Who Discovered the Cause of Down Syndrome? Episode One
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She's a research director in evolutionary biology.

We're sitting in her office at a botanical campus about 45 minutes outside of Paris. I also love all the plants in your office as well. My colleague Sophie and I came here to discuss Dr. Marthe Gauthier, a French doctor who also happens to be Tatiana's great-aunt. Tatiana's own grandmother died before she was born. So Marthe stepped in. She hosted Christmas.

She came to visit for birthdays and other holidays, and she bought Tatiana and her siblings gifts from her travels. Right now, we're huddled around Tatiana's laptop, looking at old family photos. In this photo Tatiana's showing us, Marthe looks straight at the camera with a piercing expression.

She's wearing a yellow polo shirt, a black cardigan, and she's holding a magnifying glass that she used to help her read. She's sitting at her dining table in this massive room with ornate wall moldings and bookshelves, and spilling out from the bookshelves and completely submerging the table are papers. Oh yeah, she had a lot of papers everywhere in her flat. So far it's been all smiles as we look through these old photos, but then Tatiana's tone changes.

And actually, so she has a perruque. A wig. A wig, because actually, because of this story with Jérôme Lejeune and the 2014 story, that really upset her. She had forgotten about all this and it came back quite violently. And she lost her hair at that time, really because of that. Wow, wow.

This story that culminates in an incident in 2014 that led an 88-year-old scientist to lose all of her hair. This story is the heart of today's show. It's a story that says a lot about how women scientists were treated in a country like France in the 1950s. Treatment that, decades later, Marthe Gauthier herself would finally blow the whistle on.

I was very sad and very upset when I saw the order of the names. Lejeune, Gautier, Turpin. To me, it was an insult. I'm Lorena Galliott, and this is Lost Woman of Science, where we tell the stories of groundbreaking women who never got the recognition they deserved until now.

This is a story of a woman who played a key role in a discovery that advanced her understanding of Down syndrome and many other genetic diseases. But for 50 years, the face of that discovery was someone else, and Marthe was all but forgotten. Today's episode, Who Discovered the Cause of Down Syndrome? This is part one. Before we get to that incident in 2014, when Marthe lost all her hair in distress...

Let's go back to the beginning. Marthe was born in September 1925 on a farm in Montigny, about 60 miles east of Paris. She was the fifth of seven children. Marthe didn't come from a family of scientists. Her parents were farmers. There was no master plan that she'd one day take up a white coat. But her mother was ahead of her time.

She encouraged her daughters to pursue higher education, even if their family wasn't part of the Parisian elite who traditionally attended the country's top schools. And Marthe was smart and hardworking. So she followed in her older sister's footsteps and moved to Paris to study medicine. Actually, so her father sold like a cow, a cow's

How do you say that? Un troupeau de vaches. Oh, wow. Yeah, yeah. Like a herd of cows. Yeah, exactly, to buy her a flat in Paris. So Marthe moves to Paris in 1942, in the middle of the Second World War. Then in 1944, there's a big battle in the city between German and Allied troops, and tragically, Marthe's sister is killed. Later on...

Marthe would write that after her sister died, she had to be both her sister and herself. She had to be twice as good, so maybe that was kind of a burden and forced her to be more independent and more successful. And Marthe was very successful. She was a brilliant student. In 1952, she's one of just two women out of 80 students from all of France to pass the residency entry exam for Paris' top hospitals.

She trains in pediatric cardiology. In 1955, she completes her dissertation on rheumatic fever in infants. But this is the post-war period in France. In the post-war period, the infrastructure in France, in Europe, etc., had been devastated by the war. The funding was threadbare. That's David Wright. He's a professor of the history of medicine at McGill University in Montreal. He wrote a book that's key for this story.

It's called Downs, The History of a Disability. He explains that not only were resources in France extremely limited at the time, but also French medical systems were very rigid and very hierarchical.

The U.S. was just overflowing with money and resources and, you know, Gauthier and others would go to the U.S. and go, oh my God, it's just like the incredible, the facilities are fantastic. People are collaborative rather than the so traditional 19th century French hierarchical approach. And so when Muth is offered a fellowship to study pediatric cardiology in the United States at Harvard Medical School, she jumps at the chance. In September of 1955,

Marthe boards a steamship with two other fellows from France, both men, to make the five-day trip across the Atlantic to Boston. At Harvard, Marthe studies pediatric cardiology and rheumatic fever. And she also works as an assistant at a lab. And by a twist of fate, one that turns out to be very important, someone at the lab goes on maternity leave.

