Radiolab - Gonads: The Primordial Journey

Episode Date: June 15, 2018

At two weeks old, the human embryo has only just begun its months-long journey to become a baby. The embryo is tiny, still invisible to the naked eye. But inside it, an epic struggle plays out, as a nomadic band of cells marches toward a mysterious destiny, with the future of humanity resting on their microscopic shoulders. If you happened to have caught this show on air, you can find the second half of our broadcast version here.  This episode was reported by Molly Webster, and produced by Jad Abumrad. With scoring and original composition by Alex Overington and Dylan Keefe. Additional production by Rachael Cusick, and editing by Pat Walters. The “Ballad of the Fish” and “Gonads” was composed and sung by Majel Connery, and produced by Alex Overington. Special thanks to Ruth Lehmann and Dagmar Wilhelm. 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. Support Radiolab today at Radiolab.org/donate.

Hi, I'm Robert Crulwich. Radio Lab is supported by Casper. As we begin this episode on reproduction in the human body, check out the Casper or The Wave Mattress, providing supportive comfort for all kinds of bodies. Visit casper.com slash radio lab and use code radio lab at checkout to get $50 towards select mattresses. Terms and conditions apply. Hi, I'm Robert Crulwich. Radio Lab is supported by Audible. As we begin this episode on reproduction and development, check out. how we do it, the evolution and future of human reproduction. Go to audible.com slash radio lab or text RadioLab to 500-500 for a free 30-day trial and a free audio book. Wait, you're listening.

Okay. All right. You're listening to Radio Lab. Radio Lab. From W-N-Y-S. C. See? Yeah.

Hey, this is Chad. to present to you guys starting today here on Radio Lab, a mini-series from producer Molly Webster. It's been my goal as a fish. It's been my goal. For so long I've waited till before, I've waited to carry you, all of you, all of you, all of you. Hi, I'm Molly Webster. I'm so full of eyes. For the last. I have so many years. I don't know.

I'd say three years. It's too much for me. I've been doing a lot of reporting about how humans make more of themselves, right? Like science stories, ethical stories. And we came up with this idea that. you know, rather than me reporting only on reproduction for the next 10 years at Radio Lab, that what if we just put them all together in a series? And so we're about to do that.

For the next month, we're going to do this series. And the name of the series is gonads. I know what you're thinking. Why? I'm going to ask you a question. You can say no. What do you think about the word gonads? Go. Gonas.

Oh. That's a crazy question. It's almost like that word moist, where it gives you like a little, uh-huh. Yes, that word does have certain connotations. What do you think of? Bonnet, isn't that nuts? It's a slang term for balls. Balls. Testicles.

Testicles. Balls. Definitely balls. You got guajon. It's just used in like stupid boy humor. So almost like toxic masculinity situation. You just think like sweaty balls and male jokes pretty much. Like kick you in the nads?

Great. Would you think it has anything to do with ladies? No. No. No. Oh, no. Did you know that ladies actually have gonads also? That gonads are both testes and ovaries? Oh, really?

That it's actually for men and women. Really? I did not know that. I did not know that. Did not know that. 90% of the people I talked to. Didn't know that. They didn't know it.

Who would have thought? Women and men both have gonads. Culture, they've stolen the word and made it male. And I think it's time we reclaim this word. Like, as a citizen, as a human, as a lady, as a science lover. I'm taking the word back. Okay, so this is episode one. And this whole series, like, kind of came into being with a single phrase. All right.

The duck is in the house. From this guy. Can you say for me your name and how? how you identify yourself. I'm Kutlokhti. I am an ovarian biologist. So I have a research laboratory at Yale University School of Medicine. So Octet, he is the one who said the gonads are magical organs.

They are. Gondads are magical organs. So Octet is Turkish? You know, I... was a curious kid. He grew up in Istanbul. I was a Treki as a child. And as I was 10 years old, I would you know, you know, look into the universe in the skies and trying to understand, you know, make sense of this whole thing. What was it about the sky that attracted you? It was the concept of infinity. You know, we're just living a mundane life on this planet without thinking of

anything but our routine concerns. But at the same time, we've got this vast space around us, and most of we have no clue. We live oblivious to that fact. And I would lose sleep over that when I was a kid. Really? Yeah. Fast forward, Octet goes to medical school in Turkey. He becomes a doctor, specifically an OBGYN. So I had to do over a lot of babies, probably 20,000 or so. Wow. That's like birth. a small town. And then, you know, after having made 20,000 delivery, I said, you know, perhaps this is not my calling. I wanted to be a little bit more, more towards the beginning of the process. You know, when you're an obstetrician, you're dealing with the finished product, right?

