François Jacob

French biologist

• Born: June 17, 1920
• Place of Birth: Nancy, France
• Died: April 19, 2013
• Place of Death: Paris, France

Jacob shared the 1965 Nobel Prize in Physiology or Medicine with André Lwoff and Jacques Monod for their collaborative discoveries concerning the genetic control of enzyme and virus synthesis. These studies were landmarks in the evolving area of molecular biology. Jacob’s work spanned virology, biochemistry, and microbiology.

Early Life

Nobel Prize–winning molecular biologist François Jacob (frahn-swah zhah-kahwb) was born in Nancy, France, the only child of Simon Jacob and Thérèse (née Franck) Jacob. Jacob was reared in the Jewish religion. In his autobiography, he reminisces about the great contrast between his father’s orthodox family and the relaxed Judaism of his mother’s family and its effects on the development of his character.

Simon Jacob, a partner in a prosperous real estate firm, sent his son to excellent schools, beginning with elementary school in Nancy and followed by the Lycée Carnot in Paris. Jacob was an excellent student. However, during this period of his life, he considered himself a loner who had “companions but no friends.” He dreamed fervently of becoming a surgeon, after falling in love with the “race against death and the precision” perceived on viewing an operation. He was encouraged toward this career by a physician uncle, Henri Jacob, and enrolled in the Sorbonne with that goal in mind. With his superb grades, he quickly joined the student elite. Jacob also developed an interest in research from his interaction with his anatomy professor, André Hovelacque. His first love, however, remained surgery.

Jacob’s studies ended abruptly when the German Wehrmacht invaded France. He escaped to London, where he joined the Free French Army in Exile. At first, Jacob was in the artillery. A shortage of doctors led him to join the medical corps, even though he had completed only two years of medical school. Throughout World War II, he saw action all over North Africa as a medical officer with General Paul Leclerc. During the Normandy invasion, he served with the American Second Armored Division.

In 1944, near Le Mans, Jacob was wounded severely while trying to help an injured officer. The resulting hand and arm injuries ended his chances of becoming a surgeon. His valorous war record won for him the French War Cross and the Companion of the Liberation, two of the highest French war medals. Returning to Paris, Jacob had great difficulty in readjusting to civilian life. His family helped him heal mentally and physically during this troubled period. As a result of his intelligence and diligent study, Jacob passed rigorous second-year medical examinations and decided to switch to medicine, after unsuccessful attempts to continue his training as a surgeon. He did well there but felt trapped and briefly attempted careers in freelance journalism, politics, and civil service, yet none of these professions held his interest.

Jacob next became involved in study of the antibiotic tyrothricin at the National Penicillin Center. Bored with medicine and very restless, he developed an interest in a career in biological research. However, at age twenty-eight he considered himself to be too old and perhaps inadequate to meet the challenges of the required career change. Meeting and marrying Lysiane “Lise” Bloch, a concert pianist, in 1947 led him to that career in an interesting way. Conversations with Lise’s cousin, Henri Marcovich, a physician turned biological researcher, led Jacob to realize that he had the ability to go in that direction too. Jacob decided that genetics was the area for him, because it dealt with “quantitative biology” and sat at the “core of things.”

Life’s Work

Jacob’s life’s work may be described as the investigation of the cellular genetics of bacteria. His contributions to the area were many and varied. He began by seeking a research fellowship at the National Research Center and the National Hygiene Institute, where he was rejected by Émile-Florent Terroine and Louis Bugnard, directors of the two agencies. Finally, Jacques Trefouel, director of the Pasteur Institute, offered Jacob a fellowship beginning in October 1949. There he did his doctoral work with the well-known geneticist André Lwoff, whose scientific virtuosity Jacob attempted to emulate.

Jacob bloomed there, in an environment that included frequent encounters with internationally reputed scientists. He completed his PhD thesis, under Lwoff, in 1954. His efforts stemmed from Lwoff’s study of lysogenic bacteria. Such bacteria are not destroyed immediately after infection with bacterial viruses (bacteriophages). However, when they are subjected to external stimuli such as ultraviolet light, lysogenic bacteria are destroyed through multiplication of the viruses in the cell and release of the viral progeny. The overall process is called lysogeny.

Lwoff had shown that the bacteriophages in lysogenic cells initially existed as noninfectious prophages. Jacob’s doctoral research extended understanding of lysogenic bacteria and prophage, carrying Lwoff’s efforts forward. It included the concept that the prophage was hooked into the bacterial chromosome as one of its genetic elements. Jacob later proved this to be correct, but at the time of his thesis defense it was not entirely acceptable to the scientific community.

