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François Jacob obituary François Jacob obituary
(5 months later)
François Jacob, who has died aged 92, was awarded the 1965 Nobel prize in physiology or medicine as a result of his perceptive model of gene function in bacteria. Based on meticulous research and put forward jointly with Jacques Monod, it created a new frontier in molecular genetics by establishing the sequential translation and location of individual genes which together endow a bacterium with specific capabilities. Now universally known as the Jacob-Monod model, this first interpretation has since been shown to be substantially correct.François Jacob, who has died aged 92, was awarded the 1965 Nobel prize in physiology or medicine as a result of his perceptive model of gene function in bacteria. Based on meticulous research and put forward jointly with Jacques Monod, it created a new frontier in molecular genetics by establishing the sequential translation and location of individual genes which together endow a bacterium with specific capabilities. Now universally known as the Jacob-Monod model, this first interpretation has since been shown to be substantially correct.
Built upon the hypothesis of the coded helical structure of genetic material, DNA, put forward by Francis Crick, James Watson and Maurice Wilkins, Jacob's scientific work provided the first experimental confirmation of the existence and exacting role of the messenger RNA (mRNA), which carries the negative print of information from the genes to the cell's protein factories (ribosomes) for the production of specific proteins. The cells of living organisms throb with dynamic and complex functions involving many proteins, enzymes and biochemical steps, whose production sequence is critical.Built upon the hypothesis of the coded helical structure of genetic material, DNA, put forward by Francis Crick, James Watson and Maurice Wilkins, Jacob's scientific work provided the first experimental confirmation of the existence and exacting role of the messenger RNA (mRNA), which carries the negative print of information from the genes to the cell's protein factories (ribosomes) for the production of specific proteins. The cells of living organisms throb with dynamic and complex functions involving many proteins, enzymes and biochemical steps, whose production sequence is critical.
This implies an elegantly controlled co-operative triggering of many individual genes which create a sequence of different specific but temporary messenger RNAs that, in turn, are translated into the correct sequence of enzymes needed for a required biochemical process. Jacob set out to unravel these complexities for a single important biochemical change.This implies an elegantly controlled co-operative triggering of many individual genes which create a sequence of different specific but temporary messenger RNAs that, in turn, are translated into the correct sequence of enzymes needed for a required biochemical process. Jacob set out to unravel these complexities for a single important biochemical change.
The scientific search for the "transforming principle" – the specific substance of genetic material – had begun in earnest in the 1930s and had led, for example, to the identification in 1938 of RNA in tobacco mosaic virus by Frederick Bawden and Norman Pirie in the UK. Through laboratory strains of common bacteria, such as pneumococcus, it finally led in 1944 to the identification by Oswald Avery, Colin MacLeod and Maclyn McCarty in America of DNA as the sole genetic material responsible for transforming one strain into another. Parallel work was going on fitfully in wartime Europe, although in France the chosen experimental organism was usually the ubiquitous, large and easily handled gut bacterium, Escherichia coli (E coli).The scientific search for the "transforming principle" – the specific substance of genetic material – had begun in earnest in the 1930s and had led, for example, to the identification in 1938 of RNA in tobacco mosaic virus by Frederick Bawden and Norman Pirie in the UK. Through laboratory strains of common bacteria, such as pneumococcus, it finally led in 1944 to the identification by Oswald Avery, Colin MacLeod and Maclyn McCarty in America of DNA as the sole genetic material responsible for transforming one strain into another. Parallel work was going on fitfully in wartime Europe, although in France the chosen experimental organism was usually the ubiquitous, large and easily handled gut bacterium, Escherichia coli (E coli).
Like many bacterial species, this organism has evolved rapid ways of altering its reproductive method and metabolism to cope with changes in its environment. Among other capabilities, E coli can replicate by sexual conjugation, as well as by simple division, and can switch from glucose to lactose as its primary nutrient. To use lactose it must first break it down into its glucose and galactose components. Jacob exploited these characteristics, first by developing techniques through which to interrupt conjugation at intervals of a few minutes – allowing him to determine the sequence of genes transmitted from one organism to another. Then, using hybrid organisms and experimental transfer from one pure nutrient medium to the other, he mapped the sequence of genes, messenger RNAs and enzymes employed by E coli in the step by step biochemistry of the nutrient switching process which this triggered.Like many bacterial species, this organism has evolved rapid ways of altering its reproductive method and metabolism to cope with changes in its environment. Among other capabilities, E coli can replicate by sexual conjugation, as well as by simple division, and can switch from glucose to lactose as its primary nutrient. To use lactose it must first break it down into its glucose and galactose components. Jacob exploited these characteristics, first by developing techniques through which to interrupt conjugation at intervals of a few minutes – allowing him to determine the sequence of genes transmitted from one organism to another. Then, using hybrid organisms and experimental transfer from one pure nutrient medium to the other, he mapped the sequence of genes, messenger RNAs and enzymes employed by E coli in the step by step biochemistry of the nutrient switching process which this triggered.