Well, I just think that's a crazy statement because most people think babies are the very beginning of the process. I'm not sure what gets more beginning than like a small baby. Popping out of a lady. That feels like the starting line. started something. But in Octay's case, there was like some sense that most of the decisions, most of something had already been decided by the time the baby gets out. And that whole process is fascinating. So we dragged him into the studio to talk about magical gonads, basically just to figure out why are they magical? I'm interested how you settled on that word. Yeah, what did I say? You know, I think magical for many reasons. One is their origin. You know, they...

And he told me what he learned when he started studying this stuff, was that the origin of the gonad, like its creation is sort of the beginning because it starts with this whole saga that is so involved and so extreme that the baby itself does kind of feel like an afterthought. He calls it. The Great Migration. The Great Migration. Octet got me into this story, and so I ended up calling a bunch of people about it.

In my lab, we have a slogan that says, go nads or go home. We have t-shirts. You don't. You do? We do. We have a t-shirt. That is Blanche Capel. Professor in cell biology at Duke University Medical Center.

She essentially studies all the parts of the story we're about to tell you. Okay. So, to place this story in time, it begins at about, oh, two or three weeks in humans, I bet. Let's say day 24, just to be safe, which basically means a sperm fertilized an egg 23 days ago. It could be a petri dish. be sex, who knows. But inside this woman's uterus, there's a little organism that has been growing for 24 days. What does the embryo look like at that point? That's my comrade in arms, Pat Walters, who's the editor of the series. Gosh, I don't know how to describe this very well to you.

I could send you a picture. Does it kind of look like a tadpole? Exactly. That's not so wrong. It looks like a tadpole. You know, if you look at a very early embryo, it's like curled up. There's a tail. Got a little tail. There's like the sort of ball of the embryo that's like forming. the developing body, and then it has this like sweep of a tail that's coming off. And if you zoom into the tail, you'll see a little region. It's called the Alentoas. Called the Alentoas. Which is the trash bag of the embryo.

Before the embryo has an excretory system, it dumps things that it doesn't want in the Alentoas. Urine, it flows in and out there. It's where gas exchange with the mother happens. So... Kind of a terrible place. It's like a foreign planet. This isn't actually part of the embryo itself? No, it's sort of in the hinterlands.

The Alenthoas, I always imagined, is where Harrison Ford was camped out in Blade Runner 2049, which is like that vast dust desert. Super orange dust, yeah. And there's like windstorms and like wind blowing over the desert. I imagine it like that. And it's here where you find some cells. These very specialized cells, germ cells, germ cells. The germ cells.

Primordial germ cells. These are the cells that are going to go on that great migration and put the magic in the gonad. They're very interesting cell type. They're set aside very early in embryogenesis. And how many are there? Are there like 1,000? A 1,000?

A 2,000? I think there's something like 40. Wait, that's it? Or, yes. 40, biblical number. And the irony here is, is these cells sort of like huddled at the edges of this wasteland might actually be the most important cells in the body. Because after the embryo grows, after the baby gets born, after that baby goes through puberty,

and one day maybe decides to have a kid, these cells, which are present at the very beginning, these cells are in charge of making a next generation of you. I mean, that's the meaning of life, right? That's the origin of life. These cells, everything else, I mean, we think it's brain, heart, etc. But I think everything else is there to support the survival of the germ cell. They're the stem cell of the species, right? So stem cell means a cell that can create other cells, an originator cell.

We have stem cells for long. stem cells for heart, stem cells for neurons. These cells are the only cells that can make on their own, all the other kind of cells. They can make a whole person. So they have a remarkable underlying pluripotency. Do you think they know that? Well, that's, I mean, those are very difficult questions to answer. I don't know.

I think germ cells know they're really special cells. But I don't think they know what they're going to become. We can ask you a question, if they're so special, why do they start out in the trash? Yeah, that seems like a bad place. You would think. It's very curious that the germ cells arise near that position, and it's unclear why. Or you hide your most precious object in the trash dump. I'm like, this is like got like the best mission impossible, like murder on the Orient Express.

