Marthe Gautier, 96, Dies; Had Key Role in Down Syndrome Breakthrough

Dr. Marthe Gautier, a physician and researcher who had a major role in identifying the cause of Down syndrome but whose achievement was undermined when a male colleague took credit for her work, died on April 30, 2022. She was 96.

Her death, in a retirement home in Meaux, France, though not widely reported at the time, was confirmed by her great-niece Tatiana Giraud. The New York Times, which had prepared an obituary about Dr. Gautier in advance, in 2018, learned of her death only recently.

The disputed research in which Dr. Gautier was involved produced a historic breakthrough: It revealed that people with Down syndrome have an extra chromosome, one of the microscopic strands of DNA and protein that carry a person’s genetic blueprint. Humans have 23 pairs of chromosomes.

Down syndrome is also called trisomy 21, meaning that there are three copies of the 21st chromosome present instead of two.

That discovery, at the Armand-Trousseau Hospital in Paris in 1958, was the first to link an abnormal number of chromosomes to a disorder that causes intellectual disability. More connections between such conditions and aberrant chromosomes were soon found.

Those advances led to the development of tests to diagnose the disorders before birth, making it possible to terminate affected pregnancies in many cases.

Dr. Gautier’s story “starts like a fairy tale and ends like villainy,” said Dr. Jean Kachaner, a former student of hers who is a pediatric cardiologist at the Necker Hospital for children in Paris.

At 25, Dr. Gautier was a brilliant physician with a promising future: Among 80 candidates for sought-after internships at the Paris Hospitals in 1950, she was one of only two women chosen. Outstanding in that role, she was then awarded a scholarship in 1955 to study for a year at Harvard.

Dr. Turpin had long suspected that Down syndrome might be caused by a chromosome abnormality, but lamented that no one in Paris knew how to grow the cell cultures needed to test his theory.

Dr. Gautier told an interviewer in 2013, “It struck me in a rather negative way, that here was a man who had proposed a genetic hypothesis for Down syndrome nearly 20 years before, and yet he had not gone on to pursue his theory.”

Dr. Gautier offered to try — she had become an expert in cell culture at Harvard — and was allowed to proceed. But she was given only primitive lab space and a low-power microscope. She paid for other equipment out of her pocket, drew her own blood to feed the cell cultures and bought a young rooster to bleed periodically for its plasma.

Dr. Gautier saw little of Dr. Turpin, but a protégé of his, Dr. Jérôme Lejeune, who knew nothing about cell culture, frequently visited her lab.

A Eureka Moment

In the spring of 1958, Dr. Gautier’s painstaking efforts paid off. Peering through her microscope at tissue she had cultured from children with Down syndrome, she saw that every cell had an extra chromosome.

“I was alone, but I shouted out, ‘Yes!’” she told New Scientist magazine in 2014.

Dr. Gautier lacked the equipment needed to photograph what she saw, but Dr. Lejeune leaped to her assistance, offering to get the pictures made. She handed over her slides, all exquisitely prepared, and never saw them again.

“I was too young to know the rules of the game,” she wrote.

She was stunned to learn that soon after, at a scientific meeting in Montreal, Dr. Lejeune had described the findings as his own.

Then, to get the results on the record — and to beat other research teams doing related work — he quickly wrote up a brief report for a scientific journal without consulting Dr. Gautier or even telling her about it until a few days before it was published.

Dr. Lejeune listed himself as the first author — a prestigious spot customarily reserved for whoever had done the most important part of the work. He listed Dr. Gautier second, misspelling both her first and last names “by a slip of the pen that I dare not interpret,” she wrote.

Dr. Turpin’s name came last, the position usually given to the senior person who directs or oversees the research.

“I was hurt and suspected a degree of manipulation, having a feeling of being the ‘forgotten discoverer,’” Dr. Gautier wrote.

She, not Dr. Lejeune, she said, had cultured the cells, prepared the slides, looked at them through the microscope and counted the chromosomes. All that would have warranted giving her name primacy on the report, but she made no official protest. Dr. Turpin had agreed to the order of the names, and Dr. Lejeune was known to be a favorite of his.

Challenging authority could derail a career, especially that of a young woman trying to make her way in the male-dominated sciences of that era, particularly in France.

After the publication, Dr. Gautier wrote, Dr. Lejeune was “showered with all kinds of awards” without sharing them, including the Kennedy Prize, bestowed by a Kennedy family foundation for outstanding research in the field of intellectual disabilities. President John F. Kennedy personally presented it to him in 1962.

The story was strikingly similar to that of Rosalind Franklin, another female scientist who had been marginalized by ambitious men, this time in Britain. Dr. Franklin took detailed X-ray photographs of DNA that a male colleague, Maurice H.F. Wilkins, gave to James D. Watson and Francis H.C. Crick without asking her. The pictures, which they used without her knowledge, enabled them to determine DNA’s double-helix structure. Dr. Watson and Dr. Crick did not include her as an author of their 1953 landmark scientific paper on the subject.

They and Dr. Wilkins won a Nobel Prize for the DNA work in 1962. (Dr. Franklin would not have been eligible for the Nobel because she died in 1958; the prize is not given posthumously.)

