Once upon a time Down Syndrome – The Story of the discovery


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« There is only one thing left I can do to save them : cure them. The task is great but so is hope ; we will find a way. It is impossible not to. It is a much less difficult intellectual effort than sending a man on the moon. »

 Jérôme Lejeune

Professor Jérôme Lejeune was a man inhabited by the mind of a scientist, in a good sense, meaning a curious and inventive mind. These are the qualities which explain why his name was put forward, without any contest, as the first person to have described the first chromosomal anomaly related to a pathology – Down Syndrome-.

These scientific qualities made him a pioneer in terms of chromosomal research, digging always deeper into this new field of cytogenetics he was helping to create and in which he left his mark.

The circumstances of the discovery

First, let’s rapidly go over the circumstances in which the discovery was made: in 1952, the young Jérôme Lejeune has just finished his military service and is looking for a job. That is when Professor Raymond Turpin (1852-1988), who sees in Jérôme Lejeune a young talented doctor, invites him to join his paediatric unit at the Trousseau hospital. Professor Turpin names Jérôme Lejeune research trainee at the CNRS (France’s national scientific research centre) and, in 1953, reassigns him to his team to care for mongol children. .

Dr. Jérôme Lejeune’s entry in Pr. Raymond Turpin’s team and his collaboration with Marthe Gauthier in that laboratory were decisive for his career because Pr. Turpin was interested in genetics and in Down Syndrome, and had made the hypothesis of a link between mongolism and a chromosomal anomaly. By studying the Mongol children’s dermatoglyphics they deduced that the anomaly had to occur as soon as the embryo was constituted, which favoured the theory of a link between mongolism and a chromosomal alteration.

Marthe Gauthier, who learned about the techniques of cell culture in the US, has just entered (1956) Professor Turpin’s service as a clinical director.

She knows how to prepare the cell cultures (fibroblasts) of mongol children, which are necessary for this study and how to apply the Rothfields and Siminovitch’s hypotonic shock technique which enables the dispersion of the chromosomes and their visualisation.

She shares the photographs of these chromosomes with Jérôme Lejeune. Studying these photographs, Jérôme Lejeune starts to count down the number of chromosomes in the cells.

Lejeune count

47 !

The analysis notebook he started on July 10th, 1957 indicates that he managed for the first time, on May 22nd, 1958, to identify on a mongol child the Presence of 47 chromosomes instead of the usual 46.

This anomaly is due to the Presence of an additional chromosome on the 21st pair. Thus, at 32 years old, by identifying the additional chromosome in the fibroblasts’ nucleus of a mongol child, Jérôme Lejeune had just made a discovery of historical importance of which even he still didn’t understand the full impact.

For the first time in the history of genetics, a link was thus established between a mental disability and chromosomal anomalies. This discovery was the starting point of the great cytogenetic adventure.

On June 13th 1958, Jérôme Lejeune once again found this additional chromosome in the cells of another mongol child. He presented the photograph of this Karyotype to the International Congress of Genetics at Montreal. However, it only generated very little interest, if not a sceptical reaction.

This discovery was communicated to the medical world on January 26th, 1959.

That day, Jérôme Lejeune, Marthe Gauthier, and Raymond Turpin, in this order of authors, present to the Academy of Sciences a study on “tissue culture of human chromosomes” in which they report a normal diploid number of 46 chromosomes in 6 boys and 2 non-mongol girls, whereas in three mongol boys the number of chromosomes found is 47, “because of the presence of a little additional chromosome, the 21st”, which also makes the sex diagnosis impossible. Jérôme Lejeune is the first author of the presentation, which implies that he is the author of the discovery. Marthe Gauthier comes second and Raymond Turpin third, according to the standard Practice of any head of laboratory; this does not automatically imply a direct participation of all three in the discovery, even though in this case it does.

On March 16th, 1959, another note, by the same authors and in the same order, will again be presented to the Academy of Sciences, confirming the first publication and this time describing the presence of the 47th chromosome in mongol children.
From then on the scientific community understood the importance of this discovery and acknowledged Jérôme Lejeune as the first author of these notes and the discoverer of Down Syndrome. Marthe Robin, second author of the note, is however seen as the person who made it technically possible.
The recognition of the primordial part played by Jérôme lejeune in the discovery of Down Syndrome in children affected by mongolism did not actually arouse any objections. In particular, neither Raymond Turpin nor Marthe Gauthier denied it.

The attribution of the authorship of the discovery of what will now be called “Down Syndrome” to Jérôme Lejeune (first author of the study) has never been contested. It is only latter on, in 1977, that Raymond Turpin tried to claim the authorship of the discovery without, however, expressing any claim or accusing Jérôme Lejeune. And it is even later, in 2009, year of the 50th anniversary of the discovery of Down Syndrome, that Marthe Gautier will start rewriting the story to put forward her role in the discovery of 1959.

Recognition of the importance of Jérôme Lejeune’s discovery

The discovery made by Jérôme Lejeune of the relationship between Down Syndrome and mongolism rapidly had a huge impact, because it kick-started a whole new research on the chromosomal origins of various congenital conditions, before being further developed and used also in research on the genetic origin of many pathologies. It is this discovery that opened the way to a  new science called cytogenetics, based on the study of the Karyotype of individuals (standard pattern of the whole of the chromosomes of a cell, study through a microscope) and which exponential development helped to recognize the chromosomal origin of many congenital diseases.

The importance of this discovery, and the primordial part he played, were in fact recognized at an international level through the attribution of prestigious awards, of which the William Allen Award, to Pr. Jérôme Lejeune, and to him only. The day after he died, Jean de Grouchy, who wrote an article in his memory, once more recognized him as the uncontested discoverer of Down Syndrome.

The drama for Jérôme Lejeune

The tragedy for Jérôme Lejeune was to see his discovery used for the opposite reasons for which he had made it.

Jérôme Lejeune was hoping, that once he found the chromosomal origin of the lack of cognitive development in people with Down Syndrome, he could develop a therapeutic treatment which would enable to reduce this cognitive disability or even neutralize it. People chose to take advantage of the possibility of diagnosing Down Syndrome, which was made possible by Jérôme lejeune’s Discovery, and used it in the easiest and most harmful way possible: destroy children with Down Syndrome in their mother’s womb.

It is only recently that, thanks to the Progress made in genic therapy concerning the silencing of certain genes, we started trying to treat the patients by silencing the genes of the additional chromosome. This research work makes us hope that one day it will be possible to treat an embryo affected by Down Syndrome.

The discovery of Pr. Jérôme Lejeune will then have found its positive outcome after having been used, for years, to hunt Down Syndrome down and eliminate it.

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