Yep, maybe that's the plan. I don't know. In all seriousness, for some reason, and scientists don't know exactly why, it seems like evolution has this decided to set these cells aside at the beginning of development, which means they have to make a journey back to the middle of the embryo where their destinies will be revealed. And if they make it there, we make it there. If they don't? We don't. Okay.

Okay. So they hang around this dusty wasteland for a few days huddled against the elements. I wonder what that's like for them. I imagine if I was in that situation, I would just be like wondering how this was my lot in life. Is this some sort of cosmic joke? I have a sense I may be important, but I'm just here Don't know why In the wasteland

So they hang out like that for a couple of days And then Do do There's a call They hear a call Maybe smell a call Let's say here There's a signal

They're called into action And so The cells start migrating They literally move Wow what Wait so how does a cell march They actually extend philipodia, which are little cell-like feet. Is it like it pops out two feet and then it goes walking?

Cells send out extensions, and that extension has a little adhesion molecule on it, like a little sticky spot. So when it puts its foot out, it can pull the rest of the cell up to it. So they take a hike, pike, pike, pike. And interestingly, the germ cells seem to be whole. holding hands like a long string of paper dolls. And they touch each other. It's as though they are, the whole crowd is like going together. And after a bit of a hike, they get to the wall of the embryo,

which is like, I don't know, a pulsating mass. And somehow... This is a very blurry period. I have to say. They push their way through the wall. And on the other side, it's just chaos there. It's like a foreign plant.

Because what's happening is, I mean, the embryo is just like dividing, dividing, dividing, dividing, dividing, dividing, dividing. You know, the whole embryo is developing very fast at this stage. Trying to start forming parts, like it wants to form organs, it wants to form a nervous system. There are all kinds of signals flying around to tell the gut to form and to tell the liver to form. Blood cells are popping up, neurons. You know, all these signals are flashing all around. and yet the germ cells, their job is to block it all out. They migrate right down the middle of the embryo at the midline.

Almost like where you could think like a spine would be. Through a forest of signals going around in the embryo. And these signals are bombarding them. Trying to tempt them. Like, hey, be a liver cell. Be a liver cell. Come be a liver. Be a liver.

And sometimes these cells are like, hmm. Hmm, wait. Do I want to be a liver? Am I a liver? No, wait, something tells me as you keep marching. It seems scary, doesn't it? Yeah. Yeah, they go through a battle. Hey, do you know if they ever lose one along the way?

Like, the chain is going, and they're trying to, like, don't differentiate, don't differentiate. Does, like, the fourth one from the end ever go, like, phew? And just become a stomach. And they're like, oh, crap. We lost Stan. Keep going. Hurry, hurry, hurry! It probably happens.

But they try to stay focused together, and they try to resist all of those signals that could divert them from their destiny. They want to stay uncommitted. These might be the last cells in the developing mammalian embryo to give up their world of possibilities. This is David Page.

He is the director of the Whitehead Institute, biologist at MIT. If you see what I'm saying. So basically, when an egg is fertilized by a sperm, to go back to that beginning, the resulting cell called a zygote, the fertilized egg, has the possibility, has the potential to become every type of cell in the body. And as one cell becomes two and two become four and so on and so on, eventually some cells give up that broad range of possibilities and become committed to narrower, occupations and specializations. You know, we have at least 200 or 300 specialized cell types that make up our body. All the other cells make the transition from possibility to reality.

And those migrating primordial germ cells are the last cells to give up a wide range of possibilities. Oh, I like that for their like pugnaciousness. Yes, yes. Okay, so getting back to the band of 40, we're back in the thick of things. They're marching through the middle of the embryo, being like pelted and torn at, fighting off all these other signals. And they do this for one day, two days, three days, four, five. I imagine they get tired as they go.

Six, seven, eight. But the signal that they're following is getting stronger. And then pretty soon over the horizon, on kind of either side of the path, they start to see these mountains. The Eurogenital Ridge is going to emerge as sort of a mountain off the back wall of the body cavity. So they're still marching down this path. They're following the signal. The mountains are getting closer and closer. and then at some point the path in front of them splits.

It goes to the left and it goes to the right. And half the cells will go to the left and half the cells will go to the right. Regardless of what direction they go in, they end up at the base of a mountain. And the mountain is a mass of, like a dense mass of cells. And they come right up to the edge of the mountain wall and they're able to just like push those cells aside.

and like squeeze into the interior of the mountain, which is an entirely new space. So the germ cells enter. Enter the gonad. Oh, this is the gonad? Yeah, this is the place that will either be an ovary or a testes. And which, I mean, has it been figured out which it is? No.