So, Marthe... She got a part-time job there and learned, really, state-of-the-art cell culture treatment and staining and photography. Let's take a step back for a moment. We're going to explain exactly what cell culture is, because this detail is actually an important one for this story. So, cell culturing is the ability to take a piece of tissue, let's say, from a plant or an animal or a person, and put that

tissue in a culture dish with media and allow the cells in that tissue to survive, first of all, but also to show some of their behavior. That's Anita Bhattacharya. She runs a lab at the University of Wisconsin-Madison where cell culture is used to study the brain of people with Down syndrome.

So it's a way to look into tissue in a way you can't otherwise and see the behavior of the individual cells. Cell culture is a basic technique emerged in the late 1800s. But now, in the 1950s, it's starting to be used for something new, looking at genetic material.

These new techniques were being developed mostly in the U.S. and Sweden, very little in post-war France. It actually still is kind of specialized. It was very hands-on. It wasn't take your cell, put it in a machine, it comes out, it looks the way you want it to. It was a lot of finesse, I would say, and tedium to get things the way you want them, get the preparation right.

I have to say, I've only done it once. I thought it was really hard. And now Marthe, while she's in Boston, has just been specially trained in this highly technical skill, something that's still quite new. She happens to be at the right place at the right time. After her year in Boston, Marthe returns to France. But there, the position she was hoping to get in pediatric cardiology, her specialty, doesn't work out.

So she takes a job in a different department, with a doctor named Raymond Turpin. Raymond Turpin was a senior professor at the time. He headed the pediatrics department at the Hôpital Trousseau. It's a hospital in the southeast of Paris. He ran it in that very rigid, very hierarchical way that historian David Wright described earlier in the episode.

You actually see these photographs of Turpin and his team, and there's like 25 of them or so, and they're dressed differently depending upon their seniority, etc. And unsurprisingly, the overwhelming majority of them are men. Turpin has always been interested in what's now known as Down syndrome. And at this time, he's working with a young doctor on his team called Jérôme Lejeune. They're analyzing the physical characteristics in the palms and the fingers of people with Down syndrome.

In particular, single palmar crease, a trait often found in people with Down syndrome where the person has one crease on their palm instead of two or three. He had done a lot of work on fingerprint analysis and single palmar crease in Down syndrome individuals. And so this is sort of leading him in a certain way. Research wise, it didn't necessarily bear that much fruit.

But in the mid-1950s, when Marthe Gauthier joins the team, an entire new field is emerging that completely changes the focus of their research. And again, Marthe happens to be at the right place at the right time. What was this brand new field? And what did Marthe bring to the table? Find out after the break.

Marguerite Hilferding basically created the field of psychoanalysis that Freud and Jung credited in their papers, yet no one's heard of her. Dr. Charlotte Friend discovered the Friend's leukemia virus, proving that viruses could be the cause of some types of cancers. Yvette Cochois discovered the element astatine and should have won the Nobel Prize for that.

Is there a lost woman of science you think we should know about? You can tell us at our website, lostwomenofscience.org, and click on Contact, where you'll find our tip line. That's lostwomenofscience.org, because it takes a village to tell the stories of forgotten women in science. We're back with the story of Marthe Gauthier. So what's the thing with this new field of research that's exploding just as Marthe was coming home from Boston?

Well, for one, it's called cytogenetics. Cytogenetics is really being able to look into a cell and see the chromosomes within the cell. That's Anita Bhattacharya again. And so that was just emerging at the time of Dr. Gauthier's work, where people were just starting to be able to take cells and look at the chromosomes. So it's a combination of good genes

cell culture, but also knowing how to treat the cells in a way that you could make the chromosomes act like they might act in a tissue. So chromosomes, as you might remember from high school biology, are the structures in our cells that carry our genetic material, our DNA. Two points to highlight. One, cytogenetics, the study of chromosomes, was very new.

And two, cell culture was the backbone of this research field. Without proper cell culture, chromosomes in cells are almost impossible to see. When you look through a microscope... It's sort of like looking at pieces of spaghetti through the bottom of a Coke bottle.

Historian David Wright explains that for the first half of the 20th century, no one knew exactly how many chromosomes were present in a human cell. It wasn't until actually 1956 that there is definitive scientific evidence that says, OK, you know, we know now there's 46. It's not 48. It's not 47. It doesn't differ between, you know, it's supposed to be, as it were, 46.

