOLLY: Radiolab Presents: Gonads is Rachael Cusick, Pat Walters, Jad Abumrad, and me, Molly Webster. See you next time.


[ANNETTE: Hi, it's Annette Udall calling from Newcastle, California. Radiolab was created by Jad Abumrad and is produced by Soren Wheeler. Dylan Keefe is our Director of Sound Design. Maria Matasar-Padilla is our Managing Director. Our staff includes Simon Adler, Maggie Bartolomeo, Becca Bressler, Rachael Cusick, David Gebel, Bethel Habte, Tracie Hunte, Matt Kielty, Robert Krulwich, Annie McEwen, Latif Nasser, Malissa O'Donnell, Arianne Wack, Pat Walters and Molly Webster. With help from Shima Oliaee, Carter Hodge and Liza Yeager. Our fact-checker is Michelle Harris. How'd I do, guys?]