At this point, it could go either way. I think about this place as a cathedral. And the cathedral, it's sort of under construction. And as they walk in, they probably know immediately that this is the place that's been calling them because that signal that they've been following. It's everywhere. Maybe when they get to the gonad, the whole cell is surrounded by the signal, and that tells the cell to stop. But this is just a guess. What do you think it's like for the germ cells?

Like sort of they've been going on this walk, and then they get to a place that says, stay here. So I wonder what the stay here like, I don't know, feels. like, oh, I think it feels like home. After marching for almost two solid weeks, they finally arrive. They recognize this is where they belong. But everyone I talked to said

probably still at this point. They don't even know what lies ahead for them. Or even why they're there. We're anthropomorphizing, but why not? David Page again. I would suggest that the primordial germ cells, they have been instructed to migrate

to the genital ridge. But they don't know why. And they don't know what they're going to do when they get there. They have not a clue. But the clue is coming. This is Jeff Pearson calling from Grand Island, Nebraska. Radio Lab presents GONADS is supported in part by Science Sandbox,

a Simon Foundation initiative dedicated to engaging everyone with the process of science. Additional support for Radio Lab is provided. by the Alfred P. Sloan Foundation. Hi, I'm Robert Crilwich. Radio Lab is supported by Casper. As we continue listening to this GONADS episode on Reproduction and the Human Body,

check out the Casper mattress with zone support for your hips and shoulders for better alignment or the wave, which mirrors the natural shape of your body. You can be sure of your purchase with Casper's 100-night, risk-free sleep-on-a-trial.

Right now, get $50 towards select mattresses by visiting casper.com slash radio lab and using code Radio Lab at checkout, terms and conditions apply. Hi, I'm Robert Crulwich. Radio Lab is supported by Audible. As we continue this GONADS episode on Reproduction and Development,

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Okay, so to pick up on the action, the tribe of 40, they find themselves in a cathedral-like space, technical name. The mezzanephyric, gonadal region. I'll call it the House of Gonad. They're in this beautiful space. But they don't know why. But what happens is, immediately, when they enter, they are surrounded by somatic cells. I imagine these cells as like friendly monks just gliding around in red robes.

Their job is to just protect you and make sure that nothing bad happens to you. These are the cells that have been calling them? I don't know. That's kind of a hard question to answer because the genital ridge had just started forming when the germ cells began their migration, so no one really knows what was sending the signal. But after a few days, some people say a few weeks, these somatic cells that are gathered around the germ cells will lean in real close. And they reveal the destiny. They tell them either one of two things.

You will become a sperm or you will become an egg. What exactly are these monk cells doing, though? I mean, to make them change, are they, like, bumping them in some special way? No, no, no, no, they're releasing proteins. Well, there are molecular signaling cascades that are controlling the male or female fate of the germ cells. And what makes them go one way or the other? Ugh. That is super complicated, and we're going to get into it later in the series.

So for now, I'll just say. In mammals, sex is genetically controlled by whether or not you have two X chromosomes or an X and a Y chromosome. So it's just basically like your fourth grade biology of the, the cells in the cathedral have a Y chromosome, they'll say sperm, and if the cells in cathedral have an X, X chromosome, they'll say egg. So it's still basically just fate and luck as to which way they go? Yes, but here's the cool part. If the monks tell the germ cells that they're going to be sperm, they basically divide a little

bit, and then the monks take the germ cells and they put them to sleep. They sort of, I don't know, entombed them in these, like, catacombs until, uh, after birth and puberty. But if the germ cells get told that they're going to be eggs, something different happens inside of them, and they just go nuts. They divide. They divide quite a lot, rapidly for a while.

Suddenly the band of 40 becomes thousand, and 2,000, and 10,000. The monks then take each of these new eggs and embed them in the wall of the cathedral. Divide, boom, divide, boom, Divide, boom, divide, boom. They literally shove the eggs into the wall of the House of Gona? Yes.

And this goes on for months. As a matter of fact, their numbers probably reach around 6 to 10 million during the fifth month of pregnancy, about 20 weeks of gestation. That embryonic ovary is going to have all the eggs it will ever have when it's only five months along. Wait, this is all still in utero? This is all in utero it's happening. It has 10 million eggs. and it is still itself months away from being born? Yes.

