Marthe Gautier, “forgotten” from the discovery of trisomy 21, died

Marthe Gautier, a French doctor involved in the discovery of the extra chromosome that causes Down syndrome, passed away on Saturday, April 30. She was 96 years old. This is an opportunity for us to come back to this discovery and the key role that Gautier played in it. Like so many other women of her generation, she was the victim of what has been called the Mathilde 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 described by Langdon Down almost a century earlier. . This was the first autosomal chromosomal aberration recognized in human cells; in 1960, it was given the name “trisomy 21“. History records the name of Jérôme Lejeune, the first author cited on the article. The name of the researcher, however, has long since fallen into oblivion. Here’s how it happened.

The Matilda effect

Many women go unrecognized for the often central role they played in scientific discoveries – and that’s when they aren’t simply erased from the annals of science or outright excluded from the awarding of prizes, even the most prestigious. There’s Jocelyn Bell Burnell, the British astronomer who discovered pulsars. There is Rosalind Franklin, who pioneered the field of molecular biology with her discovery of the double helix structure of DNA – a discovery which has been attributed to three men, James Watson, Francis Crick and Maurice Wilkins, who later received a Nobel Prize. . In the 1990s, science historian Margaret Rossiter coined the term “Mathilde Effect”, describing it as the phenomenon in which female scientists are “ignored, discredited or otherwise overlooked”. At best, they receive due recognition for their discoveries, and even then, only many years after the fact.

A year at Harvard

Born in 1925 from a long line of farmers in the Brie region of France, Marthe Gautier continued her medical studies, aiming for pediatrics. “In 1955, I defended my thesis on pediatric cardiology. My supervisor was Robert Debré,” Gautier told the magazine. The researchwho, the day after his death, republished the Account she gave them in 2009 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 of Hôpitaux de Paris – was doing brilliantly in her role when Debré nominated her for a scholarship to spend a year at Harvard University.

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

Back in France, she took a job at the Trousseau Hospital as head of the internal clinic of the pediatric cardiology department directed by Raymond Turpin. Turpin studied multiple malformation syndromes. The most common was what was then called “mongolism” – now known as Down syndrome – a disorder characterized by intellectual disability and morphological abnormalities. He instructs Gautier to develop cell cultures. She took everything she had learned during her time in the United States and put it to use, starting to count chromosomes. It was not easy because, in the 1950s, “we were at year zero in France as far as cell cultures are concerned”. Gautier chose to “work on fibroblasts from connective tissue, because it is easy to obtain under local anesthesia.” She developed her own experimental protocol and was fully invested in it – sometimes literally using her own serum, and even her own money to buy lab equipment.

When she finally succeeded in cultivating connective tissue, she adapted a recent technique which allowed to induce a “hypotonic shock”. She dried the slide after fixation to sufficiently disperse the chromosomes of the dividing cells, thus facilitating their counting. But she added her personal touch: “The tincture I used was my own recipe,” she said of her discovery. Then she saw what the process had revealed: the cells of normal children had 46 chromosomes, but the cells of those with Down’s syndrome had 47.

The second place

However, Gautier was unable to identify this extra chromosome with his old low-resolution microscope. It was then that Jérôme Lejeune, researcher at the National Center for Scientific Research (CNRS) and student at Turpin, offered to have his slides photographed in a better equipped laboratory. Gautier accepted and gave them to him. It was May 1958. The young woman expected an article to be written, but nothing happened. “I did not see the photos: they were, they told me, with the boss, who was not communicative”, wrote Gautier 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 talked about the “French discovery”, photos in hand.

The icing on the cake ? When the article first appeared in January 1959 in Proceedings of the French Academy of Sciences, not only Marthe Gautier had not been informed, but her first name appeared as “Marie” and her surname as “Gauthier”. And this name appeared in second place, 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 scientific scene as the “discoverer” of the first human chromosomal abnormality – which, in 1960, the Denver Conference named trisomy 21. Lejeune devoted the end of his career to the study of this genetic disease, the subject of his thesis in 1961. That same year, he received the CNRS silver medal and, with Turpin, the Jean Toy prize. In 1962, Lejeune discovered trisomy 16. In 1964, he became a professor of genetics. And in 1969, he will receive the William Allan Prize, one of the most prestigious in the field of genetics.

