Aug 26, 2021

The Unsilencing

Multiple sclerosis, lupus, rheumatoid arthritis, even psoriasis — these are diseases in which the body begins to attack itself, and they all have one thing in common: they affect women more than men. Most autoimmune disorders do. And not just by a little bit, often by a lot; in some cases, as much as sixteen times more. But why? On today’s episode, we talk to scientists trying to answer that question. We go back 100 million years, to when our placenta first evolved and consider how it might have shaped our immune system. We dive deep into the genome, to stare at one of the most famous chromosomes: the X. And we also try to unravel a mystery — why is it that for some females, autoimmune disorders seemingly disappear during pregnancy?

This episode was reported by Molly Webster, and produced by Sindhu Gnanasambandan and Molly Webster. The Gonads theme song was written, performed, and produced by Majel Connery and Alex Overington. 

Looking for something else to listen to? We suggest pairing “The Unsilencing” with “Everybody’s Got One,” an episode about an unknown super-organ that nobody on the planet would be here without: the placenta.

Want to learn more? You can …
...check out a Montserrat Anguera XX study,
...read Melissa Wilson’s placental, pregnancy hypothesis,
…and get a primer on Rhonda Voskuhl’s estriol & Multiple Sclerosis work.

 

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(SOUNDBITE OF MUSIC)

MELISSA WILSON: Could I ask when this might air?

MOLLY WEBSTER: Yeah.

MELISSA WILSON: I'm four months pregnant today.

MOLLY WEBSTER: Congratulations.

MELISSA WILSON: And I just got a - yeah, no, it's super exciting. And I was diagnosed with Hashimoto's six months ago. So it was just like...

MOLLY WEBSTER: Wait. Is Hashimoto's an autoimmune disorder?

MELISSA WILSON: It is.

MOLLY WEBSTER: I'm Molly Webster.

LULU MILLER: And I'm Lulu Miller. This is RADIOLAB.

MOLLY WEBSTER: And today, we are looking into one of the biggest medical mysteries, which is why a body sometimes turns on itself.

LULU MILLER: And, Molls, you're going to lead us through this one.

MOLLY WEBSTER: Yeah. And it's something I got pulled into when I first was working on gonads.

UNIDENTIFIED PERSON: Gonads.

LULU MILLER: Gonads...

UNIDENTIFIED PERSON: (Singing) Gonads. Gonads. Gonads.

LULU MILLER: ...For anyone who hasn't listened is the romp through sex-freaking-ed you didn't know you didn't know. What was the actual tagline?

MOLLY WEBSTER: The parts of us that make more of us.

LULU MILLER: The parts of us that make more of us. That's good.

MOLLY WEBSTER: So gonads was all about, like, sex development, right?

LULU MILLER: Right.

MOLLY WEBSTER: So I was, like, deep in X’s and Y’s and when do we kind of divide off on these paths that are called, you know, gender in, like, the top-level world. And while I was in that space, one of the things that came up was that there are sex differences in how we get diseases.

LULU MILLER: OK.

MOLLY WEBSTER: And one of the places this is, like, very apparent is in autoimmune disorders. It's very puzzling.

MELISSA WILSON: Why does autoimmune disease occur eight times more often in women than men?

MOLLY WEBSTER: Is it that big of a difference?

MELISSA WILSON: For rheumatoid arthritis it is, yeah.

MOLLY WEBSTER: Wow.

RHONDA VOSKUHL: And of course, in MS, it's two-thirds to three-fourths.

MONTSERRAT ANGUERA: Hashimoto's disease - 95% are women.

MOLLY WEBSTER: That's like almost the entire case study.

MONTSERRAT ANGUERA: Yeah. Isn't that crazy?

LULU MILLER: Wow.

MOLLY WEBSTER: So I just - I fell into this, like, series of conversations with, interestingly, like, very provocative women scientists who are, like, trying to answer this. And we're going to circle back to each of them. But first, a little basics in autoimmune disorders. Your immune system - it starts attacking you. And there's, like, various ways it can do that. It can be anything from you have skin rashes to patchy skin to infertility to - you have neurodegenerative, like, MS, like, breaks down your brain and your nerves, so you end up having trouble walking and cognition. Some of them, you die earlier from. Some of them, you know, are just, like, an itchy patch on your skin. So it really is the gamut. And honestly, on top of all this, it seems like incidences of autoimmune disorders are going up. And so you have this real question of, like - why?