Immediately after completion of his doctoral thesis, Jacob began collaborating with Elie Wollman in the study of the genetics of bacterial chromosomes. This work was made possible by the discovery that bacteria were sexually differentiated into males and females, which mated by attaching themselves together with a conjugation tube. As soon as this tube forms, the male passes its genetic material through it and into the female.

The experiments that Jacob and Wollman conducted using mating bacteria showed that bacterial chromosomes are circular deoxyribonucleic acid (DNA) molecules, which contained genes arranged in an ordered array that could be mapped experimentally. These chromosomes, attached to the cell membrane, proved always to have their genes arranged in the same consecutive order from this point of attachment. Bacterial variants exhibiting loss of genetic attributes were found to have portions of the chromosome missing. Those exhibiting new genetic characteristics were found to contain additional chromosomal material.

Next, Jacob collaborated with Jacques Monod in the discovery of messenger ribonucleic acid (RNA), making a giant step toward understanding the cellular genetics of bacteria. As a result of their efforts and those of others, it is known that there are three main types of RNA in cells: ribosomal RNA, messenger RNA, and transfer RNA. These RNAs cooperate in protein synthesis, the means by which the hereditary information in the chromosome is actualized. Ribosomal RNAs are structural components of the ribosomes on which proteins are synthesized. Messenger RNAs are copies of genes, and each contains the blueprint for synthesis of a protein. Transfer RNAs carry amino acids, the building blocks of proteins, to the ribosomes.

In their examination of the genetics of protein synthesis, Jacob and Monod also discovered that chromosomal DNA contains structural and regulatory genes. Structural genes are copied to produce messenger RNA blueprints for the production of proteins that cause observed genetic characteristics. Messenger RNAs, produced from regulatory genes, are blueprints for repressor proteins. These proteins combine with chromosomal operator sites and turn off messenger RNA production from structural genes.

Jacob and Monod hypothesized that cellular chromosomes were divided into units called “operons.” An operon is defined as a portion of a chromosome composed of a regulatory gene, an operator site, and several structural genes. The operon hypothesis indicates how cells adapt to environmental changes. Among the phenomena it explains is enzyme induction, the rapid production of enzymes (biological catalysts) needed to respond to a sudden change in the supply of a food (for example the sugar lactose) given to bacteria. Jacob and Monod hypothesized that this process occurred because the food combines with the repressor protein to inactivate it. Repressor protein inactivation was proposed to allow the operon to function well, producing its enzymes via action of its structural genes. The hypothesis stated that when the food was exhausted the repressor protein became functional again and turned off the operon. Numerous repressor proteins have been isolated, and their properties validate the hypothesis.

In the course of this work, Jacob and his colleagues also showed that lysogeny, which had occupied Jacob’s doctoral work, was a result of addition of the viral genome to the chromosome of the host bacteria. This was accomplished by a process that prevented viral replication because of the action of a repressor. Therefore, the reproduction of a bacteriophage in lysogenic bacteria behaved like the expression of an operon. Ultraviolet light and other factors were viewed as the inducers that led to this reproduction and to the destruction of the host cell that followed.

Great things began to happen to Jacob in 1960, when he became chief of the department of cellular genetics at the Pasteur Institute. In 1964, the Collège de France established a chair in cellular genetics for him. Then, in 1965, he shared the Nobel Prize in Physiology or Medicine with Lwoff and Monod, for “discoveries concerning the genetic control of enzyme and virus synthesis,” including the operon hypothesis. This research is viewed by most scientists as the wedge that opened up the field of molecular biology by explaining how genetic information is converted into chemical processes.

Jacob continued to contribute to molecular biology after the prize, completing, developing, and editing important concepts about molecular genetics. Among his major interests was proof of the viral theory of human cancer production. He started investigating cultured mammalian cells and their genetic properties in 1970. Later he turned to the study of early stages of development in the mouse embryo to determinate the regulatory sequence that governs cellular differentiation. From 1982 until 1988 he served as chairman of the board of the Pasteur Institute. Jacob ventured into the public arena in support of science when in 2004 he coauthored a manifesto demanding reform and more funding for science in France and the restoration of scientific positions that had been cut in a cost-saving program. Together with many colleagues, he decried France’s decline from among the world’s leading nations in scientific research.