Gautier left this field to devote the rest of his career to pediatric cardiology. “As for me, I felt a moral obligation, and following my deep convictions, I left this path to return to the one who would guide me to focus on the treatment of children with heart disease – an area in which, before this adventure, I had been deeply involved.” And with that, she clearly and simply ended her story.

But even though Gautier didn’t claim credit for getting the ball rolling on the discovery of the extra chromosome, his name wasn’t completely erased from history.

Inserm recognizes Gautier

The controversy began with the story published by The research, excerpts of which can be found in the magazine’s article on Gautier’s death. It 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 Grand Prize from the French Society of Human Genetics at a symposium in Bordeaux when bailiffs showed up, mandate in hand, to ensure, on behalf of Jérôme Lejeune, that his remarks would not harm the reputation of the late doctor. Organizers canceled her event and, in a private ceremony at her hotel, presented the then 88-year-old with her medal.

But it took the intervention of the National Institute of Health and Medical Research (Inserm) to confirm the decisive role that Gautier had played in the discovery. Its ethics committee was tasked with looking into the matter by a group of biologists outraged by the tactics employed by the Jérôme Lejeune Foundation, also known for its anti-abortion arguments. In a opinion published in September 2014, the ethics committee unambiguously took Gautier’s side, stating for all to see that “given the context at the time of the discovery of the additional chromosome, it is unlikely that Jérôme Lejeune’s participation in it was preponderant, if not in its non-conformity”. enhance the training of people (eg Marthe Gautier) which led to their acquisition of expertise (eg in cell culture), a fortiori when combined with a period of time spent outside of France (i.e. in the United States). “There is no doubt that Jérôme Lejeune promoted the discovery, but, as the ethics committee wrote, “this is different from making the discovery. And indeed, “the technical approach is a necessary condition for discovery” — and this is where Marthe Gautier played the “key role”.

To drive the point home, the ethics committee declared: “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 not been systematically associated with this discovery, both in the press and in the awarding of various distinctions.”

Curriculum vitae

Marthe Gautier was born on September 10, 1925 in Montenils (Seine-et-Marne), France. She did her graduate studies in Paris at the faculty of medicine and the faculty of science.

  • Medical student (1946), then intern (1951) at the Hospitals of Paris

  • Graduated in anatomical pathology (1952)

  • Pediatric cardiology dissertation with Robert Debré as thesis supervisor. Thesis subject: “Clinical Anatomo-Pathological Study of Fatal Forms of Bouillaud’s Disease (Acute Rheumatic Disease) due to Beta-Hemolytics Streptococcus Infection” (1955)

  • Researcher, Fulbright Foundation Fellowship, at Harvard University, Harvard Medical School, Boston, Massachusetts, USA (1955-1956)

  • Chief of internal clinic of the service directed by Raymond Turpin, head of the pediatric unit at the Trousseau hospital (1957-1960); creates the first cell culture laboratory in France (1957)

  • Medical attaché in Prof. Nouaille’s new pediatric cardiology department at the Kremlin-Bicêtre hospital (1958)

  • Founder and director of the anatomopathology department for hepatic diseases in children, at the request of Daniel Alagille, director of the Inserm 56 Pediatric Hepatology research unit, at the Kremlin-Bicêtre hospital (1966)

  • Developer and director of the cell culture department (1966)

  • Researcher (1967), then research director at Inserm

  • Counselor at the Hospitals of Paris (1978)

Honors and awards

  • Grand Prize in Human Genetics from the French Society of Human Genetics and the French Federation of Human Genetics for having demonstrated that there are 47 chromosomes in trisomy 21 (2014)

  • Officer of the Legion of Honor (2014)

This article has been translated of the French edition of Medscape.

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