Jacques Lucien Monod

1910-1976

French Geneticist

In 1965 Jacques Lucien Monod shared the Nobel Prize in Medicine with François Jacob (1920- ) and André Lwoff (1902- ) for their contributions to discoveries concerning the genetic regulation of enzymes and viral synthesis. In 1961 Monod and Jacob proposed the concept of messenger RNA and the operon theory.

Monod was born in Paris. His father was a French artist and his mother was an American. Monod studied zoology at the Université de Paris (Sorbonne). He earned his B.Sc. in 1931 and his doctorate in 1941. In 1936 he worked in the laboratory of Thomas Hunt Morgan (1866-1945) at Caltech. During World War II, Monod was involved in the French Resistance. He served as a professor at the Université de Paris until 1945, when he moved to the Pasteur Institute, where he spent the rest of his scientific career. He became head of the Department of Cellular Biochemistry in 1953 and director of the Institute in 1971.

As a student, Monod was fascinated by the new science of genetics, but his early researches involved the problem of growth in bacteria. His doctoral dissertation involved quantitative studies of the factors that govern the rate of growth of bacterial cultures. Monod noticed that when bacteria were grown with certain sugars in the medium, the initial growth phase was followed by a lag phase, and then another growth spurt. In 1940 Lwoff suggested that this growth pattern might be the result of enzyme adaptation, or induction. Monod began to think that his studies of inducible enzymes and bacterial growth might be linked to the new work on bacterial mutants reported by Salvador Luria (1912-1991) and Max Delbruck (1906-1981). Studies of the enzyme ß-galactosidase in a mutant strain of bacteria indicated that enzyme induction involved the synthesis of new protein molecules. Monod speculated that a mutation in the adaptive function of an enzyme might be the result of prior mutations in the gene. Experiments carried out by Monod and his colleagues suggested that the biosynthesis of enzymes was stimulated by the presence of an "inducer." In most cases, the inducer seemed to be the substrate of the enzyme.

A series of experiments carried out by Jacob and his colleagues between 1958 and 1963 led to the "operon theory," a theoretical framework linking gene expression and the induction of enzyme synthesis. The operon was assumed to be a fundamental unit of bacterial gene expression and regulation, consisting of structural genes, regulator genes, and control elements. Genes were assumed to play two essential roles: encoding protein structure and regulating protein synthesis. According to Jacob and Monod, gene expression is made possible when an inhibitor, called the "repressor," is removed from the gene. This leads to the biosynthesis of an inducible enzyme. The classic experiment that supported the operon theory became known as the "PaJaMo experiment," in honor of Arthur Pardee (1921- ), Jacob, and Monod, who published the results of the experiment in 1959 in the Journal of Molecular Biology.

Another important contribution to enzyme control mechanisms made by Monod is known as the theory of allosteric regulation. In 1961 Monod suggested that interactions between enzymes and small molecules, such as substrates, activators, and inhibitors, might change the shape of the enzyme in ways that would affect its activity and affinity for its substrates.

Both Jacob and Monod wrote eloquently about science, life, and philosophy. In Chance and Necessity (1970) Monod noted that biology was sometimes accorded only a marginal place among the sciences, because the study of living things on earth did not seem to lead to universal, cosmic laws. He argued that the ultimate aim of science was to clarify the relationship between human beings and the universe; therefore, biology deserved a place at the center of the sciences. The main thesis of his philosophical essay Chance and Necessity was that life arose by chance and that all species of life, including human beings, were ultimately the products of random genetic mutations. Monod was a gifted musician, a sailor and rock-climber, an opponent of Lysenkoism and other forms of pseudoscience, and a supporter of women's rights and educational reform.

LOIS N. MAGNER