This was a tour de force of laboratory skill that carried bacteriology, the still embryonic speciality of molecular genetics and the dynamic details of cellular biochemistry, to new levels of precision. Jacob discovered that in E coli all the genes needed for the nutrient switching process were clustered closely together in the genome as if to facilitate rapid sequential use. With Monod, he coined the name "operon" for such a cluster and, because of their compactness and apparent efficiency, operons were at first thought likely to be universal in living organisms.This was a tour de force of laboratory skill that carried bacteriology, the still embryonic speciality of molecular genetics and the dynamic details of cellular biochemistry, to new levels of precision. Jacob discovered that in E coli all the genes needed for the nutrient switching process were clustered closely together in the genome as if to facilitate rapid sequential use. With Monod, he coined the name "operon" for such a cluster and, because of their compactness and apparent efficiency, operons were at first thought likely to be universal in living organisms.
In essence, this was the research that earned Jacob his Nobel prize – awarded jointly with Monod and André Lwoff – and which, in the context of the prokaryotes (the bacteria and the blue-green algae, now called the cyanobacteria), still stands. But, as molecular genetics and the techniques of gene-mapping widened to embrace more complex organisms (the eukaryotes), it was found that in these the individual genes needed for a specific sequence of biochemical steps are often widely separated and that the same gene may be used in several different and sometimes simultaneous processes. It was also discovered that some RNAs have a much longer lifetime in these organisms than in bacteria.In essence, this was the research that earned Jacob his Nobel prize – awarded jointly with Monod and André Lwoff – and which, in the context of the prokaryotes (the bacteria and the blue-green algae, now called the cyanobacteria), still stands. But, as molecular genetics and the techniques of gene-mapping widened to embrace more complex organisms (the eukaryotes), it was found that in these the individual genes needed for a specific sequence of biochemical steps are often widely separated and that the same gene may be used in several different and sometimes simultaneous processes. It was also discovered that some RNAs have a much longer lifetime in these organisms than in bacteria.
Born in Nancy, north-eastern France, Jacob went to the Lycée Carnot in Paris. When his medical studies were disrupted by the second world war he joined the Free French Forces under General Charles de Gaulle. He served as an officer in Libya and Tunisia and was seriously injured in 1944. After the allied victory, he was awarded the Croix de la Libération and, as a result of his injuries, was unable to fulfil his prewar ambition to become a surgeon.Born in Nancy, north-eastern France, Jacob went to the Lycée Carnot in Paris. When his medical studies were disrupted by the second world war he joined the Free French Forces under General Charles de Gaulle. He served as an officer in Libya and Tunisia and was seriously injured in 1944. After the allied victory, he was awarded the Croix de la Libération and, as a result of his injuries, was unable to fulfil his prewar ambition to become a surgeon.
Instead, after qualifying as a medical doctor at the Sorbonne in Paris in 1947, he turned to research and, within 20 years, had emerged as a world leader in bacterial genetics. He was head of the cellular genetics unit at the Pasteur Institute from 1960 until his retirement in 1991, serving as president of the Pasteur from 1982 to 1988, and was professor of cellular genetics at the College of France from 1965 to 1992. An honorary member of several scientific academies in Europe, he was elected as a foreign member of the Royal Society in London in 1973. In addition to his 200-plus scientific papers, he wrote the books The Logic of Life: A History of Heredity (1970), The Possible and the Actual (1981) and an autobiography, The Statue Within (1987).Instead, after qualifying as a medical doctor at the Sorbonne in Paris in 1947, he turned to research and, within 20 years, had emerged as a world leader in bacterial genetics. He was head of the cellular genetics unit at the Pasteur Institute from 1960 until his retirement in 1991, serving as president of the Pasteur from 1982 to 1988, and was professor of cellular genetics at the College of France from 1965 to 1992. An honorary member of several scientific academies in Europe, he was elected as a foreign member of the Royal Society in London in 1973. In addition to his 200-plus scientific papers, he wrote the books The Logic of Life: A History of Heredity (1970), The Possible and the Actual (1981) and an autobiography, The Statue Within (1987).
He had three sons and a daughter with his first wife, the pianist Lise Bloch, whom he married in 1947. She died in 1983. In 1999 he married Geneviève Barrier.He had three sons and a daughter with his first wife, the pianist Lise Bloch, whom he married in 1947. She died in 1983. In 1999 he married Geneviève Barrier.
• François Jacob, geneticist, born 17 June 1920; died 19 April 2013• François Jacob, geneticist, born 17 June 1920; died 19 April 2013
• Anthony Tucker died in 1998• Anthony Tucker died in 1998
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