François Jacob

Infobox Scientist |name =François Jacob
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birth_place =Nancy, France
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citizenship =French
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known_for =operon
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prizes = 1965 Nobel Prize in Medicine
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François Jacob (born 17 June 1920 in Nancy, France) is a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through feedback on transcription. He shared the 1965 Nobel Prize in Medicine with Jacques Monod and André Lwoff.

Childhood and education

François Jacob is the only child of Simon and Thérèse Jacob. An inquisitive child, he learned to read at a young age. 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 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 he became an atheist. [Jacob, "The Statue Within", pp 20-57. Quotes from pp 42 and 53.]

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. [Jacob, "The Statue Within", pp 84-88. Quote from p 86]

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; he did not return to France until 1 August 1944, after four years in service in North Africa. He was injured in a German air attack, and was sent to now-liberated Paris to recover. [Jacob, "The Statue Within", pp 98-165] For his wartime service, he was awarded France's WWII highest decoration for valor, the Cross of Liberation, as well as Légion d'honneur and croix de guerre.

After his recovery, Jacob returned to medical school and began researching penicillin, which had been developed for mass production during the war—and learning the methods of bacteriology 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 another antibiotic, tyrothricin. Later, the center was contracted to convert gunpowder factories for penicillin production (though this proved impossible). [Jacob, "The Statue Within", pp 166-199]

Also in this period, he met and began courting his future wife, Lise. [Jacob, "The Statue Within", pp 199-206]

Research

In 1961 Jacob and Monod explored the idea that the control of enzyme expression levels in cells is a result of feedback on the transcription of DNA sequences. Their experiments and ideas gave impetus to the emerging field of molecular developmental biology, 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 enzymes, and/or the activity of these enzymes. For instance, if a bacterium finds itself in a broth containing lactose, rather than the simpler sugar glucose, 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 molecules 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, 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, which in turn is decoded into protein).

This repressor (the lac repressor) is made in all cells, binding directly to DNA at the genes it controls, and physically preventing the transcription apparatus from gaining access to the DNA. In the presence of lactose, this repressor binds lactose, 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 somewhat recklessly extended this repressor model to all genes in all organisms in their initial exuberance. The regulation of gene activity has developed into a very large sub-discipline of molecular biology, 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 of baker's yeast, ("saccharomyces cerevisiae"), 405 of its 6,419 protein-encoding genes are directly involved in transcriptional control, compared to 1,938 that are enzymes.

Awards and recognition

*François Jacob was awarded the Gran Prix Charles-Leopold Mayer by the Académie des Sciences in 1962
*François Jacob was awarded, together with André Lwoff and Jacques Monod, the 1965 Nobel Prize in Physiology or Medicine.
* François Jacob received the Lewis Thomas Prize for Writing about Science for 1996.
*François Jacob was elected a member of the Académie française in 1996.

Books

*"Sexuality and the Genetics of Bacteria" by E.H. Wollmann and François Jacob, published by Academic Press, 1961
*"The Possible & The Actual" by François Jacob, published in the United States by Pantheon Books, and in Canada by Random House of Canada, 1982
*"The Statue Within: An Autobiography" by François Jacob, translated from the 1987 French edition by Franklin Philip. Basic Books, 1988.
*"The Logic of Life" by François Jacob, translated from the 1976 French edition by Princeton University Press 1993
*"Of Flies, Mice and Men" by François Jacob, translated from the French edition and published by Harvard University Press, 1998