LULU MILLER: Yeah.

MOLLY WEBSTER: Like, what's happening here? So this has to be genetics. This has to be at the genetics. And so, Lulu Miller, we are going on a journey.

LULU MILLER: OK.

MOLLY WEBSTER: Go to the bathroom now. We have three stops to get through. Starting with...

MONTSERRAT ANGUERA: Montserrat Anguera.

MOLLY WEBSTER: An immunologist.

MONTSERRAT ANGUERA: And I'm at the University of Pennsylvania.

MOLLY WEBSTER: And her way into this mess is by looking at one of the most well-known chromosomes.

MONTSERRAT ANGUERA: I'm absolutely fascinated by the X chromosome. I love this chromosome. And - (laughter) sounds so silly, doesn't it (laughter)?

MOLLY WEBSTER: No. And while we all know this chromosome for sex, Montserrat knows it for this other thing.

MONTSERRAT ANGUERA: The X chromosome has the highest density of immune-related genes of all the chromosomes.

LULU MILLER: Oh, my gosh.

MOLLY WEBSTER: And so now this is interesting because everyone on the planet has one X. But typical females have two. And so Montserrat wondered - like, could there be something going on with this extra X packed with all of these immunity genes that's leading females to get autoimmune disorders more?

MONTSERRAT ANGUERA: Exactly. Exactly.

MOLLY WEBSTER: Now traditional wisdom is that if you have a second X or a third or a fourth, it will get turned off or something called silenced.

MONTSERRAT ANGUERA: Fifty percent of the cells are going to silence mom's X. The other 50% are going to silence dad's X.

MOLLY WEBSTER: And the way it does this is actually a really physical process because wrapped around any extra X are these long strands of RNA.

MONTSERRAT ANGUERA: We can look using a microscope at the nucleus of a cell. And we can use probes that are specific for the long noncoding RNA, and we can light them up in pink. And what we see is that RNA will form this beautiful cotton candy cloud structure that completely envelops the inactive X chromosome.

MOLLY WEBSTER: Wow. So it's, like, muzzled.

MONTSERRAT ANGUERA: Yeah. It's like, yeah, swaddled.

MOLLY WEBSTER: Swaddled.

MONTSERRAT ANGUERA: It's absolutely beautiful.

MOLLY WEBSTER: Beautiful. And scientists assumed durable. The thought was - is that once an X was silenced and this starts in an embryo, it would stay silent.

MONTSERRAT ANGUERA: Absolutely.

MOLLY WEBSTER: And not just that, experiments have shown that in cells where this doesn't happen...

MONTSERRAT ANGUERA: The cell will just start to, like, die.

MOLLY WEBSTER: So Montserrat was like OK I'm just going to take a look at this extra X and see what's going on.

MONTSERRAT ANGUERA: So in lupus, 85% of patients are women.

MOLLY WEBSTER: And so she looked inside cells - immune cells of people with lupus. And what she saw...

MONTSERRAT ANGUERA: No cotton candy cloud. Instead of being the fluffy cotton candy on the inactive X chromosome, they had dispersed patterns of RNA.

MOLLY WEBSTER: When she looked inside, she saw little pinpoints of hot pink all over the nucleus.

LULU MILLER: Whoa.

MOLLY WEBSTER: So it's not muzzling. It's, like, shredded - it's like - it's just all around.

MONTSERRAT ANGUERA: Right.

MOLLY WEBSTER: OK. And so it's like - what does this mean? What Montserrat is thinking is that maybe this X being unsilenced is allowing extra immune genes to turn on, which is throwing the immune system into, like, this turbo charge. And that could be contributing to autoimmune disorders.

LULU MILLER: So she's saying more X’s able to unsilence means more genes firing off?

