Francois Jacob, a Nobel Prize-winning French scientist who was a co-discoverer of the mechanism for gene regulation, which determines a cell’s specific function and characteristics, died April 19 in Paris. He was 92.
The French government announced his death, but further details were not immediately available.
Dr. Jacob served in the French Resistance during World War II, and his injuries prevented him from achieving his dream of becoming a surgeon. He turned to biological research and eventually shared the 1965 Nobel Prize in Physiology or Medicine with two colleagues at the Pasteur Institute in Paris, Jacques Monod and Andre Lwoff.
They were among the founding generation of molecular biologists who discovered how genes work in the years immediately after James Watson and Francis Crick’s publication of the structure of DNA in 1953 — 60 years ago this week.
Every cell with a nucleus contains a complete copy of all of the organism’s genes — its genome. Only a tiny fraction of those genes are active in any cell, and the particular genes that are active give the cell its “personality.” Liver cells have a different suite of activated genes compared with bone cells or brain cells, for instance.
Dr. Jacob and Monod showed how a gene’s activity can be turned on and off. That activity, known as “gene regulation,” is the secret of life’s complexity and adaptability.
“If you look at the DNA of any organism,” said David Baltimore, a professor at the California Institute of Technology and winner of the 1975 Nobel Prize in Physiology or Medicine, “it tells us nothing about how specificity of function is developed in each and every cell of our body. That requires regulation. What Jacob and Monod did was tell us where and how that regulation occurred.”
As a young scientist, Baltimore spent a year at the Pasteur Institute studying in the lab of Lwoff, who had once directed Dr. Jacob’s research.
“My generation recognized that what they were doing is leading the world to the future,” said Baltimore, who is 75.
Dr. Jacob and Monod’s most famous experiments explained how the bacterium Escherichia coli is able to adapt to changes in the available food in its environment.
The bacterium’s preferred food source is glucose. But if put in a culture in which the only source of energy is a different sugar called lactose, the cells will start consuming it. To do that, it needs to produce three specific enzymes.
The two scientists showed that when lactose is abundant, a lactose molecule attaches to a protein that is “repressing” the three enzymes’ genes. The genes are then activated, which allows the cell to consume lactose and survive.
The entire complex is called the lac operon. It is a model of coordinated gene regulation that, in many varieties, gives cells their particular functional characteristics.
Dr. Jacob, Monod and other collaborators also were instrumental in showing that messenger RNA (mRNA) is the intermediary that carries the transcribed information from a gene’s DNA to cellular workshops called ribosomes, where that information is “translated” into proteins.
“He was a prime mover in many of the most fundamental discoveries of molecular biology,” Matthew Meselson, a Harvard biologist who once collaborated with Dr. Jacob, said Tuesday. “He was a hero. A giant.”
Francois Jacob was born June 17, 1920, in Nancy, France. He was studying medicine in Paris when World War II broke out.
He joined the French Resistance as a medical officer in 1940 and fled France for England by boat just before the Nazis seized the country.
He was wounded in Tunisia, then joined French forces in Normandy soon after D-Day in 1944 and was severely wounded in his right arm and leg in a grenade attack. He spent seven months in a hospital.
He received the Legion of Honor, Croix de Guerre and many of France’s highest decorations for serving in the resistance movement.
After the war, Dr. Jacob continued his medical studies at the Sorbonne in Paris, graduating in 1947. Because of his wartime injuries, he turned to biological research, joining the Pasteur Institute in 1950.
As an assistant to Lwoff, Dr. Jacob worked in such tight quarters that their laboratory was nicknamed “the attic.”
Dr. Jacob received bachelor’s and doctoral degrees in biology from the Sorbonne in 1951 and 1954, respectively. In the late 1950s, he began working with Monod at the Pasteur Institute.
After the Nobel was presented in 1965, the American Cancer Society issued a statement saying the work of the three French scientists “is an inestimable contribution to our knowledge of life processes, the riddle of growth and heredity.”
Months after winning the Nobel, Dr. Jacob and his two colleagues were part of a rebellion at the Pasteur Institute that ousted the director and the governing board. Dr. Jacob served as chairman of the institute from 1982 to 1988.
Other experiments by Dr. Jacob showed that bacteria can evolve through mutation, permitting them to survive in hostile environments. This phenomenon explains how bacteria can sometimes become permanently resistant to antibiotics.
Later in his career, he focused on the embryonic development of mice and published several books, including one examining the history of science, “The Logic of Life,” and another, “The Possible and the Actual,” about evolution.
Dr. Jacob had four children with his first wife, pianist Lysiane Bloch. After her death, he married Genevieve Barrier in 1999. Complete information about survivors could not be confirmed.
Dr. Jacob also published an autobiography, “The Statue Within.”
“I am bored with what has been done,” he wrote in the book, “and excited only by what is to do.”