In the 1950s, a young doctor named Marthe Gautier happened to be the only scientist in Paris who knew how to grow human cell cultures. Gautier had perfected the new, cutting-edge technique after receiving a highly-coveted scholarship that sent her to study at Harvard University for a year. Upon returning to France, Gautier began working for a pediatric research team, led by Professor Raymond Turpin. With little more than a nod from Turpin, Gautier set up her own lab and designed and conducted experiments that led to the discovery of trisomy 21, the chromosomal anomaly that causes Down Syndrome. Yet, her male colleague, Jerome Lejeune would go on to take credit for the finding, propelling himself into scientific superstardom while Gautier fell into obscurity.
Born in 1925, Marthe Gautier grew up on a farm in a family of 7 children. At a time when most young women aspired to marry and raise children, Marthe’s mother insisted that her daughters receive educations that would give them autonomy and a higher position in society. In 1942, after graduating with honors from a boarding school in Lille, Marthe went to live with her older sister Paulette who was living in Paris.
Already a practicing doctor, Paulette could support Marthe while she pursued her own medical studies. It must have been a difficult time to be a student. Nazi occupiers worked actively to eliminate all professors that were Jewish, freemasons, communists, or in any way opposed to their regime. Tragically, in 1944, just as the end of the war was in sight, Paulette was killed by a stray bullet when a skirmish broke out between German troops and members of the French Resistance. Heartbroken, Marthe clung to her sister’s memory and also to her prophetic words of advice.
« Souviens-toi, nous sommes de simples femmes et, pour réussir, nous devons travailler deux fois plus que les hommes ; en outre, nous sommes issues de parents paysans et nous ne sommes pas filles de patrons. »
“Don’t forget, we are mere women, and to succeed, we have to work twice as hard as men; what’s more, we come from parents who are farmers and we are not the daughters of the boss.”
Off to America
Marthe went on to finish her medical training and complete a residency in pediatric cardiology. She was one of only 2 women who were accepted into her program of 80 students. Gautier’s mentor, Professor Robert Debré, who is considered one of the founders of pediatric medicine, seems to have had a progressive mindset. Impressed by the brilliance of Gautier’s thesis, Debré recommended that Gautier, as well as two of her classmates, receive scholarships to study for one year at Harvard University.
Anxious about traveling so far from home, Gautier boarded a boat in Le Havre in September 1955. Air travel was too expensive for interns living on a shoestring. After a 5-day journey, the ocean liner landed in New York. Gautier headed to Boston where she had 24 hours to find a shared apartment and buy a bed, chair, and table before beginning an intense year of study and hard work.
Gautier was tasked with learning as much as she could about the uses of cortisone in treating heart disease and whether the new drug might be effective in preventing the onset of certain heart conditions. In France, pediatric cardiac surgery was in its infancy. So, Gautier was also expected to learn all that she could about pediatric surgeries taking place in the United States. Upon her return to France, Debré planned to use her to set up a new department for the diagnosis and surgical treatment of various congenital heart conditions.
As if these two objectives were not enough, Marthe was also given a part-time job working as a lab technician in a cell culture laboratory. There, she came to know how to “examine cultures under the microscope, photograph them and develop the photographs” and she explored various new techniques of growing human heart cells for analysis. The technique of growing cells outside of the organism from which they came was not yet known in France. In short order, Marthe surpassed the skills of her co-workers and was appointed head of the lab during her boss’s maternity leave. There’s little doubt that she made the most of her year abroad.
An Unexpected Detour
Upon her return to France, Gautier was disappointed to learn that the post she had been promised in pediatric cardiology before leaving for Boston had been given to one of her colleagues. Instead, she was given another position at the Trousseau Hospital in Paris, working under Professor Raymond Turpin whose research focused on polymalformative syndromes, most notably Down Syndrome. At the time, Turpin believed that chromosomal abnormalities were at the root of this condition. This hypothesis had been advanced as early as 1932 when researchers showed that in pairs of identical twins with Down Syndrome, both twins were affected. Whereas, in cases of fraternal twins, only one of the twins typically exhibited the disorder.