MOLLY WEBSTER: Yeah. Obviously, there's a ton more research to do. And this is just a working hypothesis, but there's one more piece to this, which is that as she was seeing these X’s become unsilenced, she was just like - you know what? I'm going to poke around in the cells of healthy folks, too, in, like, their immune cells. And she found that in those cells, also, X can sometimes get unsilenced.

LULU MILLER: So is that, like, a prewarning sign that they might be about to get sick?

MOLLY WEBSTER: Not necessarily because, like, 30,000 things contribute to autoimmune disorders. But it might account for this other pretty rad sex difference you see in humans.

LULU MILLER: OK.

MOLLY WEBSTER: Which is that if you just look at, like, stereotypical females and males who are healthy, on the baseline, females have stronger immune systems than males.

LULU MILLER: OK. So you are sitting next to Soren. You're - like, you're on guard. You're ready to fight. I mean, does that then - does that reflect in those disparities? Like, do men have more, like, thing - like, I don't know viruses.

MOLLY WEBSTER: Well, yeah, yeah, yeah, yeah. Well, this is why the COVID numbers are so skewed, right? The guys have three times greater likelihood of going into the ICU and they have a greater chance of dying than women.

LULU MILLER: Is that why? I mean, it's not - like, lifestyle part of it really may be a part of the puzzle might...

MOLLY WEBSTER: Part of the puzzle of why is just that, like, women have stronger immune systems that do stronger initial responses and so can often fight back viruses or bacteria better.

LULU MILLER: Do people know this? Like, is this - that's so - I - that's so cool. Like, women just run...

MOLLY WEBSTER: I know. This is what I'm - yeah.

LULU MILLER: ...Around with better immune systems all the time?

MOLLY WEBSTER: On any given day, a female walking around on the street is ready to fight off a pathogen in a way that, like, men aren't.

LULU MILLER: (Laughter) It's just - I'm picturing like...

MOLLY WEBSTER: Yeah.

LULU MILLER: ...Spears, like, (imitating throwing spears). Like, we just got this whole army, that men are, like - like, their warriors are like...

MOLLY WEBSTER: Yeah.

LULU MILLER: ...Filing their toenails and like...

MOLLY WEBSTER: Yeah. And you're like, this is such a crazy cool super power.

LULU MILLER: Yeah.

MOLLY WEBSTER: And then I have this, like, one moment where I'm like, I will get less flu, but I may get rheumatoid arthritis.

LULU MILLER: Right.

MOLLY WEBSTER: Like, so there's, like, this...

LULU MILLER: Right. There's always the whole evolution tradeoff thing. You can't just get a gift it seems.

MOLLY WEBSTER: That is true. It is very hard to be excited about the super power if you are worried about the back end of it. I'm just going to think about my little toxic X’s inside of me.

LULU MILLER: They're a little ticking time bomb, yeah.

MOLLY WEBSTER: (Laughter) I don't know why I'm giggling.

LULU MILLER: So - (laughter).

MOLLY WEBSTER: That just is not what I expected. It struck me as funny. OK.

LULU MILLER: Yeah.

(SOUNDBITE OF TICKING CLOCK)

LULU MILLER: When RADIOLAB comes back, we are going to learn how the heck we got here and a possible way out.

Molly.

MOLLY WEBSTER: Yes, Lulu. Hi.

LULU MILLER: Hi. This is RADIOLAB. We are back from a quick break. Today, we are talking about - what are we talking about, Webster? We are talking about why it is beautiful and terrible to be a person with two or more X chromosomes.

MOLLY WEBSTER: Yeah.

LULU MILLER: Because on one hand, like, maybe you're a little bit better at fighting off viruses. But that same immune system can also turn on you. So I do think sometimes this just happens. There's accidents. There's imperfect innovations in evolution. But is there any sense of, like, why this might be advantageous, why this might be the case that we are the unfortunately or fortunately chosen ones?

MOLLY WEBSTER: Yeah. There's probably a few different ways into why, but I talked to one scientist who gave a really - I don't know - almost, like, haunting beautiful why.

LULU MILLER: Haunting and beautiful, all right.

MELISSA WILSON: Let's just circle all the way back.

MOLLY WEBSTER: And that's our second scientist.