Theoretically, at that point, that is 500 times more babies than Octet ever delivered in his career in this one developing embryo. Fuck. Yeah, I know. God, you know what just occurred to me? If you go all the way back to the beginning of this story, you told, Day 24 or whatever it was, you've got this little organism forming. Probably the mother doesn't even know it's there yet. But already there are these cells in existence that will be the kid of the kid. She doesn't even know she has yet.

So her grandkids are in there already? Is that right? So when you're pregnant with a person, you carry inside of you the cells that will make the next. Oh, you're right. It is granddaughter. It's like your grandkids are already inside of you. Inside of your unborn child. Yes.

That's bananas. Yes. Do you think the great grandkids are in there, too? Well, it's like all this. That's what she means by stem cell of the species. Because it's the same material that makes, they then, they not only make the body, they make more eggs and sperm. They make the next generation of egg and sperm. So they're both making a generation, but then making the ability for that generation to make another generation.

Oh, my God. This is like. So it is like humanity. It's mirrors. You're not only cradling like your child. You're cradling like infinite future homo sapiens. Wow. That's the infinity.

It's crazy that all that is there and you're not even a thing yet. That the first thought or thought, I don't know, the first thing that this organism has been programmed to do is not, hey, make a person, make a brain, make a life. No, it's make more. Yeah. It's pretty gnarly. Yeah. You know, many, many people believe that we. exist just as a harbor for our germ cells until we can make new people. Like, we're just their

hosts. In some sense, that's absolutely true. I mean, or as was said a long time ago, a chicken is an egg's way of making another egg. Really? I've never heard that before. So I was in Michigan a couple of weeks, months ago. And so I was in Michigan and I was kayaking on this river that has super sandy bottom and it's like pretty shallow. I don't know. It's like three or four feet deep. And the cool thing was that the salmon were spawning. Huge fish. They were like three to four feet. They were so thick around and there were so many of them that they would like rustle my kayak. And I see something kind of in this one part of the river like by itself. And I look and it's a fish. It's a salmon that's lying.

on the bottom of the river. And I see, like, through the ripply water, some, like, pink. So I turned the kayak around to go, like, look at it. And what I realize is the pink is not, like, flesh. The pink is, like, packed eggs. The body was sliced open so you could see into the hollow. And in the hollow were just, like, what felt like millions of these, like, bubble gum pink drops of eggs.

like the entire body cavity was packed eggs. And to think that parts of our body, male and female, by the way, because the testes do this just a little later in life, to think that parts of our body are like that fish, it felt like just pulling back the curtain and seeing something that I can never unsee. This episode was reported. by me, Molly Webster and produced by Jad Abumrod, original music by Dylan Keefe, Ballad of the Fish and the GONADS theme were written performed and produced by Majel Connery and Alex Overrington. Radio Lab presents GoNads is produced by Rachel Cusick and edited by Pat Walters.

One last thing before I go. Later in the series, we're going to dig into Sex Ed. And one of the things that comes up in every conversation you have about Sex Ed is a book that somebody read to learn about. the birds and the bees. It might have been given to them or they found it like in their library book sale. So we want to try and create an online sex ed library with as many of these books as we can find for all ages. So go to radio lab.org slash sex ed books and tell us about a book you got as a kid and the reason you loved it or didn't. And then we're going to add it to the chef and it's going to be great.

So that's it. That's our episode and see you next time. Bye. It's created by Chad at Evermondaud and it's produced by Soren Wheeler. Dylan Keith is our director of sound design. Maria Matasar Padilla is our managing director. Our staff includes Simon Adler, Maggie Rottalmo, Becca Bressler, Rachel Cusick, David Gebel, Bessel Hapty, Tracy Hunt, Matt Kielty,

Robert Crullwich, Annie McEwen, Latif Nasser, Melissa O'Donnell, Adrian Wack, Pat Walters and Molly Woodster with help from Shima Alii Carter Hodge and Liza Yeager. Our fact checker is Michelle Harris. Hi, I'm Robert Crulwich. Radio Lab is supported by Casper.

Check out The Casper or The Wave mattress with a support system that mirrors your body shape. Get $50 towards select mattresses by visiting casper.com slash radio lab and using Code Radio Lab at checkout. Terms and conditions apply. Hi, I'm Robert Crulwich. Radio Lab is supported by Audible.

Check out how we do it, the evolution and future of human reproduction. Go to audible.com slash radio lab or text Radio Lab to 500,000 for a free 30-day trial and a free audio book.