Publications

*Citation
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url= http://www.ncbi.nlm.nih.gov/pubmed/15999435
last=Jacob
first=François
last2=Perrin
first2=David
last3=Sánchez
first3=Carmen
last4=Monod
first4=Jacques
publication-date=2005 Jun
year=2005
title= [The operon: a group of genes with expression coordinated by an operator. C.R.Acad. Sci. Paris 250 (1960) 1727-1729]
volume=328
issue=6
periodical=C. R. Biol.
pages=514-20
*Citation
id = PMID:4868117
url= http://www.ncbi.nlm.nih.gov/pubmed/4868117
last=Ullmann
first=A
last2=Jacob
first2=F
last3=Monod
first3=J
publication-date=1968 Feb 28
year=1968
title=On the subunit structure of wild-type versus complemented beta-galactosidase of Escherichia coli.
volume=32
issue=1
periodical=J. Mol. Biol.
pages=1-13
*Citation
id = PMID:5339877
url= http://www.ncbi.nlm.nih.gov/pubmed/5339877
last=Ullmann
first=A
last2=Jacob
first2=F
last3=Monod
first3=J
publication-date=1967 Mar 14
year=1967
title=Characterization by in vitro complementation of a peptide corresponding to an operator-proximal segment of the beta-galactosidase structural gene of Escherichia coli.
volume=24
issue=2
periodical=J. Mol. Biol.
pages=339-43
*Citation
id = PMID:4285628
url= http://www.ncbi.nlm.nih.gov/pubmed/4285628
last=Ullmann
first=A
last2=Perrin
first2=D
last3=Jacob
first3=F
last4=Monod
first4=J
publication-date=1965 Jul
year=1965
title= [Identification, by in vitro complementation and purification, of a peptide fraction of Escherichia coli beta-galactosidase]
volume=12
issue=3
periodical=J. Mol. Biol.
pages=918-23
*Citation
id = PMID:14153528
url= http://www.ncbi.nlm.nih.gov/pubmed/14153528
last=WILLSON
first=C
last2=PERRIN
first2=D
last3=COHN
first3=M
last4=JACOB
first4=F
publication-date=1964 Apr
year=1964
title=NON-INDUCIBLE MUTANTS OF THE REGULATOR GENE IN THE "LACTOSE" SYSTEM OF ESCHERICHIA COLI.
volume=8
issue=
periodical=J. Mol. Biol.
pages=582-92
*Citation
id = PMID:14143651
url= http://www.ncbi.nlm.nih.gov/pubmed/14143651
last=JACOB
first=F
last2=ULLMAN
first2=A
last3=MONOD
first3=J
publication-date=1964 Mar 16
year=1964
title= [THE PROMOTOR, A GENETIC ELEMENT NECESSARY TO THE EXPRESSION OF AN OPERON.]
volume=258
issue=
periodical=C. R. Hebd. Seances Acad. Sci.
pages=3125-8
*Citation
id = PMID:14270538
url= http://www.ncbi.nlm.nih.gov/pubmed/14270538
last=JACOB
first=F
last2=MONOD
first2=J
publication-date=1964
year=1964
title= [BIOCHEMICAL AND GENETIC MECHANISMS OF REGULATION IN THE BACTERIAL CELL.]
volume=46
issue=
periodical=Bull. Soc. Chim. Biol.
pages=1499-532
*Citation
id = PMID:13936070
url= http://www.ncbi.nlm.nih.gov/pubmed/13936070
last=MONOD
first=J
last2=CHANGEUX
first2=J P
last3=JACOB
first3=F
publication-date=1963 Apr
year=1963
title=Allosteric proteins and cellular control systems.
volume=6
issue=
periodical=J. Mol. Biol.
pages=306-29
*Citation
id = PMID:14036499
url= http://www.ncbi.nlm.nih.gov/pubmed/14036499
last=JACOB
first=F
last2=SUSSMAN
first2=R
last3=MONOD
first3=J
publication-date=1962 Jun 13
year=1962
title= [On the nature of the repressor ensuring the immunity of lysogenic bacteria.]
volume=254
issue=
periodical=C. R. Hebd. Seances Acad. Sci.
pages=4214-6
*Citation
id = PMID:13718526
url= http://www.ncbi.nlm.nih.gov/pubmed/13718526
last=JACOB
first=F
last2=MONOD
first2=J
publication-date=1961 Jun
year=1961
title=Genetic regulatory mechanisms in the synthesis of proteins.
volume=3
issue=
periodical=J. Mol. Biol.
pages=318-56
*Citation
id = PMID:14475415
url= http://www.ncbi.nlm.nih.gov/pubmed/14475415
last=MONOD
first=J
last2=JACOB
first2=F
publication-date=1961
year=1961
title=Teleonomic mechanisms in cellular metabolism, growth, and differentiation.
volume=26
issue=
periodical=Cold Spring Harb. Symp. Quant. Biol.
pages=389-401
*Citation
id = PMID:13734531
url= http://www.ncbi.nlm.nih.gov/pubmed/13734531
last=PERRIN
first=D
last2=JACOB
first2=F
last3=MONOD
first3=J
publication-date=1960 Jul 4
year=1960
title= [Induced biosynthesis of a genetically modified protein not presenting affinity for the inductor.]
volume=251
issue=
periodical=C. R. Hebd. Seances Acad. Sci.
pages=155-7
*Citation
id = PMID:13806544
url= http://www.ncbi.nlm.nih.gov/pubmed/13806544
last=BUTTIN
first=G
last2=JACOB
first2=F
last3=MONOD
first3=J
publication-date=1960 Mar 28
year=1960
title= [Constituent synthesis of galactokinase following the development of lambda bacteriophages in Escherichia coli K 12.]
volume=250
issue=
periodical=C. R. Hebd. Seances Acad. Sci.
pages=2471-3
*Citation
id = PMID:14406329
url= http://www.ncbi.nlm.nih.gov/pubmed/14406329
last=JACOB
first=F
last2=PERRIN
first2=D
last3=SANCHEZ
first3=C
last4=MONOD
first4=J
publication-date=1960 Feb 29
year=1960
title= [Operon: a group of genes with the expression coordinated by an operator.]
volume=250
issue=
periodical=C. R. Hebd. Seances Acad. Sci.
pages=1727-9
*Citation
id = PMID:14406327
url= http://www.ncbi.nlm.nih.gov/pubmed/14406327
last=JACOB
first=F
last2=MONOD
first2=J
publication-date=1959 Oct 5
year=1959
title= [Genes of structure and genes of regulation in the biosynthesis of proteins.]
volume=249
issue=
periodical=C. R. Hebd. Seances Acad. Sci.
pages=1282-4
*Citation
id = PMID:13547552
url= http://www.ncbi.nlm.nih.gov/pubmed/13547552
last=PARDEE
first=A B
last2=JACOB
first2=F
last3=MONOD
first3=J
publication-date=1958 May 28
year=1958
title= [The role of the inducible alleles and the constrtutive alleles in the synthesis of beta-galactosidase in zygotes of Escherichia coli.]
volume=246
issue=21
periodical=C. R. Hebd. Seances Acad. Sci.
pages=3125-8
*Citation
id = PMID:14905606
url= http://www.ncbi.nlm.nih.gov/pubmed/14905606
last=JACOB
first=F
last2=TORRIANI
first2=A M
last3=MONOD
first3=J
publication-date=1951 Nov 12
year=1951
title= [Effect of ultraviolet rays on the biosynthesis of galactosidase and on the multiplication of T2 bacteriophage in Escherichia coli.]
volume=233
issue=20
periodical=C. R. Hebd. Seances Acad. Sci.
pages=1230-2

Footnotes

External links

* [http://nobelprize.org/medicine/laureates/1965/jacob-bio.html Nobel biography]
*
* [http://www.academie-francaise.fr/immortels/index.html L'Académie française]
* [http://okilpob.tripod.com/mkdir/jacob-speech.html Discoveries concerning genetic control of enzyme and virus synthesis. ]