MELISSA WILSON: Melissa Wilson.

MOLLY WEBSTER: She's a geneticist and...

MELISSA WILSON: Professor at Arizona State University.

MOLLY WEBSTER: And Melissa is taking us all the way back to about a hundred million years ago to when the placenta evolved. And so as you'll remember from our last episode...

LULU MILLER: Recently met and got to know intimately.

MOLLY WEBSTER: We did, so I won't go deep into it here. Y'all should go listen. It's called Everybody's Got One. But what you need to know here...

MELISSA WILSON: The placenta is not the DNA of the pregnant individual.

MOLLY WEBSTER: It's like a foreign object. And so your body naturally wants to fight off something that's not part of it. But the placenta was pretty wily. And it started doing things to essentially get the mother's body to let it stay and to not attack it.

LULU MILLER: Right.

MOLLY WEBSTER: And so one of the things the placenta does is it quiets the mom's immune system.

MELISSA WILSON: The placenta itself is blubbing off signals to downregulate the pregnant person's immune system.

MOLLY WEBSTER: And it's, like, just shushed.

MELISSA WILSON: So the pregnant person's immune system has to say, OK, sure. You know what? We're going to downregulate components of that. That's fine. But you know what? If I downregulate everything, I don't have sanitation. I don't have antibiotics. This is over most of evolutionary history. If I downregulate everything...

MOLLY WEBSTER: Dead.

MELISSA WILSON: ...I will die, right? And so the pregnant person's body has to do this kind of tightrope walk. It has to take those signals from the placenta to downregulate components of it. But it also needs to say - you know what? No, I can't downregulate everything. I have to upregulate some things to be able to not die of parasites and pathogens.

MOLLY WEBSTER: So Melissa's hypothesis is like, while we were all co-evolving - right? - like, the human mammal and our ancestors were starting to get a placenta. And the placenta and the fetus and the human ancestor mammals were all trying to figure out how to live with each other. In this big dance, one of the things that happened was if the placenta is going to drag down the immune system...

LULU MILLER: Yes, right.

MOLLY WEBSTER: ...To shush it, then the mom is going to start evolving an immune system that's actually stronger...

LULU MILLER: To be overexpressed?

MOLLY WEBSTER: Yes, yes, so that when it's dragged down, it's not dragged down to, like, a death level; it's just dragged down to like a moderate level.

LULU MILLER: Oh, wow. Wow. OK. So essentially, it's all the placenta's fault. Like, we double-X’s have to walk around with these amped up immune systems to just survive its presence?

MOLLY WEBSTER: Theoretically, yes. And you actually might be able to see this play out, really, today because in some women who have autoimmune disorders...

MELISSA WILSON: Their symptoms will go away during pregnancy.

MOLLY WEBSTER: They have - (laughter) like, they have symptoms, and then it just goes away?

MELISSA WILSON: People with rheumatoid arthritis who become pregnant - it's as if their autoimmune disease is gone. This also happens with MS, multiple sclerosis.

MOLLY WEBSTER: What does go away mean like, if I - we could talk specifically about MS or rheumatoid arthritis or both?

MELISSA WILSON: The inflammation that people have in rheumatoid arthritis around their joints, around their spine - it literally disappeared. For a subset of people, for a large subset of people, it's as if - it is the best possible treatment.

MOLLY WEBSTER: And rheumatoid arthritis - you know, for 75% of people, symptoms will go away. And in multiple sclerosis, it's like an 80% reduction in flare-ups.

LULU MILLER: Geez. I mean...

MOLLY WEBSTER: And not even just a reduction in the symptoms but in some cases, you actually get cognitive ability back.

LULU MILLER: No, no way.

MOLLY WEBSTER: It's huge. And so I had just, you know, these experts all telling me that, like, they have these anecdotal stories of women who just...

LULU MILLER: Yeah, yeah.

MOLLY WEBSTER: ...Want to be pregnant at the time because they get such relief in their symptoms or such a slowing of disease progression.

LULU MILLER: Yeah.

