François Jacob (; 17 June 1920 – 19 April 2013) was a French
biologist who, together with
Jacques Monod, originated the idea that control of
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
levels in all
cells occurs through regulation of
transcription. He shared the 1965
Nobel Prize in Medicine with
Jacques Monod and
André Lwoff.
Early years
Jacob was born the only child of Simon, a merchant, and Thérèse (Franck) Jacob, in
Nancy, France. An inquisitive child, he learned to read at a young age. Albert Franck, Jacob's maternal grandfather, a four-star general, was Jacob's childhood role model. At seven he entered the
Lycée Carnot, where he was schooled for the next ten years; in his autobiography, he describes his impression of it: "a cage". He was antagonized by rightist youth at the Lycée Carnot around 1934. He describes his father as a "conformist in religion", while his mother and other family members important in his childhood were
secular Jews; shortly after his
bar mitzvah
A ''bar mitzvah'' () or ''bat mitzvah'' () is a coming of age ritual in Judaism. According to Halakha, Jewish law, before children reach a certain age, the parents are responsible for their child's actions. Once Jewish children reach that age ...
, he became an
atheist.
Though interested (and talented) in physics and mathematics, Jacob was horrified at the prospect of spending two additional years in "an even more draconian regime" to prepare for higher study at the
Polytechnique. Instead, after observing a surgical operation that cemented his "slight interest" in medicine, he entered medical school.
During the German occupation of France—and on the heels of his mother's death—Jacob left France for Great Britain to join the war effort. Jacob, who had only completed his second year of medical studies, joined the medical company of the
French 2nd Armored Division in 1940. He was injured in a German air attack in 1944 and returned to now-
liberated Paris on 1 August 1944. For his wartime service, he was awarded France's WWII highest decoration for valor, the
Cross of Liberation, as well as
Légion d'honneur
The National Order of the Legion of Honour ( ), formerly the Imperial Order of the Legion of Honour (), is the highest and most prestigious French national order of merit, both military and Civil society, civil. Currently consisting of five cl ...
and
croix de guerre.
After his recovery, Jacob returned to medical school and began researching
tyrothricin and learning the methods of
bacteriology
Bacteriology is the branch and specialty of biology that studies the Morphology (biology), morphology, ecology, genetics and biochemistry of bacteria as well as many other aspects related to them. This subdivision of microbiology involves the iden ...
in the process. He completed a thesis he described as "replicating American work" on the effectiveness of the antibiotic against local infections, and became a medical doctor in 1947. Though attracted to research as a career, he was discouraged by his own perceived ignorance after attending a microbiology congress that summer. Instead, he took a position at the Cabanel Center, where he had done his thesis research; his new work entailed the manufacture of an antibiotic,
tyrothricin. Later, the center was contracted to convert gunpowder factories for penicillin production (though this proved impossible).
Also in this period, he met and began courting his future wife, Lise Bloch. Jacob remarried in 1999 to Geneviève Barrier.
Research
In 1961 Jacob and Monod explored the idea that the control of
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
expression levels in cells is a result of regulation of
transcription of
DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
sequences. Their experiments and ideas gave impetus to the emerging field of molecular
developmental biology
Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of Regeneration (biology), regeneration, asexual reproduction, metamorphosis, and the growth and di ...
, and of
transcriptional regulation in particular.
For many years it had been known that bacterial and other cells could respond to external conditions by regulating levels of their key
metabolic
Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the ...
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s, and/or the activity of these
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s. For instance, if a bacterium finds itself in a
broth
Broth, also known as bouillon (), is a savory liquid made of water in which meat, fish, or vegetables have been simmered for a short period of time. It can be eaten alone, but it is most commonly used to prepare other dishes, such as soups ...
containing
lactose
Lactose is a disaccharide composed of galactose and glucose and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from (Genitive case, gen. ), the Latin word for milk, plus the suffix ''-o ...
