François Jacob at a Cold Spring Harbor meeting, 1953.
François Jacob, 1985.
Barbara McClintock (L) and Jacques Monod (R) at a Cold Spring Harbor meeting, 1946.
(L-R) Jacques Monod, Peter Lengyel, Walter Gibert, Luigi Gorini at a Cold Spring Harbor Meeting, 1966.
Audio Glossary
Enzyme, GeneVideo Interviews
Walter Gilbert is the Carl M. Loeb University Professor at Harvard University. In 1980, he won a Nobel Prize in Chemistry for his work on DNA sequencing.
Clip 1 (0:51)
Before Jacob and Monod, people thought the amount of protein in a cell was constant and proteins turned themselves off.
Clip 2 (0:22)
Jacob and Monod discovered that genes control the amount of protein in a cell.
Clip 3 (0:35)
Where did the idea of negative control come from?
Clip 4 (1:06)
How Jacob and Monod showed the existence of the inhibitor (what Gilbert calls the repressor).
Clip 5 (0:37)
Jacob and Monod never identified the inhibitor, but Gilbert found it.
Clip 6 (0:29)
What we know about gene regulation today.
Clip 7 (0:46)
To explain their data, Jacob and Monod had to hypothesize the existence of mRNA.
Jacques Monod and Francois Jacob were the first to discover how genes were turned on and off. JACQUES LUCIEN MONOD (1910-1976)
Jacques Lucien Monod was born in Paris on February 9, 1910 but he grew up in sunny Cannes, home to the Cannes Film Festival. This may explain why Monod has been described as having an actor's craving for attention. Monod's father, Lucien, was a portrait artist, and his mother, Charlotte Todd, came from Milwaukee, Wisconsin. As a child, Monod climbed rocks, sailed yachts, hunted for fossils, and dissected cats while learning to read Greek and play the cello. By age 16, he decided to become a biologist to explain how living things work in terms that did not violate the laws of physics. Monod returned to Paris in 1928 to study natural sciences at the Sorbonne. He was convinced that genetics held the key to explaining life in these terms. He received his degree in 1931 and started pursuing a Ph.D. During this time, Boris Ephrussi took him to Caltech, the epicenter of genetics. In The Eighth Day of Creation, Ephrussi complained, "I brought him to California to study genetics. He made my life miserable." Though Monod confessed he goofed off in California, he did impress the local residents with his musical abilities. He conducted concerts for American millionaires who tried to hire him for their local orchestra. Monod ultimately rejected a career in music and returned to Paris to finish his degree. In 1938 he married the archeologist Odette Bruhl and, in 1939, became the father of twin boys. In 1940 he received his Ph.D. and joined the French Resistance. During the war, Monod was elevated to the chief of staff of operations for the Forces Françaises de l'Interieur. In preparation for the Allied landings, he arranged parachute drops of weapons, railroad bombings, and mail interceptions. He also continued working with bacteria, the little creatures he could manipulate like chemicals. The work Monod did with bacteria during the war eventually grew into the famous PaJaMo experiment - Arthur Pardee, François Jacob, and Monod's study that showed bacteria make an inhibitor to keep beta-galactosidase production turned off. By the time the lac operon system was worked out, Monod switched his curiosity to allostery. Monod called the concept - in which an enzyme's active site changes shape when it binds an effector molecule - the second secret of life. In the latter part of his career, Monod interpreted the findings of molecular biology for the general public in his book, Chance and Necessity, and directed the Institut Pasteur. Monod died on May 31, 1976 of leukemia; his last words were "Je cherche a comprendre" (I am trying to understand.) FRANCOIS JACOB (1920-)
Francois Jacob grew up in Paris feeling deprived. He wanted a sibling and thought his parents unjustly denied him the accomplice and playmate he was entitled to. He decided to get one for himself but knew they weren't available in stores. He studiously watched kissing couples after hearing that kissing causes a baby to grow in the mother's stomach. He was convinced that the mother had to bite off a fragment of the father but he never witnessed the bloody process he imagined and he gave up. (Jacob later produced four children with his wife Lise in the normal fashion.) As a teenager, Jacob describes himself as "a shade backwards with girls." He didn't have much success with the boys either, constantly getting into fights with right-wing bullies who objected to Jacob's Jewish background. He continued fighting though he rarely won. Jacob excelled in school but he resented the compartmentalization of the subjects. After finishing school, Jacob was attracted to the field of medicine because surgery reminded him of sorcery. The sight of the human body and the religious aspect of the silent operating room transfixed him. Jacob attended medical school until the impending German invasion forced him to flee to England in 1940. In England, Jacob joined General de Gaulle's army, the Free French. He chose artillery, his family's branch, but was forced to move to the medical corps. Jacob served in North Africa and participated in the invasion of Normandy in 1944. The shrapnel that pierced his side during the invasion killed his dream of becoming a surgeon. Nevertheless, he finished medical school after being released from the hospital. To complete school, he searched for a quick and easy thesis project. He studied the properties of a new antibiotic, tryothicin, but describes his research technique as "Charlie Chaplin goes to the lab." Despite his clumsiness and advanced age, Jacob was drawn toward a research career in genetics. Several times Jacob approached Andre Lwoff and his colleague, Jacques Monod, for a fellowship only to be rejected every time. Finally, on Jacob's last attempt, Lwoff was in a good mood and suggested Jacob start work on "the induction of the prophage." Jacob had no idea what this meant but he accepted the project. Jacob emerged from his first seminar on lactose induction dazed but fascinated. The scientists alternately told jokes and grilled each other with tough questions. "This was not the cold, studious, stiff, slightly sad, slightly boring world one often imagines," he recalled in his autobiography. After obtaining his doctorate in 1954, Jacob remained in Lwoff's lab and worked on phage. Jacques Monod worked downstairs on bacteria. After Jacob realized that they were actually studying the same thing - repression - Jacob and Monod began their Nobel Prize-winning collaboration, uncovering the switch that turns beta-galactosidase synthesis off and on. Jacob and Monod's unraveling of the lac operon not only introduced the new concept of regulatory sites on DNA, but also the concept of mRNA. The researchers had to hypothesize the existence of an intermediary molecule between DNA and protein to account for the rapid production of the enzyme's production. Jacob worked with Sydney Brenner during a brief stay in California to verify the hypothesis. | |
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LinksControlling a GeneThis site gives an overview of the lac operon and has experiments that test the lac operon system. This is part of the larger Science Project web site, a collaborative effort between students and teachers. Dr. Francois Jacob -- Quick Time VideoDr. Jacob talks about his experiments. This video clip is from the Zygote web site at Swarthmore College. Infection by E. coliThe E. coli has landed! Watch the bacterium that gave us the lac operon attack an intestinal cell! Click on the link "E. coli's Infection Strategy". Brought to you by the folks at Howard Hughes Medical Institute. Bibliography
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