MOLLY WEBSTER: I mean, obviously, it is not a slam dunk for every individual or even every autoimmune disorder. Some of them actually get worse when you're pregnant, some say the same. Some we just have no data on and we don't know. But it does make you wonder.

MELISSA WILSON: The first OB-GYN that I met with...

MOLLY WEBSTER: You'll remember Melissa at the top of the episode told us that she's pregnant and that she recently developed Hashimoto's.

MELISSA WILSON: He said, oh, my colleague was just telling me about this paper they read about pregnancy and how it shaped the immune function. I was like, that's me (laughter).

MOLLY WEBSTER: And now that she sort of, like, stepped into her own research in this pretty novel way, she's actually quite curious to see if pregnancy alleviates her own autoimmune symptoms.

MELISSA WILSON: And so I'm actually going to be going, hopefully, to get testing in the next few months to see if the antibodies that my body is making to my thyroid have actually changed during the pregnancy.

MOLLY WEBSTER: OK. So there is one more part to her hypothesis, and it could offer an explanation for not only why females get autoimmune disorders more than males but why the incidence might be going up.

MELISSA WILSON: So for nearly all of human history, we didn't have contraception. And you could be pregnant for your entire reproductive career.

MOLLY WEBSTER: We now live in a world where, at least in Western or industrialized nations, people are getting pregnant way less. So we're not going through the cycle of having our immune system dragged down. So if it's on high all the time, maybe that in and of itself, the less pregnancies is actually contributing to why women today are getting autoimmune disorders more than in the past.

LULU MILLER: It's like, there's just more time that you're spent turbocharged.

MOLLY WEBSTER: There's more time spent at 10. And then your body is just like, I'm constantly at a 10.

LULU MILLER: Yeah.

MOLLY WEBSTER: Maybe I should go do something.

LULU MILLER: And so we think it's like, I've got nothing to do. Let me just start eating this body.

MELISSA WILSON: Wreaking havoc.

MOLLY WEBSTER: There's this weird thing where I'm like, oh, crap. I should get pregnant. Like - it's like - oh, and it's funny because one of my colleagues was like, you know, there's already so much societal pressure on women to, you know, follow to conform. And now, like, really, biology is telling us that 'cause we're not getting pregnant, you know, we're f***ing ourselves, essentially.

MELISSA WILSON: No, no, no.

MOLLY WEBSTER: Yeah.

MELISSA WILSON: No, keep going, though.

MOLLY WEBSTER: No but then the funny thing is then I think, like, the reverse of that is - like, you know, how many kids would be enough kids?

MELISSA WILSON: Yes.

MOLLY WEBSTER: You know?

MELISSA WILSON: We don't know, right? We don't know yet. We don't know if it - we don't know if it's more important that you start reproduction as soon as you're reproductively active or whether you maintain it over the whole course or is two enough, if you have one 10 years apart or - we have a zero idea.

MOLLY WEBSTER: So Melissa was basically like, OK, slow your roll. First off, there's so many things that can contribute to an autoimmune disorder. I don't think this is going to be your solution. Also, like, do you have one? Do you know you're going to get one? Like, we don't know...

LULU MILLER: Right, right, right.

MOLLY WEBSTER: ...Anything about them, really.

MELISSA WILSON: Science is not saying go get pregnant. It's not, a hundred percent not. What it's saying is that pregnancy may have shaped our immune systems. So let's figure out what components of our immune systems respond to the placenta, what components of our immune systems act independently of that. And then we can narrow in on the treatments.

MOLLY WEBSTER: Is anyone trying to study it?

MELISSA WILSON: Absolutely, yes.

MOLLY WEBSTER: OK.

RHONDA VOSKUHL: What is the factor?

MOLLY WEBSTER: Which brings us to...

RHONDA VOSKUHL: Hi, my name is Dr. Rhonda Voskuhl.

MELISSA WILSON: ...Our final scientist.

RHONDA VOSKUHL: I'm a professor of neurology at UCLA.

MOLLY WEBSTER: So Rhonda's out there in California working to understand what specifically, precisely is happening during pregnancy. And she's narrowing in on something that's being produced by the placenta at levels the body just hasn't seen before.

