CNRS Senior Researcher Jean Weissenbach's scientific career bears witness to the fact that he is an outstanding geneticist although this self-effacing man that Jean Bernard called "the Vasco de Gama of Science" may not think so. The sixty-two year-old Strasbourg native developed the first high-resolution genetic map of the human genome. Thanks to this tool, which is used as a reference in the field, hundreds of genes linked to genetic diseases have been discovered, making early diagnosis of the diseases possible. He also participated in the bold human genome sequencing project and the development of innovative techniques for exploring the genomes of model biological organisms (fruit flies, rice, and so on). Since 1997, he has been the Director of Genoscope-Centre national de séquençage (CEA, the national sequencing center) and the Joint Research Unit on Metabolic Genomics (Evry University/CNRS/CEA) both on the Genopole campus. Today the laboratory is focussing on the study of microorganisms in ecosystems that are a source of essential biocatalysts for tomorrow's chemistry. Thus starts another great adventure for Jean Weissenbach.
"How can the gene responsible for a given genetic disease be found within the vast territory of the human genome?" For Jean Weissenbach, who produced the first map of the Y chromosome and identified the DNA segment containing the gene encoding the male sex determining factor in 1986 at the Pasteur Institute, the solution was to be found by developing a detailed genetic map. To do so, he used a new type of marker, microsatellites, making it possible to find one's way around the genome. Daniel Cohen, the founder of the Centre d'Etude du Polymorphisme Humain (CEPH, research center on human polymorphism) and 1980 Nobel Medicine laureate Jean Dausset were convinced his idea was relevant and put a laboratory at his disposal.
In 1990, the technique was ready to be deployed on a large scale. The AFM (Association Française contre les Myopathies, the French Association against Myopathy, which organizes the Telethon) decided to fund Jean Weissenbach and Daniel Cohen's genome map projects. In a few months a laboratory was set up in Evry. The Alsace born geneticist took everyone by surprise and put out the first genetic map (published in Nature) at the laboratory called Genethon. His US counterparts were amazed. Thanks to the map whose resolution was improved in 1994 and later in 1996, more than 5,000 markers were located. Teams from around the world started used the map that, within a few months, made it possible to locate more than 700 genes responsible for hereditary diseases, including those to blame for deafness, retinitis, cerebellar ataxia, Chron's disease, hypertrophic cardiomyopathy, and so on. "Success was much greater than I had foreseen," stated Jean Weissenbach.
A Fight for Science and Freedom
The dream of "reading" the entire human genome was born. An international public consortium decided to meet the challenge. The "Human Genome Project" was launched. Each large sequencing center was in charge of one fraction of the genome. In France, Jean Weissenbach's team was assigned sequencing chromosome 14 and started working at the Genoscope. Appointed to the head of the first "major French facility" in biology that he quickly set up in 1997, the French geneticist tackled the gigantic job with enthusiasm, especially as this was a fight for science and freedom. Why? Because the private sector, i.e., US company Craig Venter had entered the race and announced that it wanted to sell the access to the data of human genome sequencing! "We felt that such privatization was very dangerous. Only large private companies would have had access. It would have slowed down science considerably," he felt.
In 2003, Jean Weissenbach and all the researchers at the public consortium managed to finish sequencing the entire genome. The sequencing data was made available to the public as each new piece of information was produced. "We still had to locate the genes within the sequence; which we did by comparing the sequence of the human genome with the genome sequence of the puffer," summarized Jean Weissenbach. His team identified the regions that are preserved during evolution and that, more often than not, contain the genes. The results prompted him to draw up a more realistic estimate of the number of genes in the human genome, i.e., 30,000 instead of the original estimate of 100,000.
Microorganism Study Top of the Agenda
From then on, the researcher decided to "move on from human genetics." Genescope handles (alone or in partnership) the genome sequencing of Arabidopsis (a model plant), Anopheles (a malaria vector mosquito), rice, Paramecium (an unicellular model organism), the grapevine, and also unknown bacteria that are impossible to cultivate. "The biodiversity of microorganisms has a huge amount of information for us," he underscored. That is why for several years now, Jean-Weissenbach has decided to give priority to the study of these microorganisms at Genoscope. His team is studying bacterial communities that live in sludge. "Our goal is to identify new enzyme activities that could be useful for the chemical industry," he explained before adding, "I think that Life Sciences could contribute a lot to chemistry."