Compared to the more relaxed atmosphere she’d grown accustomed to in the United States, Gautier found her new work environment to be far more rigid, with an aloof Turpin supervising from afar. Making matters worse perhaps was the fact that Gautier had never been a student or intern of Turpin’s so the two didn’t know each other at all. Despite the difficult setting, Gautier needed the job in order to eventually become a respected pediatric cardiologist.
Shortly after Gautier joined his team, Turpin returned from the International Human Genetics Congress in Copenhagen. There, he had learned that researchers in Sweden could now show definitively that humans have exactly 46 chromosomes, arranged in 23 pairs. The prevailing scientific belief had set the number of chromosomes at 48. As early as 1937, Turpin had proposed counting the chromosomes of people with Down Syndrome to see if they had the same number as the general population. However, there had been no way to conduct such an experiment. So, Turpin’s research instead focused on finding patterns in the fingerprints of families affected by the potentially genetic disease.
Now, 20 years later, the ability to grow cell cultures, coupled with certainty about the number of chromosomes in a normal human cell, rendered Turpin’s proposed experiment possible. However, there seemed to be no one in France who knew how to prepare and cultivate cell cultures. Gautier later admitted that she was surprised to realize that she was the only person in Paris that had the expertise necessary to verify Turpin’s long-held suspicions. She revealed her talents to Turpin who agreed to let her pursue this line of research. But, the standoffish department head left her almost completely on her own regarding how to proceed.
Working in a House of Cards
France was still recovering from the ravages of WWII so money to fund research was scarce. The primary focus of French universities at that time was to teach, not conduct scientific studies. Despite the shortages, Gautier tracked down an unused laboratory that was equipped with a refrigerator, centrifuge, and dust-covered microscope dating from the 1920s. With zero budget, she took out a loan of 100,000 anciens francs (roughly $2200 today) to purchase glassware, slides, and other apparatus.
Turpin later emphasized that it was he who made it possible for Gautier to procure fertilized embryos from the Pasteur Institute. This involved a signature, but it was Gautier who regularly needed to traverse the city of Paris to obtain them. Under her own initiative, Gautier bought and raised a rooster (in the hospital garden) from which she withdrew plasma. Normally, the substrate used to grow the cultures relied on embryonic calf’s blood to nourish the cells. Since this proved impossible to obtain, Gautier used her own blood.
Gautier’s notes and subsequent papers clearly show that she was well-versed in all that was known at the time about growing biological tissues inside a laboratory. She explains various techniques that she employed to avoid adverse effects that might alter the fragile chromosomal structure. In order to visualize the strands of chromosomes within each cell, it was important that cells lay side by side on the slides. Otherwise, the strands would overlap and appear like scattered straws of pick-up sticks.
In perfecting her technique, Gautier began by testing the cells of healthy children. While her laboratory was far from ideal, she managed to replicate the experiments of her Swedish colleagues and could see, via her aged microscope, that her sample cells contained exactly 46 chromosomes. Now she began testing cells of children afflicted with Down Syndrome and soon determined that instead of 46 chromosomes, they had 47.
Turpin’s hypothesis had been correct, but it was Gautier’s experiments that led to the discovery of trisomy 21 (in the place of chromosome pair 21, there were 3 chromosomes instead of 2), the cause of Down Syndrome. The breakthrough marks the first time science was able to show a causative link between a chromosomal abnormality and a mental disability.
An Agonizing Silence
While Gautier had been setting up her lab and conducting experiments, Professor Turpin, who had little confidence in her abilities, focused on other projects. Instead of interacting with Gautier directly, he sent his colleague, Jacques Lafourcade, to look in on her precarious undertaking. There is no record of Lafourcade’s observations but soon one of Turpin’s assistants, Jerome Lejeune, began regularly visiting Gautier’s lab. Lejeune had been studying Down Syndrome under Turpin’s tutelage since 1952 and had authored a paper with Turpin after analyzing the fingerprints of people with the disease. Lejeune became interested in Gautier’s work and encouraged her to stay the course.
