François Jacob (1920–2013) French Freedom Fighter Who Helped to Uncover How Genes Are Regulated

COMMENT OBITUARY François Jacob (1920–2013) French freedom fighter who helped to uncover how genes are regulated.

rançois Jacob helped to answer a gene, binds to a cell’s DNA upstream of genetic similarities with humans, mice are question that had been troubling a battery of structural genes that the trio now the models of choice for scientists geneticists for more than 30 years: named the operon. This binding prevents studying human diseases. Jacob’s choice of a Fhow do the various tissues of multicellular the structural genes from being transcribed type of germ-cell cancer to aid research into organisms express different sets of genes into messenger RNA. The model emerged embryonic development in mice proved when all cells contain the same genetic from elegant experiments investigating similarly prescient: the cells studied in his material? Along with two colleagues, Jacob the factors that repress and trigger the laboratory are the ancestors of the stem cells devised the first conceptualization of that are now grown in hundreds of labs gene regulation, opening the door to across the world. the study of development in animals Jacob enjoyed interacting with and humans. people who were different from him, Jacob was born in 1920 in Nancy, but not those who tried to imitate

northeastern France, to a middle-class him, with whom he could be very BETTMANN/CORBIS Jewish family. He studied at the Lycée harsh. When I joined his lab in 1981 Carnot in Paris and went to medical as a postdoc, he gave me total freedom school with the intention of becom- to pursue the questions that I deemed ing a surgeon. His studies were inter- interesting, and this was the same for rupted in June 1940 when, refusing everyone who worked with him. If ever to accept France’s surrender to Ger- we hit on some potentially important many, he escaped to London by boat result, he would jump up in excitement to join the Free French Forces under and ask to see the data. For him, only General Charles de Gaulle. Jacob the science that was moving forward fought for four years as a medical was important. auxiliary in Africa and France. When His immense scientific knowledge, the war ended, he was named a Com- combined with his wartime experi- panion of the Liberation, the highest ences, fuelled a lifelong commitment French military distinction of the to combating racism and preventing Second World War. More than six the misuse of genetics. He presented decades later, he became Chancellor his views on television, radio and in of the Order of the Liberation, the newspapers. He was also a member of order’s most important figure. the French national ethics committee After the war, the injuries that Jacob for the life sciences. had sustained to his arms and legs in Jacob was fascinated with the 1944 prevented him from becoming a history of science and philosophy. surgeon and he worked on producing In his 1973 book The Logic of Life antibiotics for the French army. He heard multiplication of viruses in bacteria, and (Pantheon), he explored the idea that bio- about a scientific revolution taking place those that activate and suppress the synthe- logical knowledge has evolved in successive as a result of physics coming together with sis of the bacterial β-galactosidase enzyme steps, from the study of morphology to that genetics and microbiology. The war and needed to break down lactose into its glucose of the cell, and then to the study of genes and its aftermath had led to a redistribution and galactose components. macromolecules. In several other works, of scientists throughout Europe and the During his early years at the Pasteur such as his 1982 The Possible and the Actual United States, which, combined with the Institute, working with microbiologist (Pantheon), he sought to identify the fea- availability of technologies such as X-ray Elie Wollman, Jacob also proposed a mecha- tures that characterize scientific knowledge diffraction, electrophoresis and electron nism for bacterial conjugation, or mating. In as opposed to other types of knowledge. His microscopy, was spurring a wealth of new this process, part of a bacterial chromosome death marks the end of a golden age of biol- ideas and approaches in biology. Jacob is transferred from a donor bacterium to a ogy, in which members of a relatively small was keen to contribute to these exciting recipient one. In all of these major research international community were free to pur- new developments, and the microbiologist projects, Jacob’s particular skill was being sue whatever question they wanted, with André Lwoff — one of the few French able to conceptualize the molecular mecha- the possibility that they would make huge researchers involved in this new approach nisms underlying complex observations. strides in discovery. ■ — invited Jacob to join his laboratory at the In the late 1960s, Jacob switched to work- Pasteur Institute in Paris in 1950. ing with mice, to align his research with the Michel Morange is professor of biology and Fifteen years later, Jacob was awarded Pasteur Institute’s focus on human disease. director of the Cavaillès Centre (CIRPHLES, the Nobel Prize in Physiology or Medicine It took time to build the genetic-engineering USR 3308) for the History and Philosophy along with Lwoff and Jacques Monod for tools needed to analyse complex organisms of Science at the Ecole Normale Supérieure, describing the ‘operon model’. In this model, and their embryonic development, but Jacob Paris, France. a repressor protein, encoded by a regulatory had made the right decision. Owing to their e-mail: [email protected]