So, to summarize, just as Marthe Gouthier returns to France, it becomes clear that under normal circumstances, humans always have 46 chromosomes, which come in 23 pairs. This sets off a scientific race to find out what happens to chromosomes in situations that are not normal. Finding abnormalities in chromosome counts would allow researchers to determine, once and for all,

if a certain condition was genetically linked. One of the researchers to enter this race is Raymond Durbin, Marthe's new boss. He suspects, and he's not the only one, that Down syndrome is genetic. People with Down syndrome share similar characteristics, and consistent and striking shared characteristics can often denote a genetic cause.

So in 1956, Turpin wants to apply this new understanding of human chromosomes to analyze the cells of people with Down syndrome. There's only one problem: almost no one in France at the time knows how to culture cells to study chromosomes. Certainly no one on Turpin's team. Or so he thinks.

If you give me a lab, a room, I will be able to cut herself. I know how to do it. That's Marthe Gauthier herself. It's an interview she gave French television in 2018, when she was 92. She's recalling this 1956 staff meeting of Turpin's team.

And according to her, she volunteered to lead an experiment aiming to identify the chromosomal cell count of people with Down syndrome. As she remembers it, Turpin was surprised to hear what this new young woman on his team claimed to be able to do. He gave me this sort of sideways look as if he was thinking, is this young lady making up tales? This is David Wright again. Gautier said, well, actually, I was doing this for the entire year in Boston.

So he sort of sets her up with this ramshackle lab. Ramshackle is a good way to describe it. Turpin provided Marthe with a room, a centrifuge, and a microscope, but not much else. Here's Marthe's great-niece, Tatiana Giraud, again.

Because after the war, there were really no resources. So she had to make a loan on herself to borrow money. And so she paid herself for the material and everything, like 100,000 francs at the time. Not only does Marc need to take out a loan of about 2600 US dollars in today's money, she also has to get creative with other things.

For example, she draws her own blood for the human serum and she brings a rooster down from her family farm to gather its plasma. She even asks one of the nurses who lives on the hospital grounds if she can keep the rooster in her yard. The poor resident on call was woken up by a rooster crowing loudly every morning, so that's what went down in hospital history.

The trickiest part is actually getting the right kind of human tissue for this sort of analysis. But Marthe eventually, luckily, got eye tissue samples from deceased hospital patients. Once she has these, she gets to work. She carefully cultures cells from patients without Down syndrome

to compare against samples of patients with Down syndrome. I prepared the same cell cultures for four months, and I always counted 46 chromosomes in the cells. After these four months, I said to myself, let's do it. By which she means she was ready to try it on tissue samples from people with Down syndrome. But those samples are even harder to come by.

So when she finally obtains one, nearly two years later, she repeats the experiment. And that's when I saw there were 47 chromosomes. Even using the bad microscopes that she had, she could see that they had 47 rather than 46 chromosomes. It's a startling discovery. A big discovery. And in order to tell the world, Marc needs proof.

She needs photographs, and her lab doesn't have the equipment to do this. But Marthe is in luck. Jérôme Lejeune, the young researcher who'd been working closely with Durbin when Marthe arrived at the lab, offers to help.

He's a young, effective, what we will call in North America, fellow. He's in the hospital before Gaultier comes back from Boston. So you could argue that he's a little bit more senior. Not a lot, but he's been there a couple more years. So on the very important hierarchy of that team, he's maybe one rung, as it were, above Gaultier in terms of authority in the hospital.

My father started in 1952 at the pediatric department of the professor Raymond Turpin. That's Clara Guémard. She's Jérôme Lejeune's daughter. And he decided in the very beginning to try to understand why, what you call in English Down syndrome, why they were like that. And it was very original at this time to think about a chromosomal origin. She published a biography of her father based on his memoir.

She explains that before Marthe joined Turpin's lab in 1956, Jérôme Lejeune had already been trying to figure out the origin of Down syndrome for several years. My father was obsessed by that. He wanted to discover why they were sick to be able to find a way to cure them. So until then, Jérôme's research had focused on the fingerprints of babies born with Down syndrome. In fact, he published a few papers on this.

And then, the discovery of the 46 chromosomes came along and opened these new avenues of research. According to Clara, her father immediately saw the potential of this new avenue, and he worked closely with Marthe on her experiment. He worked very closely with Margautier on this technique. Really, Jérôme Lejeune has the best relationship with Margautier. There is some evidence to support Clara's statement.