Now, Gautier’s gamble had paid off but before she and Turpin could publish the results, she would need to obtain images of the abnormal chromosomal count, and Lejeune, her sole enthusiastic supporter, volunteered to help. Lejeune had access to a photo microscope that could document her discovery. In May of 1958, Gautier naively entrusted all of her slides to her ambitious colleague, then waited eagerly to see the resulting photos. When the photos were ready, however, Lejeune said he couldn’t show them to her because he’d given them to Turpin.
Weeks passed with no further word from Lejeune, and Professor Turpin remained extraordinarily hard to contact. Gautier focused her energies on a new job working in a pediatric cardiology ward. She would later write:
« Je suis consciente de ce qui se dessine sournoisement, mais n’ai pas assez l’expérience ni d’autorité dans ce milieu médical dont je n’ai pas encore compris les mécanismes pour savoir comment m’y confronter. Trop jeune, je ne connais pas les règles du jeu. Tenue à l’écart, je ne sais pourquoi l’on ne publie pas tout de suite. Je n’ai compris que plus tard que J.L., inquiet et n’ayant pas l’expérience des cultures, craignait un artéfact qui aurait brisé sa carrière – jusque-là assez peu brillante – mais qui, si les résultats étaient avérés, s’annonçait soudain géniale. Je soupçonne des manœuvres politiques… je n’avais pas tort. En revanche, personnellement, je n’avais pas l’intention « d’exploiter » ce chromosome surnuméraire, ma vie professionnelle se construisait ailleurs, vers la clinique. »
“I was conscious of what was taking place behind my back, but I did not have enough experience or authority in this world of medicine where I didn’t yet understand the mechanisms in place to deal with the situation. I was too young to know the rules of the game. Kept at arm’s length, I didn’t know why they weren’t publishing right away. Only later did I understand that Lejeune, worried and having no experience working with cultures, was afraid I might have introduced an artifact that could ruin his career, which until then had been nothing special, but which, if the results proved accurate, would be seen as brilliant. I suspected political maneuvering and I was not wrong. On the other hand, personally speaking, I had no intention of “exploiting” this additional chromosome, my professional life was headed elsewhere, toward clinical work.”
A Knife in the Back
In August 1958, Lejeune attended the International Congress of Human Genetics held in the bilingual city of Montreal, Canada. Now on the other side of the Atlantic Ocean, Lejeune organized an informal seminar of geneticists to be held in October at McGill University. Before this smaller audience, Lejeune presented Gautier’s methods and discovery as if they were his own, omitting even the name of his longtime mentor, Raymond Turpin. Thereafter, the important trisomy 21 breakthrough, a boon to France’s international scientific standing, would be associated with the name Lejeune.
Back in France, Gautier was still wondering when Turpin planned to publish his department’s findings. She didn’t learn of Lejeune’s announcement in Montreal until November 1958 when he sent her this scrawled note from the United States.
Pasadena, le 5 Nov 58
Ma chère amie,
Chaud merci de votre lettre du 20, à laquelle je réponds avec un inexcusable retard – Mais, vrai! , je n’arrête pas ici – Dans une université loin du bruit, dans une ville où il n’y a rien à voir le travail devient un vice, faute d’alcool!
Un récent mot du patron m’a signalé que vos dernières préparations ont fait l’admiration de Mohr, le généticien norvégien – Cela prouve que ce brave sait apprécier la qualité.
[Ecrit dans la marge:] Prix d’ici à une 15 de jours.
Pasadena, November 5, 1958
My Dear Friend,
Deep thanks for your letter dated the 20th, to which I am inexcusably late in replying. But truly! I never stop here—In a university far from noise, in a city where there’s nothing to see, work becomes a vice, blame the alcohol!
A recent word from the boss tells me that your final preparations have gained the admiration of Mohr, the Norwegian geneticist—This proves that this good fellow knows how to appreciate quality.
[Written in the margin:] Prize within 2 weeks.
Race to the Finish Line
Upon returning to France, Lejeune now felt that time was of the essence. Still working for Turpin, he familiarized himself with the latest advances in genetics. The Scottish researchers, Patricia Jacobs and John Strong had just identified a different extraneous chromosome, in this case, the extra X chromosome that provokes Klinefelter Syndrome in male patients. Suddenly, the need to publish was of the highest urgency. It was imperative that the French team not be surpassed by its Scottish colleagues.
