Sunday, March 9, 2014

Gender, Science, and the Discovery of Trisomy-21 (Down syndrome)

Go to http://xkcd.com/896/ for the full comic. It's good.
Go to http://xkcd.com/896/ for the full comic. It's good.
It's not exactly news that women have often been denied credit for their contributions to major scientific discoveries or inventions. Rosalind Franklin, one of the discoverers of DNA, is justifiably the most famous, and her case still infuriates. Gender bias in the classroom still raises barriers for women who want to become scientists. 

So in honor of woman's history month and one day late for the socialist holiday of International (Working) Woman's Day, I'd like to tell you a story that I've only just learned.

Dr. Marthe Gautier, people seem to agree, was the first to discover the precise genetic basis for Down syndrome. Which is to say she did all the work with very little funding, developed precise samples that demonstrated that people with the syndrome had 47 rather than 46 chromosomes, and lacked the equipment to determine which chromosome it was. Another scientist, Jerome LeJeune, offered to take the samples to another lab with better equipment. Not long after, he became the famous discoverer of Trisomy-21.

You can read a summary of events here in English or this longer piece in French. There's also a .pdf of an essay that Gautier co-wrote on the occasion of the 50th anniversary of the discovery of Trisomy-21, from the journal Human Genetics. From these texts, a few key points emerge:

First - Gautier was practicing what Kuhn would call normal science, building on a new paradigm (DNA) to do the vital work of solving a long-existing process. Second - she was enormously resourceful, using cheap equipment, taking out a loan, raising a rooster for blood cultures and using her own blood for human serum. She made the big breakthroughs here on a shoe-string budget. 

RE : And you also had another regular visitor who seemed intently interested in your project?
MG : Yes, Dr. Jérôme Lejeune. He was in charge of the outpatient clinic for Down syndrome patients at the hospital. He was a researcher, first grade, working under the National Center for Scientific Research (CNRS), the largest governmental research organization in France.
We were about the same age, in our early 30s. I had not known him previously.
Later, I learned that he was a protégé of Prof. Turpin and that the two men, both pediatricians like myself, had collaborated on joint research projects and publications on dermatoglyphics and ionizing radiation studies in connection with suspected genetic disorders.
RE : Did Dr. Lejeune have any skills or training in cell culturing?
MG : None whatsoever. As I noted earlier, Dr. Lejeune's main interest was statistical data in connection with fingerprint patterns [dermatoglyphics] of children with Down syndrome. He had never taken an interest in pathologic studies or in cell cultures.
I counted 47 chromosomes on the first mitoses I obtained from the Down syndrome sample thus revealing the first autosomal chromosome aberration recognized in the cells of the human species – trisomy 21.
After getting the slides showing an extra chromosome:
MG: I didn't have a photo light microscope to identify the 47° small fragment.
RE : Was that when Dr. Lejeune offered to help?
MG: Yes, without a light microscope I could not take photographs of my discovery. Dr. Lejeune volunteered to take my slides to another laboratory and get them photographed. Naïvely, I consented.

RE: Did he ever return the slides with the promised photos to you?
MG: No, never. I never saw them. When I finally asked him where the slides were he told me they were being kept under lock and key by Prof. Turpin.
RE: Tell me about the meeting of the International Human Genetics Conference in Montreal, Canada held in August 1958?
MG: Dr. Lejeune was there as an expert on ionizing radiation representing the CNRS. But he also had in his possession a large amount of data relating to my investigation which he had taken without my knowledge.
Lejeune requested that an informal seminar of geneticists be organized at the Department of Genetics at McGill University at which time he proceeded to announce the discovery of the presence of an additional piece of chromatin in patients with Down syndrome.
RE: Did he mention your name in connection with the discovery?
MG: No. He presented the findings as if they were his own. Henceforth, the discovery would always be associated with his name.
The interview goes on to note the many awards and career advancements promptly showered on LeJeune, his gradual emergence as a right-wing polemicist against pre-natal testing, and his alliance with anti-abortion forces. His reward for all this - an ever-advancing case for beatification in the Catholic Church. Fortunately, Gautier concludes, histories of the study of the syndrome are beginning to revisit the evidence and are giving Gautier the credit she seems to deserve.

I'm not an expert in the science. Perhaps there are elements to the story that I am missing. But it fits with a larger pattern of the ways in which women have had trouble entering the scientific profession, been relegated to subordinate positions within labs or programs, and been denied credit for their work.

No one seems to argue that Gautier, with considerable diligence and ingenuity, developed the samples from which LeJeune made his identification of the chromosomal nature of the cause of Down syndrome.

Moreover, Gautier herself offers some thoughts on the subject, and these seem like a good way to conclude:

MG: Well, since this was the only way to reach the higher levels and open the door to a professorship or department head, I had to persevere. The written examination test papers were labeled only with an identification number, with no name, to ensure anonymity and to prevent favoritism or sex discrimination. However, this was impossible to avoid in the oral examination. Anyway, I succeeded at my fourth attempt. I was 25 and it was in 1950. That year, only two women became interns in Parisian hospitals, versus eighty men. This provided me with four years of experience in eight different pediatric departments. That meant eight different bosses working in different specialties and with very different teaching practices. It was a wonderful experience.

RE: I understand that before Paulette's untimely death when German troops were retreating from Paris in 1944, at the war's end, she gave you some excellent advice on being a woman in a male profession.

MG : You have to remember that when I arrived in Paris, during the war, from the country, I was only 17. I was completely naïve, my entire education having taken place in a Catholic girls school. In any case, Paulette was very adamant about two things. Firstly, she said that girls have to work twice as hard as boys, because we need to be especially brilliant in oral examinations, when we are the most vulnerable because our sex is evident. Secondly, nepotism was as rife in medicine, as it was elsewhere. Our father was a farmer and we had no relatives in the medical profession. So we had no highly placed contacts among the heads of departments who could help us.

We knew we were not the "bosses' daughters," but felt this was no reason not to try and reach the top of our profession. We knew it was a gamble. But of course, we did not reckon with my sister's untimely and tragic death.

This is my own personal story which I am telling you today, but I think it bears witness to the veracity of my sister's convictions concerning the role of women in medicine in the mid-20th century.
I am grateful to Gautier for her work in identifying the nature of Down syndrome. Yes, it's led to a lot of complexity in terms of pre-natal testing and issues relating to abortion, issues I intend to address further in the coming month, but there are even bigger consequences of her work. Much as autism was once linked to frigid mothers (no, really); Down syndrome was linked to maternal syphillis (pdf).

Even today, the first reaction to diagnoses of Down syndrome is usually for the mother to blame herself (which is why genetic counselors are taught to stress the random genetic nature of the syndrome right away).

Thanks to Gautier, we know what Down syndrome is, and thanks to her, we can keep working on what it does, and does not, mean.

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