Marthe Gautier, 'Forgotten' Discoverer of Trisomy 21, Dies

Marthe Gautier, a French physician who was involved in the discovery of the extra chromosome that causes Down syndrome, died on Saturday, April 30. She was 96. This is an opportunity for us to look back and reflect on this discovery and the key role Gautier played in it. Like so many other women of her generation, she was a victim of what has come to be known as the Matilda Effect (see box).

Trisomy 21

Sixty-three years ago, the French Academy of Sciences received an article, "Human Chromosomes in Tissue Cultures" (1959), which reported the presence of an extra chromosome in patients with the syndrome that had been described by Langdon Down almost a century earlier. This was the first autosomal chromosome aberration recognized in the cells of humans; in 1960, it would be given the name "trisomy 21." History records the name Jérôme Lejeune, the first author listed on the article. The name of the woman researcher has, however, long since sunk into obscurity. Here's how that came to be.

A Year at Harvard

Born in 1925 to a long line of farmers in the Brie region of France, Marthe Gautier pursued her medical studies, intending to be a pediatrician. "In 1955, I defended my dissertation on pediatric cardiology. My advisor was Robert Debré," Gautier told the magazine La Recherche, which, the day after her death, republished the account she gave them in 2009 about the circumstances surrounding the discovery. Debré was the father of French pediatrics and, at the time, the leading practitioner in the field. Gautier — one of only two women among the 80 residents at Paris Hospitals — was doing brilliantly in her role when Debré nominated her for a scholarship to spend a year at Harvard University.

While she was continuing her studies there, she learned that her contract required her to, as she put it, "work part-time as a technician in a cell culture laboratory in order to obtain, from aortic fragments, in vitro cultures of fibroblasts, poorly differentiated cells." This was an opportunity for the student to acquire expertise in a new area.

When she returned to France, she took a job at Trousseau Hospital as the chief clinical resident in the pediatric cardiology department, which was headed by Raymond Turpin. Turpin was studying multiple malformation syndromes. The most common was what at the time was called "mongolism" — now known as Down syndrome — a disorder characterized by intellectual disability and morphologic anomalies. He put Gautier in charge of developing cell cultures. She took all she had learned during her time in the United States and put it to good use, setting about to count chromosomes. This was not an easy thing to do because, in the 1950s, "we were at year zero in France when it came to cell cultures." Gautier chose to "work on fibroblasts derived from connective tissue, because it's easy to obtain under local anesthesia." She developed her own experimental protocol and fully invested herself in it — sometimes quite literally by using her own serum, and even her own money to purchase lab equipment.

When at last she succeeded in cultivating connective tissue, she adapted a recent technique that allowed inducing "hypotonic shock." She would dry the slide after fixation to sufficiently disperse the chromosomes of dividing cells, thus making it easier to count them. But she added her own special touch: "The dye that I used was my own recipe," she pointed out when recalling her discovery. Then she saw what the process had revealed: the cells of normal children had 46 chromosomes, but the cells of those with mongolism had 47.

Second Place

However, Gautier wasn't able to identify this extra chromosome with her old, low-resolution microscope. That's when Jérôme Lejeune, a researcher at the French National Center for Scientific Research (CNRS) and one of Turpin's students, offered to have her slides photographed at a lab that had better equipment. Gautier agreed and gave them to him. This was in May 1958. The young woman expected an article to be written, but nothing happened. "I didn't see the photos: they were, they told me, with the boss, who was not communicative," Gautier wrote many years later. "I had a strange feeling, an unsettling feeling, that in the end, this situation was going to leave me embarrassed." About 3 months later, Lejeune attended a genetics seminar in Montreal where he spoke about the "French discovery," photos in hand.

The cherry on top? When the article first appeared in January 1959 in Proceedings of the French Academy of Sciences, not only had Marthe Gautier not been informed about it, but her first name appeared as "Marie" and her last name as "Gauthier." And that name was listed second, after Jérôme Lejeune — which, she pointed out, was "contrary to the usual practice, where the first name is that of the researcher who designed and carried out the experiments."

Since then, this discovery has been associated with Lejeune, who promoted it by presenting himself on the international science scene as the "discoverer" of the first human chromosome abnormality — which, in 1960, the Denver Conference named trisomy 21. Lejeune would devote the rest of his career to studying this genetic disorder, the topic of his dissertation in 1961. That same year, he would be awarded the CNRS Silver Medal and, together with Turpin, the Prix Jean Toy. In 1962, Lejeune would discover trisomy 16. In 1964, he would become a professor of genetics. And in 1969, he would receive the William Allan Award, one of the most prestigious in the field of genetics.

Gautier left that field behind, devoting the rest of her career to pediatric cardiology. "As for me, I felt a moral obligation, and following my deeply held beliefs, I left that path to return to the one that would guide me to focus on treating children with heart disease — an area in which, prior to that adventure, I had been deeply involved." And with this, she plainly and simply brought her story to a close.

But even though Gautier didn't clamor for acknowledgment for having gotten the ball rolling on the discovery of the extra chromosome, her name wasn't completely erased from history.

Inserm Recognizes Gautier

The controversy started with the story published by La Recherche, excerpts of which can be found in the magazine's article on Gautier's death. This was in 2009 — 50 years after the fact. Fast forward to January 2014. As France Culture described it: "Marthe Gautier was about to receive the French Society of Human Genetics Grand Prix at a conference in Bordeaux when bailiffs showed up, court order in hand, to ensure, on behalf of the Jérôme Lejeune Foundation, that her remarks would not damage the late doctor's reputation. The organizers cancelled her event and, during a private ceremony at her hotel, gave the then 88-year-old her medal."

But it took the intervention of the French National Institute of Health and Medical Research (Inserm) to confirm the decisive role that Gautier had played in the discovery. Its Ethics Committee was asked to look into the matter by a group of biologists who were outraged by the tactics employed by the Jérôme Lejeune Foundation — also known for its arguments against abortion. In an opinion published in September 2014, the Ethics Committee unambiguously took Gautier's side, setting down for all to see that, "given the context at the time of the extra chromosome's discovery, Jérôme Lejeune's participation in it is unlikely to have been preponderant, except in his not giving credit to the training of people (ie, Marthe Gautier) that led to their acquiring expertise (ie, in cell culture), a fortiori when associated with a period of time spent outside of France (ie, in the USA)." There is no doubt that Jérôme Lejeune promoted the discovery, but, as the Ethics Committee wrote, "that is different from making the discovery." And indeed, "the technical approach is a condition necessary to the discovery" — and that's where Marthe Gautier played the "key role."

To drive their point home, the Ethics Committee stated the following: "Given that the discovery of Trisomy 21 could not have been made without the indispensable contributions of Raymond Turpin and Marthe Gautier, it is regrettable that their names have not been routinely associated with this discovery, both in the press and in the awarding of various honors."

This article was translated from the Medscape French edition.

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Cite this: Stéphanie Lavaud. Marthe Gautier, 'Forgotten' Discoverer of Trisomy 21, Dies - Medscape - May 18, 2022.