, rather than the simpler sugar
glucose
Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
, it must adapt itself to the need to 1) import lactose, 2) cleave lactose to its constituents glucose and
galactose, and 3) convert the galactose to glucose. It was known that cells ramp up their production of the enzymes that do these steps when exposed to lactose, rather than wastefully producing these enzymes all the time. Studies of enzyme activity control were progressing through theories of the (allosteric) action of small
molecule
A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
s on the enzyme molecule itself (switching it on or off), but the method of controlling the enzyme production was not well understood at the time.
With the earlier determination of the structure and central importance of
DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
, it became clear that all proteins were being produced in some way from its genetic code, and that this step might form a key control point. Jacob and Monod made key experimental and theoretical discoveries that demonstrated that in the case of the lactose system outlined above (in the bacterium ''
E. coli''), there are specific proteins that are devoted to repressing the transcription of the DNA to its product (
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
, which in turn is
decoded into
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
).
This repressor (the
lac repressor) is made in all cells, binding directly to DNA at the
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s it controls, and physically preventing the transcription apparatus from gaining access to the DNA. In the presence of lactose, some of the lactose is converted to allolactose, which binds to the repressor making it no longer able to bind to DNA, and the transcriptional repression is lifted. In this way, a robust
feedback loop is constructed that allows the set of lactose-digesting proteins products to be made only when they are needed.
Jacob and Monod extended this repressor model to all genes in all
organism
An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...
s in their initial exuberance. The regulation of gene activity has developed into a very large sub-discipline of
molecular biology
Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
, and in truth exhibits enormous variety in mechanism and many levels of complexity. Current researchers find regulatory events at every conceivable level of the processes that express genetic information. In the relatively simple
genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
of baker's yeast, (''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...
''), 405 of its 6,419 protein-encoding genes are directly involved in transcriptional control, compared to 1,938 that are enzymes.
Honours and awards
* 1962
Grand Prix Charles-Leopold Mayer by the
Académie des Sciences
* 1964 elected to the
American Academy of Arts and Sciences
The American Academy of Arts and Sciences (The Academy) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and other ...
* 1965
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
with
André Lwoff[ and Jacques Monod
* 1969 elected to the United States ]National Academy of Sciences
The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...
* 1969 elected to the American Philosophical Society
The American Philosophical Society (APS) is an American scholarly organization and learned society founded in 1743 in Philadelphia that promotes knowledge in the humanities and natural sciences through research, professional meetings, publicat ...
* 1973 Elected a Foreign Member of the Royal Society (ForMemRS)[
* 1996 Lewis Thomas Prize for Writing about Science
* 1996 ]Académie française
An academy (Attic Greek: Ἀκαδήμεια; Koine Greek Ἀκαδημία) is an institution of tertiary education. The name traces back to Plato's school of philosophy, founded approximately 386 BC at Akademia, a sanctuary of Athena, the go ...
Seat 38
See also
* List of Jewish Nobel laureates
References
Bibliography
* Jacob, François; E. L. Wollman. ''Sexuality and the Genetics of Bacteria''. Academic Press, 1961
* Jacob, François. ''The Possible & The Actual''. Pantheon Books, 1982
* Jacob, François. ''The Statue Within: An Autobiography'' by, translated from the 1987 French edition by Franklin Philip. Basic Books, 1988. ; new edition: 9780879694760
* Jacob, François. ''The Logic of Life''. translated from the 1976 French edition by Princeton University Press, 1993
* Jacob, François. ''Of Flies, Mice and Men'', translated from the French edition and published by Harvard University Press, 1998
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External links
*
François Jacob tells his life story at Web of Stories
(video)
{{DEFAULTSORT:Jacob, Francois
1920 births
2013 deaths
Academic staff of the Collège de France
French geneticists
French atheists
People of French-Jewish descent
French biochemists
Members of the Académie Française
French molecular biologists
Nobel laureates in Physiology or Medicine
French Nobel laureates
Jewish French scientists
Foreign members of the Royal Society
Foreign associates of the National Academy of Sciences
Members of the European Molecular Biology Organization
Phage workers
Members of the French Academy of Sciences
Scientists from Nancy, France
Lycée Carnot alumni
Pasteur Institute
Members of the American Philosophical Society
University of Paris alumni