RHONDA VOSKUHL: Something happens during pregnancy whereby the fetal placental unit makes a kind of a novel estrogen. And this estrogen is called estriol.

MOLLY WEBSTER: And that is an estrogen called estriol.

RHONDA VOSKUHL: Now all of a sudden, you have this burst of a new estrogen, a different estrogen. And it's at a very high level.

MOLLY WEBSTER: And at the end of pregnancy, your body is flooded in estriol. And the baby's body is flooded in estriol. It's, like, a primary hormone that just skyrockets during the third trimester.

LULU MILLER: Wow.

RHONDA VOSKUHL: And then after delivery, it drops abruptly. Well, of course, it's made by the fetal placental unit.

MOLLY WEBSTER: Aka the placenta, who has been manning the estriol dials, has left the building. And I could probably tell you some boring things that wouldn't actually help you understand estriol more. It's just, like, a different-shaped molecule than other estrogens. It has particular functions for the fetus. It could be used in neural development. It's also used by the placenta to turn down the mom's immune system. And so she starts clinical trials. And she's been doing them since, like, 2007 and 2011. She takes nonpregnant women who have MS, and she gives them estriol.

RHONDA VOSKUHL: And we showed that it reduced these enhancing lesions by over 70%.

MOLLY WEBSTER: Symptoms go away. They see disease progression slow.

LULU MILLER: Whoa.

RHONDA VOSKUHL: The other thing that's pretty cool is as we were doing these trials in humans, there was an improvement in cognition. It is neuroprotective.

MOLLY WEBSTER: I basically was like, can I get some estriol, you know?

LULU MILLER: Yeah, I mean, well, I was Google - as you've been talking, I was like - are there estriol pills?

MOLLY WEBSTER: So it would be a pill, except it's not approved anywhere yet for MS. In Europe, I think some people might give it off-label because it's been approved for menopause.

LULU MILLER: Just for XX...

MOLLY WEBSTER: Just for...

LULU MILLER: OK.

MOLLY WEBSTER: Just for XX individuals or X-plus individuals.

LULU MILLER: And would this work? Could estriol work on a guy or an XY person?

MOLLY WEBSTER: That's an interesting question. I mean, theoretically, yes because it's a natural hormone. Rhonda says, like, you'd have to keep an eye out for different feminization things. Like, would it act on their breasts in a certain way. It works in XY mice.

LULU MILLER: Oh. So meaning, like, the XY mice given some estriol. And they...

MOLLY WEBSTER: Yeah, they...

LULU MILLER: Wow.

MOLLY WEBSTER: They saw a reduction in inflammation. Yeah, yeah, yeah. But they've not done any clinical trials on XY humans.

LULU MILLER: OK.

RHONDA VOSKUHL: There is a strong case to be made for estriol in MS women and probably rheumatoid arthritis. I think there's a case to be made in psoriasis. There's clearly a role for a pregnancy level of estrogen as a treatment for these autoimmune diseases in women who've already got the disease. I think there's clearly a role for further investigation into that.

LULU MILLER: And also, really quick, you said at the very beginning...

MOLLY WEBSTER: Yeah.

LULU MILLER: ...That, like, this is the work of provocative women. Why did you use the word provocative?

MOLLY WEBSTER: Because they're looking into stuff - like, when I talked a Montserrat, she said that, at the time, she was the only scientist in the world looking at X-inactivation in autoimmune disorder.

LULU MILLER: Really?

MOLLY WEBSTER: And do - that's stupid. That's like - that's insane to me. And Rhonda Voskuhl - like, she is - the studies that she's doing, like, nobody else was doing. And Melissa's pregnancy compensation hypothesis just came out two years ago. So I used the word provocative because they're asking questions and doing work that, like, nobody else is doing. And they're actually, like, upending science. Like, Montserrat's paper that showed that X-inactivation is not constant from time of embryo onwards is, like, upended.

LULU MILLER: Like, 17 textbooks had to be like, oh, we got to scratch out this dogma of how it works (laughter).

MOLLY WEBSTER: It's like the Earth is cracking, and they're the ones that caused the quake. Does that make sense? I don't know. I have no idea where this ends (laughter).

