MONOD, JACQUES LUCIEN (1910-1976)

French biologist

French biologist Jacques Lucien Monod and his colleagues demonstrated the process by which messenger ribonucleic acid (mRNA) carries instructions for protein synthesis from deoxyribonucleic acid (DNA) in the cell nucleus out to the ribosomes in the cytoplasm, where the instructions are carried out.

Jacques Monod was born in Paris. In 1928, Monod began his study of the natural sciences at the University of Paris, Sorbonne where he went on to receive a B.S. from the Faculte des Sciences in 1931. Although he stayed on at the university for further studies, Monod developed further scientific grounding during excursions to the nearby Roscoff marine biology station.

While working at the Roscoff station, Monod met André Lwoff, who introduced him to the potentials of microbiology and microbial nutrition that became the focus of Monod's early research. Two other scientists working at Roscoff station, Boris Ephrussi and Louis Rapkine, taught Monod the importance of physiological and biochemical genetics and the relevance of learning the chemical and molecular aspects of living organisms, respectively.

During the autumn of 1931, Monod took up a fellowship at the University of Strasbourg in the laboratory of Edouard Chatton, France's leading protistologist. In October 1932, he won a Commercy Scholarship that called him back to Paris to work at the Sorbonne once again. This time he was an assistant in the Laboratory of the Evolution of Organic Life, which was directed by the French biologist Maurice Caullery. Moving to the zoology department in 1934, Monod became an assistant professor of zoology in less than a year. That summer, Monod also embarked on a natural history expedition to Greenland aboard the Pourquoi pas? In 1936, Monod left for the United States with Ephrussi, where he spent time at the California Institute of Technology on a Rockefeller grant. His research centered on studying the fruit fly (Drosophila melanogaster) under the direction of Thomas Hunt Morgan, an American geneticist. Here Monod not only encountered new opinions, but he also had his first look at a new way of studying science, a research style based on collective effort and a free passage of critical discussion. Returning to France, Monod completed his studies at the Institute of Physiochemical Biology. In this time he also worked with Georges Teissier, a scientist at the Roscoff station who influenced Monod's interest in the study of bacterial growth. This later became the subject of Monod's doctoral thesis at the Sorbonne where he obtained his Ph.D. in 1941.

Monod's work comprised four separate but interrelated phases beginning with his practical education at the Sorbonne. In the early years of his education, he concentrated on the kinetic aspects of biological systems, discovering that the growth rate of bacteria could be described in a simple, quantitative way. The size of the colony was solely dependent on the food supply; the more sugar Monod gave the bacteria to feed on, the more they grew. Although there was a direct correlation between the amounts of food Monod fed the bacteria and their rate of growth, he also observed that in some colonies of bacteria, growth spread over two phases, sometimes with a period of slow or no growth in between. Monod termed this phenomenon diauxy (double growth), and guessed that the bacteria had to employ different enzymes to metabolize different kinds of sugars.

When Monod brought the finding to Lwoff's attention in the winter of 1940, Lwoff suggested that Monod investigate the possibility that he had discovered a form of enzyme adaptation, in that the latency period represents a hiatus during which the colony is switching between enzymes. In the previous decade, the Finnish scientist, Henning Karstroem, while working with protein synthesis had recorded a similar phenomenon. Although the outbreak of war and a conflict with his director took Monod away from his lab at the Sorbonne, Lwoff offered him a position in his laboratory at the Pasteur Institute where Monod would remain until 1976. Here he began working with Alice Audureau to investigate the genetic consequences of his kinetic findings, thus beginning the second phase of his work.

To explain his findings with bacteria, Monod shifted his focus to the study of enzyme induction. He theorized that certain colonies of bacteria spent time adapting and producing enzymes capable of processing new kinds of sugars. Although this slowed down the growth of the colony, Monod realized that it was a necessary process because the bacteria needed to adapt to varying environments and foods to survive. Therefore, in devising a mechanism that could be used to sense a change in the environment, and thereby enable the colony to take advantage of the new food, a valuable evolutionary step was taking place. In Darwinian terms, this colony of bacteria would now have a very good chance of surviving, by passing these changes on to future generations. Monod summarized his research and views on relationship between the roles of random chance and adaptation in evolution in his 1970 book Chance and Necessity.

Between 1943 and 1945, working with Melvin Cohn, a specialist in immunology, Monod hit upon the theory that an inducer acted as an internal signal of the need to produce the required digestive enzyme. This hypothesis challenged the German biochemist Rudolf Schoenheimer's theory of the dynamic state of protein production that stated it was the mix of proteins that resulted in a large number of random combinations. Monod's theory, in contrast, projected a fairly stable and efficient process of protein production that seemed to be controlled by a master plan. In 1953, Monod and Cohn published their findings on the generalized theory of induction.

That year Monod also became the director of the department of cellular biology at the Pasteur Institute and began his collaboration with François Jacob. In 1955, working with Jacob, he began the third phase of his work by investigating the relationship between the roles of heredity and environment in enzyme synthesis, that is, how the organism creates these vital elements in its metabolic pathway and how it knows when to create them.

It was this research that led Monod and Jacob to formulate their model of protein synthesis. They identified a gene cluster they called the operon, at the beginning of a strand of bacterial DNA. These genes, they postulated, send out messages signaling the beginning and end of the production of a specific protein in the cell, depending on what proteins are needed by the cell in its current environment. Within the operons, Monod and Jacob discovered two key genes, which they named the operator and structural genes. The scientists discovered that during protein synthesis, the operator gene sends the signal to begin building the protein. A large molecule then attaches itself to the structural gene to form a strand of mRNA. In addition to the operon, the regulator gene codes for a repressor protein. The repressor protein either attaches to the operator gene and inactivates it, in turn, halting structural gene activity and protein synthesis; or the repressor protein binds to the regulator gene instead of the operator gene, thereby freeing the operator and permitting protein synthesis to occur. As a result of this process, the mRNA, when complete, acts as a template for the creation of a specific protein encoded by the DNA, carrying instructions for protein synthesis from the DNA in the cell's nucleus, to the ribosomes outside the nucleus, where proteins are manufactured. With such a system, a cell can adapt to changing environmental conditions, and produce the proteins it needs when it needs them.

Word of the importance of Monod's work began to spread, and in 1958 he was invited to become professor of biochemistry at the Sorbonne, a position he accepted conditional to his retaining his post at the Pasteur Institute. At the Sorbonne, Monod was the chair of chemistry of metabolism, but in April 1966, his position was renamed the chair of molecular biology in recognition of his research in creating the new science. Monod, Jacob, Lwoff won the 1965 Nobel Prize for physiology or medicine for their discovery of how genes regulate cell metabolism.