François Jacob
Encyclopedia
François Jacob is a French
biologist
who, together with Jacques Monod
, originated the idea that control of enzyme
levels in all cell
s occurs through feedback
on transcription
. He shared the 1965 Nobel Prize in Medicine with Jacques Monod
and André Lwoff.
, 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.
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; 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. 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 tyrothricin
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 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.
expression
levels in cells is a result of feedback on the transcription
of DNA
sequences. Their experiment
s 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 bacteria
l and other cells could respond to external conditions by regulating levels of their key metabolic enzymes, and/or the activity of these enzyme
s. 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 molecule
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
, 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 gene
s 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 extended this repressor model to all genes in all organism
s 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.
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
biologist
Biologist
A biologist is a scientist devoted to and producing results in biology through the study of life. Typically biologists study organisms and their relationship to their environment. Biologists involved in basic research attempt to discover underlying mechanisms that govern how organisms work...
who, together with Jacques Monod
Jacques Monod
Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...
, originated the idea that control of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
levels in all cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s occurs through feedback
Feedback
Feedback describes the situation when output from an event or phenomenon in the past will influence an occurrence or occurrences of the same Feedback describes the situation when output from (or information about the result of) an event or phenomenon in the past will influence an occurrence or...
on transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. He shared the 1965 Nobel Prize in Medicine with Jacques Monod
Jacques Monod
Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...
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 CarnotLycée Carnot
The Lycée Carnot is a public secondary and higher education school located at 145 Boulevard Malesherbes in the 17th arrondissement, Paris, France. A prestigious Parisian high school, it is also known as one the best classe préparatoire aux écoles de commerce...
, 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
Secular Jewish culture
Secular Jewish culture embraces several related phenomena; above all, it is the international culture of secular communities of Jewish people, but it can also include the cultural contributions of individuals who identify as secular Jews...
; shortly after his bar mitzvah 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
École Polytechnique
The École Polytechnique is a state-run institution of higher education and research in Palaiseau, Essonne, France, near Paris. Polytechnique is renowned for its four year undergraduate/graduate Master's program...
. 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; 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. For his wartime service, he was awarded France's WWII highest decoration for valor, the Cross of Liberation
Ordre de la Libération
The Ordre de la Libération is a French Order awarded to heroes of the Liberation of France during World War II. It is an exceptional honor, the second highest after the Légion d’Honneur and only a small number of people and military units have received it, exclusively for deeds accomplished...
, as well as Légion d'honneur
Légion d'honneur
The Legion of Honour, or in full the National Order of the Legion of Honour is a French order established by Napoleon Bonaparte, First Consul of the Consulat which succeeded to the First Republic, on 19 May 1802...
and croix de guerre
Croix de guerre
The Croix de guerre is a military decoration of France. It was first created in 1915 and consists of a square-cross medal on two crossed swords, hanging from a ribbon with various degree pins. The decoration was awarded during World War I, again in World War II, and in other conflicts...
.
After his recovery, Jacob returned to medical school and began researching tyrothricin
Tyrothricin
Tyrothricin is a cyclic polypeptide-antibiotic mixture from Bacillus brevis. It is a locally effective antibiotic effective against gram-positive bacteria. It is sometimes combined with benzocaine 5 mg to provide relief from sore throats...
and learning the methods of bacteriology
Bacteriology
Bacteriology is the study of bacteria. This subdivision of microbiology involves the identification, classification, and characterization of bacterial species...
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 antibiotic, tyrothricin
Tyrothricin
Tyrothricin is a cyclic polypeptide-antibiotic mixture from Bacillus brevis. It is a locally effective antibiotic effective against gram-positive bacteria. It is sometimes combined with benzocaine 5 mg to provide relief from sore throats...
. 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.
Research
In 1961 Jacob and Monod explored the idea that the control of enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
levels in cells is a result of feedback on the transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
sequences. Their experiment
Experiment
An experiment is a methodical procedure carried out with the goal of verifying, falsifying, or establishing the validity of a hypothesis. Experiments vary greatly in their goal and scale, but always rely on repeatable procedure and logical analysis of the results...
s and ideas gave impetus to the emerging field of molecular developmental biology
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
, and of transcriptional regulation
Transcriptional regulation
Transcriptional regulation is the change in gene expression levels by altering transcription rates. -Regulation of transcription:Regulation of transcription controls when transcription occurs and how much RNA is created...
in particular.
For many years it had been known that bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l and other cells could respond to external conditions by regulating levels of their key metabolic enzymes, and/or the activity of these enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s. For instance, if a bacterium finds itself in a broth
Broth
Broth is a liquid food preparation, typically consisting of either water or an already flavored stock, in which bones, meat, fish, cereal grains, or vegetables have been simmered. Broth is used as a basis for other edible liquids such as soup, gravy, or sauce. It can be eaten alone or with garnish...
containing lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
, rather than the simpler sugar glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, it must adapt itself to the need to 1) import lactose, 2) cleave lactose to its constituents glucose and galactose
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
, 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
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
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
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, 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
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
, which in turn is decoded into protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
).
This repressor (the lac repressor
Lac repressor
The lac repressor is a DNA-binding protein which inhibits the expression of genes coding for proteins involved in the metabolism of lactose in bacteria. These genes are repressed when lactose is not available to the cell, ensuring that the bacterium only invests energy in the production of...
) is made in all cells, binding directly to DNA at the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s 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 extended this repressor model to all genes in all organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
s in their initial exuberance. The regulation of gene activity has developed into a very large sub-discipline of molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, 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
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
of baker's yeast, (saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
), 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 MayerGran Prix Charles-Leopold MayerThe Grand Prix Charles-Léopold Mayer is awarded annually by the Académie des Sciences de l'Institut de France to researchers who have performed outstanding work in the biological sciences; especially in the areas of cell or molecular biology...
by the Académie des Sciences in 1962. - François Jacob was awarded, together with André Lwoff and Jacques MonodJacques MonodJacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...
, the 1965 Nobel Prize in Physiology or MedicineNobel Prize in Physiology or MedicineThe Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
. - François Jacob received the Lewis Thomas Prize for Writing about ScienceLewis Thomas PrizeThe Lewis Thomas Prize for Writing about Science, named for its first recipient, Lewis Thomas, is an annual literary prize awarded by Rockefeller University to scientists deemed to have accomplished a significant literary achievement: it "recognizes scientists as poets"...
for 1996. - François Jacob was elected a member of the Académie françaiseAcadémie françaiseL'Académie française , also called the French Academy, is the pre-eminent French learned body on matters pertaining to the French language. The Académie was officially established in 1635 by Cardinal Richelieu, the chief minister to King Louis XIII. Suppressed in 1793 during the French Revolution,...
in 1996.
Books
- Sexuality and the Genetics of Bacteria by E. L. 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. ISBN 9780465082230; new edition: 9780879694760
- 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
See also
- History of RNA biologyHistory of RNA biologyNumerous key discoveries in biology have emerged from studies of RNA , including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that...
- List of Jewish Nobel laureates
- List of RNA biologists