LULU MILLER: Yeah. But this - it sounds like what you found is, like, this very substantial start. It's - yeah.

MOLLY WEBSTER: That's the thing. That's - you know Rhonda's getting paper after paper after paper that says we're seeing estriol make a difference. And then we've got this X-inactivation stuff. Then we've got this pregnancy hypothesis. And it's like, it feels like we're at the - whether we like it or not, the very beginning of a story. So there really is no ending yet.

LULU MILLER: Hey, whatever happened to Melissa.

MOLLY WEBSTER: Oh, yeah. OK. So you know how she asked when the story was going to air?

(SOUNDBITE OF BABY LAUGHING)

MOLLY WEBSTER: That was two years ago.

Oh, hi, baby.

And when I jumped on the phone with her recently...

MELISSA WILSON: That's the 15-month-old, and the 3-month-old is sleeping.

MOLLY WEBSTER: ...I found out it has been quite the two years.

MELISSA WILSON: I have two pandemic babies. And one of them has gotten to be home with me 24/7 for his entire life (laughter).

MOLLY WEBSTER: Well, then I'll just say - OK. So maybe you can just tell me then about the pregnancy and what did end up happening 'cause I feel like that was, like, a cliffhanger...

(LAUGHTER)

MOLLY WEBSTER: ...In the interview, where for months, I was like, I wonder - I don't know what her symptoms are. And if she was having symptoms, like, I wonder if they went away.

MELISSA WILSON: So any symptoms that I would have acknowledged would have been tiredness, some hair loss and getting cold. But then when you're pregnant, your hair does wonky things and...

MOLLY WEBSTER: So her hair did get better when she was pregnant. Great. And she did feel less tired.

MELISSA WILSON: But...

MOLLY WEBSTER: But one thing did jump out at her. Before she was pregnant, as part of her disease, her thyroid was acting really wonky.

MELISSA WILSON: Occasionally, my thyroid antibodies, which is part of the way they diagnose it - they just spike up to, like, thousands of times larger than they should be. It's just like, they give you the test. And they say, like, oh, the range should be, you know, single digit to double digit. And when yours is in the thousands, you're like...

MOLLY WEBSTER: Wow. That's what it was, actually in the thousands.

MELISSA WILSON: Oh, yeah.

MOLLY WEBSTER: And then while she was pregnant...

MELISSA WILSON: My thyroid and my thyroid antibodies and everything was just normal.

MOLLY WEBSTER: ...Her numbers stopped spiking.

(SOUNDBITE OF BABY LAUGHING)

MELISSA WILSON: Yeah, yeah.

MOLLY WEBSTER: Did you - I remember you said to me - there are - I've talked to women who have been like, I just wish I could stay pregnant 'cause I feel so much better. That's not the reason for your back-to-back pregnancies. It wasn't like, I feel so much better. I'm going to stay pregnant.

MELISSA WILSON: (Laughter) No, no. It was that we wanted a second baby. And we're - and the universe saw fit that they should be so close together.

(SOUNDBITE OF BABY COOING)

MOLLY WEBSTER: Molly Webster. This episode was produced by Sindhu Gnanasambandan and Molly Webster.

LULU MILLER: And the Gonads theme song that you heard at the top of this episode was written, performed and produced by Majel Connery and Alex Overington.

MOLLY WEBSTER: Thanks for listening. Bye.

UNIDENTIFIED PERSON: RADIOLAB was created by Jad Abumrad and is edited by Soren Wheeler. Lulu Miller and Latif Nasser are our co-hosts. Suzie Lechtenberg is our executive producer. Dylan Keefe is our director of sound design. Our staff includes Simon Adler, Jeremy Bloom, Becca Bressler, Rachael Cusick, W. Harry Fortuna, David Gebel, Maria Paz Gutierrez, Sindhu Gnanasambandan, Matt Kielty, Annie McEwen, Alex Neason, Sarah Qari, Arianne Wack, Pat Walters and Molly Webster. With help from Shima Oliaee, Sarah Sandbach and Candice Wang. Our fact-checkers are Diane Kelly and Emily Krieger.

 

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