February 5, 202516 min readWho Discovered the Cause of Down Syndrome?It took more than 50 years for Marthe Gautier to set the record straight about her discovery of the genetic cause of Down syndrome Selina PavelIn the mid-1950s Marthe Gautier, a young French doctor and cytogenetics researcher, led a cutting-edge experiment to investigate the cause of Down syndrome. She painstakingly cultured cells in a ramshackle lab until one day she discovered an extra chromosome in the cells of people with Down syndrome. This proved beyond a doubt that Down syndrome is genetic.In this first episode of our two-part series about Gautier, who passed away in 2022, she sees her discovery appropriated by a male colleague as he rushes to publish her findings. Jrme Lejeune is listed as the lead author of the study about the discovery even though Gautier did the work. Her name is listed second on this groundbreaking paper, published in 1959. And to add insult to injury, it is misspelled. It will take decades for Gautier to speak out.LISTEN TO THE PODCASTOn supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.TRANSCRIPTTatiana Giraud: So that's me, uh, playing the flute with Marthe, uh, and with, uh, the piano and my sisters.Lorena Galliot: This is Tatiana Giraud. She's a research director in evolutionary biology. We're sitting in her office at a botanical campus about 45 minutes outside of Paris.My colleague, Sophie, and I came here to discuss Dr. Marthe Gautier, a French doctor who also happens to be Tatiana's great-aunt. That's for her painting. 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 Tiana and her siblings gifts from her travels.Right now, we're huddled around Tatiana's laptop, looking at old family photos.Tatiana Giraud: Yeah, so, um, it's Marthe in her flat in Paris when she was 80.Lorena Galliot: In this photo that Tatiana is 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.Tatiana Giraud: Oh yeah, she had a lot of papers everywhere in her flat.Lorena Galliot: So far it's been all smiles as we look through these old photos, but then Tatiana's tone changes...Tatiana Giraud: and actually, so she has a perruque, a wig.Lorena Galliot: A wig?Tatiana Giraud: Uh, because actually, because of this story, uh, with Jrme 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.Lorena Galliot: Wow.Tatiana Giraud: At that time, uh, really because of that.Lorena Galliot: 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 Gautier herself would finally blow the whistle on.Marthe Gautier (in French with voice-over): I was very sad and very upset when I saw the order of the names. Lejeune, Gautier, Turpin. To me, it was an insult.Lorena Galliot: 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 our 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 and 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.Tatiana Giraud: Actually, so her father, uh, sold, uh, like a cow, um, how do you say that? Un troupeau de vache.Lorena Galliot: Uh, a cow. Oh, wow. Yeah, yeah.Tatiana Giraud: A whole uh.Lorena Galliot: Like a herd of cows.Tatiana Giraud: Yeah. Exactly, to buy her a flat in Paris.Lorena Galliot: 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.Tatiana Giraud: She had to be twice as good. So maybe that was kind of a burden and, um, forced her to be, uh, more independent and more successful.Lorena Galliot: 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 Pariss 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.David Wright: In the post-war period, the infrastructure in France and Europe, et cetera, have been devastated by the war. The funding was thread bear.Lorena Galliot: 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.David Wright: The U.S. was just overflowing with money and resources and, you know, Gautier 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, this old traditional 19th-century French hierarchical approach. And soLorena Galliot: So when Marthe has 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, MartheDavid Wright: She got a part-time job there and learned, really, state-of-the-art cell culture treatment and staining and photography.Lorena Galliot: 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.Anita Bhattacharyya: 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.Lorena Galliot: That's Anita Bhattacharyya. She runs a lab at the University of Wisconsin, Madison, where cell culture is used to study the brain of people with Down syndrome.Anita Bhattacharyya: So, it's a way to look into tissue in a way you can't otherwise, and see the behavior of the individual cells.Lorena Galliot: Cell culture as 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.Anita Bhattacharyya: 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.Lorena Galliot: 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 Hpital 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.David Wright: 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.Lorena Galliot: 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 Jrme 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.David Wright: He had done a lot of work on fingerprint, uh, analysis and, uh, single palmar crease in Down syndrome individuals. And so, this was sort of leading him in a certain way, research-wise, it didn't necessarily bear that much fruit.Lorena Galliot: But in the mid-1950s, when Marthe Gautier 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.[mid-roll]Lorena Galliot: We're back with the story of Marthe Gautier. 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.Anita Bhattacharyya: Cytogenetics is really being able to look into a cell and see the chromosomes within the cell.Lorena Galliot: That's Anita Bhattacharyya again.Anita Bhattacharyya: And so that was just emerging at the time of Dr. Gautier'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 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.Lorena Galliot: 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 microscopeDavid Wright: It's sort of like looking at pieces of spaghetti through the bottom of a Coke bottle.Lorena Galliot: 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.David Wright: It wasn't until actually 1956 that there is definitive scientific evidence that says, okay, you know, we, we, we know now there's, there's 46, it's not 48, it's not 47, it doesn't differ between, you know, it's, it's supposed to be, as it were, 46.Lorena Galliot: So to summarize, just as Marthe Gautier 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 Turpin, Marthes 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.Lorena Galliot: 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.Marthe Gautier (in French with voiceover):If you give me a lab, a room, I will be able to culture cells. I know how to do it.Lorena Galliot: That's Marthe Gautier 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.Marthe Gautier (in French with voiceover):He gave me this sort of sideways look as if he was thinking, is