Jacob was a philosopher of science as well as a scientist. In 1996 Rockefeller University honored him for this popular publications by presenting him with the second Lewis Thomas Prize for writing about science. The award citation recognized him as a “scientist whose voice and visions can tell us of science’s aesthetic and philosophical dimensions.” In particular, the award mentioned his La logique du vivant: Une histoire de l’hérédité (1970; The Logic of Life: The History of Heredity , 1974), Le jeu des possibles: Essai sur la diversité du vivant (1981; The Possible and the Actual, 1982), and his autobiography, La Statue intérieure (1987; The Statue Within, 1988). Philosopher Michel Foucault praised The Logic of Life as “the most remarkable history of biology that has ever been written.” In 1997 Jacob published La Souris, la mouche et l’homme (Of Flies, Mice, and Men , 1998), which considers the broader philosophical implications of molecular biology, such as the use of genetic engineering and the purpose of human life. It also received wide critical and popular accolades.

Throughout his life, Jacob remained a family man; he and Lise had four children, Henri, Laurent, Odile, and Pierre. After Lise died, Jacob married a second time, in 1999, to Geneviève Barrier.

His professional honors included the Charles Léopold Mayer Prize from the Académie des Sciences in 1962 and a silver medal from the Cooperation Center for Scientific Research Relative to Tobacco in 1998. He held membership in such prestigious organizations as the French Academy of Sciences, the Royal Society of London, the Danish Royal Academy of Arts and Sciences, the National Academy of Sciences of the United States, the American Philosophical Society, the Académie Royale de Médicine de Belgique, the Academy of Sciences of Hungary, the Spanish Royal Academy of Sciences, and the American Academy of Arts and Sciences. In 1996 he was elected to the exclusive Académie Française, and he received honorary degrees from several universities.

Jacob died on April 19, 2013, in Paris, France.

Significance

Jacob was always known as a man of probity, an idealist imbued with respect for the law and for honesty, decency, character, and respect for other people. In his autobiography, he attributed these characteristics to his father. He also was recognized as a superb scientist with a love for scientific research. He made exceptional contributions to molecular biology. Working in a defined area, he made it quantitative, where before it was mostly speculative. His efforts greatly enriched the reputation of the Pasteur Institute, helping keep it in the forefront of research in the area. Before the seminal research to which he contributed so greatly, it was not understood how expression of genetic information was accomplished. Although Jacob and Monod have been criticized for initially overgeneralizing their theoretical model to cover all organisms, they provided the basic conceptual approach that led to further research revealing the remarkable diversity and complexity in the regulation of gene activity.

Jacob, as a scientist and as a person, demonstrated bravery and determination. Deprived of his dreams of surgery, he rallied and chose another career in which he not only succeeded but also excelled. Willingness to strive is a lesson he passed on to his students.

Bibliography

Echols, Harrison G. Operators and Promoters: The Story of Molecular Biology and Its Creators. Berkeley: U of California P, 2001. Print.

García-Sancho, Miguel. Biology, Computing, and the History of Molecular Sequencing: From Proteins to DNA, 1945–2000. New York: Palgrave, 2012. Print.

Hirsh, Aaron E. “Shuffle and Deal.” American Scholar 68.2 (1999): 145–49. Print.

Jacob, François. Of Flies, Mice, and Men. Rev. ed. Cambridge: Harvard UP, 2001. Print.

Jacob, François. The Statue Within. New York: Basic, 1988. Print.

Jacob, François, and Jacques Monod. “Genetic Regulatory Mechanisms in the Synthesis of Proteins.” Journal of Molecular Biology 3 (1961): 318–56. Print.

Jacob, François, and Elie Wollman. Sexuality and the Genetics of Bacteria. Rev. ed. New York: Academic, 1961. Print..

Morange, Michel. "François Jacob: Tinkering with Organisms and Models." Outsider Scientists: Routes to Innovation in Biology. Ed. Oren Harman and Michael R. Dietrich. Chicago: U of Chicago P, 2013. 275–90. Print.

Morange, Michel. A History of Molecular Biology. Cambridge: Harvard UP, 1998. Print.

Müller-Wille, Staffan, and Hans-Jörg Rheinberger. A Cultural History of Heredity. Chicago: U of Chicago P, 2012. Print.

Stent, Gunther. Molecular Biology of Bacterial Viruses. San Francisco: Freeman, 1963. Print.

Yardley, William. "Francois Jacob, Geneticist Who Pointed to How Traits Are Inherited, Dies at 92." The New York Times, 16 Apr. 2013, www.nytimes.com/2013/04/26/science/francois-jacob-geneticist-who-pointed-to-how-traits-are-inherited-dies-at-92.html. Accessed 21 Aug. 2024.