Both the Franklin and Gautier episodes were examined by Dr. Peter Harper, a professor of human genetics at Cardiff University in Wales, who wrote extensively about the history of the field.

“Undoubtedly, Lejeune’s conduct was appalling,” he said in a telephone interview for this obituary in 2018. (Dr. Harper died in 2021.) He added that eminent geneticists in Paris generally agreed that “Marthe Gautier was the principal person, but she was sort of elbowed out of the way by Lejeune as a forceful, dynamic character, and she never got proper support by Turpin.”

Setting the Record Straight

Dr. Lejeune went on to make important discoveries in genetics and to advocate for proper care for children with Down syndrome. He opposed abortion and the prenatal testing that could lead to it. He died in 1994, and his obituary in The New York Times gave him sole credit for finding the cause of Down syndrome. A foundation started by his family mentions Dr. Gautier and Dr. Turpin on its website but says that Dr. Lejeune made the discovery.

The foundation has also tried to have Dr. Lejeune declared a saint by the Roman Catholic Church. In 2021, Pope Francis bestowed the title “Venerable” on Dr. Lejeune in recognition of his “heroic virtues,” a step in the process of attaining sainthood.

For years, friends and colleagues had urged Dr. Gautier, who had never spoken publicly about Dr. Lejeune’s conduct, to set the record straight. She told them that she had written an essay about the episode but that it was to be published only after her death.

But as 2009 and the 50th anniversary of the Down syndrome publication approached, she found that she could no longer keep silent. The notion of Dr. Lejeune’s being made a saint may have been the last straw, said Dr. Simone Gilgenkrantz, a friend and fellow geneticist.

In 2009, Dr. Gautier’s “personal testimony” was published in a French scientific journal. An English version, translated by Dr. Harper, was published in Human Genetics.

The Lejeune Foundation has challenged her account, stating on its website, “There is not a single shred of evidence to support the charges made against Lejeune.” It also says that handwritten statements in his notebook indicate that he saw the extra chromosome first.

Dr. Harper was unpersuaded. “Gautier did all the initial work and most of the subsequent work,” he said. “There’s a sort of slight gray zone as to whether Lejeune did anything significant.”

He added, “What he did other than get the photographs done, it’s impossible to be sure.”

Dr. Gautier became a cause célèbre among doctors and scientists in Europe. In 2009, the Armand-Trousseau Hospital mounted a plaque to honor the Down syndrome finding, listing Dr. Gautier first, then Dr. Lejeune and Dr. Turpin.

Doctors and researchers also contacted the Catholic Church to challenge Dr. Lejeune’s prospective sainthood, asserting that he had publicly misrepresented himself as the sole discoverer of trisomy 21.

In 2014, the French Federation of Human Genetics gave Dr. Gautier a medal to honor her for the Down syndrome discovery. She was invited to give a speech at a meeting of the group in Bordeaux, in which she planned to tell the whole story.

But the event became a fiasco. Just a few hours before she was to speak, her talk was canceled. Legal representatives of the Lejeune Foundation had arrived with a court order allowing them to record her speech as evidence in case she damaged Dr. Lejeune’s reputation. The genetics group, fearing a lawsuit, called off her talk and gave her the award a day later in a private ceremony.

The attempt to silence Dr. Gautier only drew more attention to her story. The newspaper Le Monde published a scathing article, critical of the genetics federation for backing down. The prominent journals Nature and Science also published news articles recounting the contentious history.

The genetics group later said it regretted the cancellation, and many members considered it a disgrace.

“The organizers asked me not to speak to avoid legal problems,” Dr. Gautier told New Scientist. “But I should have refused and given my talk anyway.”

A Daughter of Farmers

Marthe Gautier was born on Sept. 10, 1925, in the Île-de-France region, not far from Paris. Her parents were farmers, and she was the fifth of seven children.

In 1942, when she was 17, Marthe followed her elder sister, Paulette, to study at the Faculty of Medicine of Paris, which was then part of the University of Paris. With the city occupied by Nazi Germany, Paulette was killed by stray gunfire in 1944 during a clash between German troops and members of the French Resistance.

Rather than fight for the credit due her after the Down syndrome discovery, Dr. Gautier left genetics research and returned to the field that had been her first love: pediatric cardiology. She had a long, illustrious career at Bicêtre Hospital in Paris, where she treated children with rheumatic fever and infants with heart defects; helped to develop diagnostic procedures for pediatric heart disorders; worked with surgeons to devise operations to repair heart defects; and trained generations of doctors.

In 1967, while still working at Bicêtre, she became director of research at INSERM, the French National Institute of Health and Medical Research, where she led a research program on pediatric liver disease.

Dr. Kachaner said Dr. Gautier was among the founders of pediatric cardiology. And yet, he noted, because she was a woman, she was not even allowed to apply to become head of her department at Bicêtre.

She retired in 1990 at 65. She is survived by many nephews and nieces.

Dr. Gautier wrote that she never forgot an admonition her sister Paulette had given her: “If you’re a woman, and you’re not the boss’s daughter, you have to be twice as good to succeed.”

Stella Raine Chu and Ash Wu contributed reporting and Alain Delaquérière provided translations.