Jacques Lucien Monod Biography (1910-1976)


The structure of all living matter is determined by the composition of its deoxyribonucleic acid, or DNA, molecule; the discovery in the early 1950s thatthe genetic code carried by DNA is responsible for the shape of all the proteins that make up skin, eyes, hair--all the tissues of life--astounded the scientific community at the time. But how this master plan is carried out, and how its instructions are read and followed by the body, were facts discoveredmuch later by French biologist Jacques Lucien Monod and a small cadre of scientists working with him. Monod and his colleagues postulated, and later demonstrated, the process by which messenger ribonucleic acid (mRNA) carries instructions for protein synthesis from the DNA in a cell's nucleus to its cytoplasm, where the instructions are carried out. Monod and two fellow researchers,Francois Jacob and André Lwoff, won the 1965 Nobel Prize for physiology or medicine.

Monod was born in Paris, on February 9, 1910, to Lucien Hector Monod, a painter and intellectual of Swiss Huguenot descent, and Charlotte Todd (MacGregor)Monod, a Scottish-American from Milwaukee, Wisconsin. At the age of seven, Monod moved with his family to Cannes in the South of France. His parents werevery influential in his education, and Monod later credited his father for his own passionate interest in music, and, later, biology. The young Monod learned to play the cello at an early age, and even during the years he was doing research in molecular biology, he played in and directed a string quartet and a Bach choir. Although Monod later confessed a serious inclination towardsa career in conducting, he also showed an early interest in biology, collecting beetles and tadpoles in the woods around his southern France home. His interest developed further, and he entered the College de Cannes from where hegraduated in the summer of 1928. Monod went on to receive a B.S. from the Faculte des Sciences at the University of Paris, Sorbonne, in 1931. Although hestayed on at the university for further studies, Monod felt that the academiccurriculum at the Sorbonne was deficient and did not reflect contemporary biological research. Therefore, it was through the personal contacts he developed during excursions to the nearby Roscoff marine biology station that Monodreceived his true scientific grounding.

While working at the Roscoff station, Monod met Andre Lwoff, with whom he would establish a life-long collaboration. Lwoff introduced Monod to the potentials of microbiology and microbial nutrition, and these became the focus of Monod's early research. Boris Ephrussi, another scientist working at Roscoff, opened Monod to the importance of physiological and biochemical genetics. AndLouis Rapkine, also a Roscoff contemporary, impressed upon Monod the importance of learning the chemical and molecular aspects of living organisms.

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. Then, in October, 1932, he won a Commercy Scholarship that called him backto Paris to work at the Sorbonne once again. This time he was an assistant inthe Laboratory of the Evolution of Organic Life, which was directed by the French biologist Maurice Caullery at the time. 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? This expedition was a great success and developed in Monod a life-long love for sailing. In 1936 Monod left for the United States with Ephrussi, where he spent time at the California Institute ofTechnology on a Rockefeller grant. His research centered on studying the fruit fly ( Drosophila melanogaster ) under the direction of Thomas HuntMorgan, an American geneticist. Here Monod not only met with refreshingly newopinions, but he also got his first look at a new way of studying science--aresearch style based on collective effort and a free passage of critical discussion. This was in contrast to the rigid, sometimes sterile, attitude amongthe faculty at the Sorbonne. 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 ofMonod's doctoral thesis at the Sorbonne.

This was a time of war in Europe, and despite a medical exemption from military service which allowed him to retain his academic position, Monod joined the French resistance movement. His Sorbonne laboratory became an underground meeting place and propaganda print shop. Thereafter Monod also joined the Franc-Tireurs Partisans and was captured by the Gestapo. He managed to escape andcontinued his underground resistance efforts. Monod is also credited with helping to organize the general strike that led to Paris' ultimate liberation,and he was honored with several military commendations for his efforts.

During this period Monod also continued his pursuit of music, forming a Bachchoir, La Cantate, which he would direct until 1948. In 1938, he met his future wife, Odette Bruhl, an archeologist and orientalist, through the choir. Inthe post-war period Monod served as the laboratory director of Lwoff's Department, and he also became an officer in the Free France Forces. As a member of General de Lattre de Tassigny's staff, he met a number of American scientists. They provided Monod with several scientific journals in which he read articles about the spontaneous mutations of bacteria. Monod later recalled the influence these articles had on the course of his career. He noted that thesejournals in particular, lead him to the study of genetics and later, his research into the structure of DNA.

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 amount of food Monod fed the bacteria andtheir 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 inbetween. 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 aform of "enzyme adaptation," in which the latency period represents a hiatusduring which the colony is switching between enzymes. In the previous decade, a similar phenomenon had been recorded by the Finnish scientist, Henning Karstroem while working with protein synthesis. 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 whereMonod would remain until 1976. Here he began working with Alice Audureau toinvestigate the genetic consequences of his kinetic findings, thus beginningthe 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 timeadapting and producing enzymes capable of processing new kinds of sugars. Although this slowed down the growth of the colony, Monod realized that it wasa necessary process as the bacteria needed to adapt to varying environments and foods to survive. Therefore, in devising a mechanism that could be used tosense 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 would summarize 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, which stated that it was the mix of proteins that resultedin a large number of random combinations. Monod's theory, in contrast, projected a fairly stable and efficient process of protein production which seemedto 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 Francois Jacob and Jacob's team. In 1955, working with Jacob, he began the third phase of hiswork 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 thebeginning of a strand of bacterial DNA. These genes, they postulated, send out messages signalling the beginning and end of the production of a specificprotein in the cell, depending on what proteins are needed by the cell in itscurrent environment. Within the operons, Monod and Jacob discovered two keygenes, which they named the "operator" and "structural" genes. The scientistsdiscovered that during protein synthesis, the operator gene sends the signalto begin building the protein. A large molecule then attaches itself to thestructural gene to form a strand of messenger RNA (mRNA). In addition to theoperon is the regulator gene, which 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 thisprocess, 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 hisresearch in creating the new science. His Nobel prize in 1965 both increasedhis responsibilities and thrust him to the center of a growing limelight inthe field of biochemistry.

Monod's life following the Nobel prize reveals a dramatic shift to the administrative side of scientific research. Elected to the College de France and named chair of molecular biology in 1967, Monod used his influence and fame tobolster the cause of the organized student movement against the academic establishment in France. In 1971 he was offered the directorship of the Pasteur Institute and, on April 15, 1971, he was named director general of the institute. At this time the institute was on the verge of financial collapse, and Monod set aside his research to devote all his efforts to modernize and revitalize the organization. As his administrative duties grew, his research activities rapidly slowed and finally stopped in 1972 after the death of his wife. Not long thereafter, Monod himself fell ill with aplastic anemia. Four years later, with his own death imminent, and having completed only the first phaseof his intended sweeping changes at the institute, Monod returned to his homein Cannes. He died there on May 31, 1976.

His twin sons, Olivier and Philippe, followed him into scientific research, Olivier as a geologist and Philippe as physicist. Monod's list of awards and honors was impressive, and it included the Montyon Physiology Prize, the LouisRapkine Medal, and the Charles Leopold Mayer Prize. He was made a Chevalierde l'Ordre des Palmes Academiques and later an officer in the Legion of Honor. He also received both the Croix de Guerre and the Bronze Star Medal.

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