Letters that Marthe and Jérôme Lejeune exchanged at the time show that they addressed each other in a friendly and collegial way. But of course it's impossible to know what Marthe truly felt inside. Jérôme Lejeune was her boss's protégé. She was an outsider. He was educated in Paris, at a well-known Catholic private school. She was a farmer's daughter from the provinces. She may have felt that she had to remain in his good graces. Or maybe their working relationship had been perfectly pleasant.

Until this point. In any case, when Jerome offers to take the slides to a lab he has access to to get them photographed, Mark trusts him. She gives him her slides. And then she waits. And she waits. And nothing.

I think the important thing about the story from Gauthier's standpoint is that Lejeune never showed her the photographs. So she saw them through the microscope, right? So she knew what she had. But then he took the photographs. She said, where are the photographs? He said, well, I gave them to Turpin. But Jérôme Lejeune didn't just hand over the photographs to Turpin. In fact, he took them with him to the International Congress of Genetics in Montreal in 1958. And although he didn't formally present them, he began showing them to people.

He even gave an impromptu seminar at McGill University presenting the findings. And it's not clear whether Turpin would have been very happy if he'd known that basically Lejeune was blabbing about this potentially, you know, international scientific discovery in public. And then in early 1959, Marc gets a call. It's Jérôme Lejeune. He reads a short paper to her over the phone. It's a paper about her slides, her research.

Jérôme asks Marthe if she has any corrections. The paper is coming out next week. Marthe is startled. Until then, she hadn't even known a paper was in the works. It was only later that Marthe actually learned what happened. This is what went down. First, Jérôme showed the slides to Turpin. Turpin was skeptical. He wanted to see more proof. But then, they learned that a Scottish team had conducted a very similar experiment and they were very close to publishing.

So Jérôme Lejeune and Turpin rushed to get theirs out first. They published the findings in a weekly roundup of presentations at the French Academy of Science. This is a kind of weekly scientific news bulletin, basically that meant that research could be highlighted without going through the standard peer-reviewed journal route, which can take months.

That was a sort of mad rush in early 59 to get the article out so they could be the first to actually claim that they had discovered a non-sex-specific trisomy. So real quick, the term trisomy, or trisomy as it's pronounced in the United States, means having three copies of a chromosome instead of two. And it would, in the not-too-distant future, be associated with Down syndrome, a.k.a. trisomy 21.

Anyway, the paper is rushed out. It's called Human Chromosomes in Tissue Culture. Jérôme Lejeune is the first author. Raymond Turpin is the third and senior author. And sandwiched between the two of them is Marthe Gauthier. But her name is misspelled. She's listed as Marie, not Marthe, and Gauthier with an H. Which for me is like the smoking gun in this entire story.

Tatiana Giraud again. I don't see how he can claim anything because she did all the work about the cell culture, so he only took the picture. But it was too late. The paper had come out and the discovery had slipped through Marthe Gauthier's hands. Next week on Lost Women of Science. But Jérôme Le Hyen not only took the discovery, but also really used it to launch his career.

Gauthier would come out and say, hey, let's wait a second here, right? He was not the saint that some people are painting him out to be. This has been Lost Women of Science. This episode was produced by Sophie McNulty and me, Lorena Galliott. Hans Del Schee was our sound engineer. Legzia Tia was our fact checker. Our thanks go to co-executive producers Amy Scharf and Katie Hafner.

Senior Managing Editor, Deborah Unger, and Program Manager, Ewan Bertner. Thanks also to Jeff DelVicio at our publishing partner, Scientific American. Audio of Marc Gautier's interviews is from INA, the French Audiovisual Institute, and from Boix Science, a non-profit promoting women in science.

We're grateful to Hélène Chamfort and the archivist at INSERM, the Jérôme Lejeune Foundation, as well as to Laurent Affel and Céline Curiolle for their help with this episode. Thank you also to Selina Pavel, who created the art. Lost Women of Science is funded in part by the Alfred P. Sloan Foundation and the Anne Wojcicki Foundation. This podcast is distributed by PRX.

You can learn more about our initiative at lostwomenofscience.org. And don't forget to click on that omnipresent donate button. Follow us on Facebook and Instagram at at Lost Women of Sci. That's at Lost Women of S-C-I. Thank you so much for listening. I'm Lorena Galliott. See you next week. Hi, I'm Katie Hafner, co-executive producer of Lost Women of Science. We need your help.

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