this young lady making up tales?Lorena Galliot: This is David Wright again.David Wright: Gautier sort of said, well, actually, I was doing this for the entire year in Boston. So he sort of sets her up with this ramshackle lab.Lorena Galliot: 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.Tatiana Giraud: Because after the war, there was really no resources, so she had to make a loan on herself, uh, to borrow money. And, uh, so she paid herself for the material and everything. Like, um, 100,000 francs at the time.Lorena Galliot: Not only does Marthe need to take out a loan of about 2,600 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.Marthe Gautier (French with English voiceover):The poor resident was woken up by a rooster crowing loudly every morning, so that's what went down in hospital history.Lorena Galliot: 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.Marthe Gautier (in French with voiceover):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.Lorena Galliot: 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 onenearly two years latershe repeats the experiment.Marthe Gautier (in French with voice over): And that's when I saw there were 47 chromosomes.David Wright: Even using the bad, bad microscopes that she had, she could see that they had 47 rather than 46 chromosomes.Lorena Galliot: It's a startling discovery. A big discovery. And in order to tell the world, Marthe needs proof. She needs photographs.And her lab doesn't have the equipment to do this. But Marthe's in luck. Jrme Lejeune, the young researcher who'd been working closely with Turpin when Marthe arrived at the lab, offers to help.David Wright: He's a young, in effect what we would call in North America, a fellow. He's in the hospital before Gautier comes back from Boston. So you could argue that he's, he's a little bit more senior, not a lot. But he's been there a couple more years. So on the, on the very important hierarchy of that team, he's maybe one rung, as it were, above, uh, Gautier, uh, in terms of authority in the hospital.Clara Gaymard: My father started in 52, at the pediatric department of the professor, Raymond Turpin.Lorena Galliot: That's Clara Gaymard. She's Jrme Lejeune's daughter.Clara Gaymard: And he decided in the very beginning to, uh, 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.Lorena Galliot: She published a biography of her father based on his memoir.She explains that before Marthe joined Turpin's lab in 1956, Jrme Lejeune had already been trying to figure out the origin of Down syndrome for several years.Clara Gaymard: My father was obsessed by that. He wanted to discover why they were sick, to be able to find a way to cure them.Lorena Galliot: So until then, Jrme'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.Clara Gaymard: He worked very closely with Marthe Gautier on this technique. Really, uh, Jrme Lejeune has the best relationship with Marthe Gautier.Lorena Galliot: There is some evidence to support Clara's statement. Letters that Marthe and Jrme 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.Jrme Lejeune was her boss's protg. 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 Jrme offers to take the slides to a lab he has access to to get them photographed, Marthe trusts him. She gives him her slides. And then she waits. And she waits. And nothing.David Wright: I think the important thing about the story from Gautier'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, what are the photographs? He said, well, I gave them to Turpin.Lorena Galliot: But Jrme 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.David Wright: And it's not clear whether Turpin would have been very happy if he'd known that, that basically, Lejeune was blabbing about this potentially, you know, international scientific discovery in public.Lorena Galliot: And then, in early 1959, Marthe gets a call. It's Jrme Lejeune. He reads a short paper to her over the phone. It's a paper about her slides. Her research. Jrme 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, Jrme 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 Jrme 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.David Wright: 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.Lorena Galliot: 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, aka trisomy 21. Anyway, the paper is rushed out. It's called Human Chromosomes in Tissue Culture.Jrme Lejeune is the first author, Raymond Turpin is the third and senior author, and sandwiched between the two of them is Marthe Gautier. 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.Lorena Galliot: Tatiana Giraud again.Tatiana Giraud: 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.Lorena Galliot: But it was too late. The paper had come out and the discovery had slipped through Marthe Gautier's hands.Next week on Lost Women of Science:Tatiana Giraud: But Jrme Lejeune not only took the discovery, but also really used it to launch his career.David Wright: Gautier 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 Galliot. Hansdale Hsu was our sound engineer. Lexi Atiya was our fact-checker. Our thanks go to co-executive producers Amy Scharf and Katie Hafner, senior managing editor Deborah Unger, and program manager Eowyn Burtner. Thanks also to Jeff DelViscio at our publishing partner, Scientific American.Audio of Marthe Gautiers interviews is from INA, the French Audiovisual Institute. And from Wax Science, a non-profit promoting women in science. We're grateful to Hlne Chambefort and the archivists at INSERM, the Jrme Lejeune Foundation, as well as to Laurent Apfel and Cline Curiol 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 lost women of science.org. And don't forget to click on that omnipresent, donate button.Follow us on Facebook and Instagram at @LostWomenSci. That's at Lost Women of Sci. Thank you so much for listening. I'm Lorena Galliot. See you next week.Senior Producer and HostLorena GalliotSenior Producer and Sound DesignerSophie McNultyGuestsTatiana GiraudTatiana Giraud is Marthe Gautiers grand-niece. She leads the National Center for Scientific Research (CNRS) Evolutionary Genetics and Ecology team, University of Paris-Saclay.David WrightDavid Wright is Professor and Canada Research Chair in History and Classical Studies at McGill University.Anita BhattacharyyaAnita Bhattacharyya is Associate Professor of Cell and Regenerative Biology at the Waisman Center, University of Wisconsin-Madison.Clara Lejeune GaymardClara Lejeune Gaymard is the daughter of Jrme Lejeune. She is co-founder of the innovation investment group RAISE, as well as the author of Life Is a Blessing: A Biography of Jrme LejeuneGeneticist, Doctor, Father, first published in French in 1997.Further ReadingRandy Engel Interview with Dr. Marthe Gautier, Discoverer of Trisomy 21, by Randy Engel, in RenewAmerica. Published online March 26, 2013Downs Syndrome: The History of a Disability, by David Wright. Oxford University Press, 2011