By January 1959, Marthe Gautier had still not been given a chance to look at the pivotal photos. Finally, on a Saturday morning, she received a phone call from Lejeune saying that he was about to present a paper describing their discovery to the Academy of Sciences the following day. In order to assure he’d accurately described her methods, Lejeune hastily read his submission to Gautier over the phone for verification. Although she’d been kept in the dark for more than 6 months, Gautier approved the orally transmitted draft.
At the time, most scientific papers had to undergo peer review by a committee of researchers before they could be published in an international journal. This process often took several weeks to months. In France, however, it was possible to reduce that turn-around time to 3 days. This is the path that Lejeune chose, beating France’s Scottish competitors by 5 days.
The resulting article was co-signed by three authors: Jerome Lejeune, “Marie Gauthier”, and Raymond Turpin. Since Lejeune’s name came first, it was assumed that he was the person who had devised and conducted the crucial experiments. As was customary, Raymond Turpin, the man behind the original hypothesis and director of the lab was cited last. Appallingly, Marthe Gautier’s name did not even appear—instead, Marie in place of Marthe and Gauthier (with an h) instead of Gautier.
The discovery quickly propelled Lejeune to scientific stardom. Responding to journalists from around the world, Lejeune was showered with admiration and respect. Awards were soon to follow, including the Maitre de la recherche medaille d’argent. Proud of his protege, Turpin created a new position for Lejeune, Professor of Cytogenetics. Hailed as “the father of trisomy 21”, the young professor was now well-situated to help usher in a new age of genetic science.
Dedication and Humility Personified
Disgusted by the total lack of respect she’d been shown, Gautier turned away from the field of genetics and devoted the rest of her distinguished career to the care and treatment of children affected by heart disease. For more than 50 years, Gautier’s contributions to the discovery of trisomy 21 went unrecognized. You can find the story of her climb out of obscurity in a follow-up post.
Like so many women that work in technical fields, Gautier found herself without the resources nor the will to stand up to overwhelming male dominance. She counterbalanced the bitter weight of discrimination with the rewards reaped by working on the behalf of others. She reminded herself that she’d never expected a lifetime of award ceremonies and speaking engagements, and moved on. While she did indeed feel cheated, Gautier shrugged off her individual importance, writing of her discovery,
« Première anomalie autosomique humaine ou première anomalie gonosomique, à Paris ou à Edinburgh, ces trouvailles furent faites de façon concomitante, comme c’est souvent le cas quand sont atteints les niveaux scientifiques et technologiques. Si je n’avais été la première, d’autres y seraient parvenus. »
“First human autosomal anomaly or first gonosomal anomaly, in Paris or in Edinburgh, these discoveries were made simultaneously, as is often the case with cutting edge science and technology. If I had not been the first, others would have succeeded.”
Special thanks to my friend and ever-encouraging French coach Mijo Pappas who helped me decipher Jerome Lejeune’s handwriting in the letter he wrote to Marthe Gautier. If you have ideas about Lejeune’s note that differ from the transcription we came up with, please let me know in the comments.
- Tec Review, Marthe Gautier the discoverer of Down Syndrome
- John Hopkins Medicine, Fiftieth anniversary of trisomy 21: returning to a discovery
- The Guardian, Joe Hin Tjio, The man who cracked the chromosome count
- Médecine/Sciences, Cinquantenaire de la trisomie 21
- Histoire de l’INSERM, Marthe Gautier
- france culture, Marthe Gautier, découvreuse de la trisomie 21
- Histoire de l’Inserm, Marthe Gautier
- Le Monde, La mort de Marthe Gautier, découvreuse du chromosome à l’origine de la trisomie 21
- france inter, Marthe Gautier, la découvreuse oubliée
- Le Passeur Éditeur, Les oubliées du numérique
- France Phaleristique, Médaille de la recherche scientifique
- Histoire Normandie, Du Havre à New York : l’épopée des paquebots français (1864-1974)