Concept 33 Genes can be turned on and off.

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Jacques Monod and François Jacob were the first to discover how genes were turned on and off.

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.