Jacques Monod

Jacques Lucien Monod (February 9, 1910 – May 31, 1976), a French biochemist, won the 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".[2][3][4][5][6][7]

Monod (along with François Jacob) became famous for his work on the E. coli lac operon, which encodes proteins necessary for the transport and breakdown of the sugar lactose (lac). From their own work and the work of others, he and Jacob came up with a model for how the levels of some proteins in a cell are controlled. In their model, the manufacture of proteins, such as the ones encoded within the lac (lactose) operon, is prevented when a repressor, encoded by a regulatory gene, binds to its operator, a specific site on the DNA next to the genes encoding the proteins. (It is now known that repressor bound to the operator physically blocks RNA polymerase from binding to the promoter, the site where transcription of the adjacent genes begins.)

Study of the control of expression of genes in the lac operon provided the first example of a transcriptional regulation system. Monod also suggested the existence of mRNA molecules that link the information encoded in DNA and proteins. He is widely regarded as one of the founders of molecular biology.[8][9] Monod's interest in the lac operon originated from his doctoral dissertation, for which he studied the growth of bacteria in culture media containing two sugars.[10][11][12][13]

Jacques Monod

Jacques Monod nobel
Born
Jacques Lucien Monod

February 9, 1910
Paris, France
DiedMay 31, 1976 (aged 66)
Cannes, France
NationalityFrench
Known for
Awards
Scientific career
Fields

Career and research

In Monod's studies he discovered that the course work was decades behind the current biological science. He learned from other students a little older than himself, rather than from the faculty. "To George Teissier he owes a preference for quantitative descriptions; André Lwoff initiated him into the potentials of microbiology; to Boris Ephrussi he owes the discovery of physiological genetics, and to Louis Rapkine the concept that only chemical and molecular descriptions could provide a complete interpretation of the function of living organisms."[14]

Before his doctoral work, Monod spent a year in the laboratory of Thomas Hunt Morgan at the California Institute of Technology working on Drosophila genetics. This was a true revelation for him and probably influenced him on developing a genetic conception of biochemistry and metabolism.[15]

His doctoral work explored the growth of bacteria on mixtures of sugars and documented the sequential utilization of two or more sugars. He coined the term diauxie to denote the frequent observations of two distinct growth phases of bacteria grown on two sugars. He theorized on the growth of bacterial cultures and promoted the chemostat theory as a powerful continuous culture system to investigate bacterial physiology.[16]

The experimental system ultimately used by Jacob and Monod was a common bacterium, E. coli, but the basic regulatory concept (described in the Lac operon article) that was discovered by Jacob and Monod is fundamental to cellular regulation for all organisms. The key idea is that E. coli does not bother to waste energy making such enzymes if there is no need to metabolize lactose, such as when other sugars like glucose are available. The type of regulation is called negative gene regulation, as the operon is inactivated by a protein complex that is removed in the presence of lactose (regulatory induction).

Monod also made important contributions to the field of enzymology with his proposed theory of allostery in 1965 with Jeffries Wyman (1901-1995) and Jean-Pierre Changeux.[17]

Monod was not only a biologist but also a fine musician and esteemed writer on the philosophy of science. He was a political activist and chief of staff of operations for the Forces Françaises de l'Interieur during World War II. In preparation for the Allied landings, he arranged parachute drops of weapons, railroad bombings, and mail interceptions.

Philosophical contributions

Monod published Chance and Necessity in 1971 (based on a series of lectures given at Pomona College in 1969), a short but influential examination of the philosophical implications of modern biology, appropriate for a nontechnical audience.[18] He acknowledges his connection to the French existentialists in the epigraph of the work, which quotes the final paragraphs of Camus' The Myth of Sisyphus. In summarizing recent progress in several areas of biology (including his own research), he highlights the ways in which information was found to take physical form and hence be capable of influencing events in the world. For example, the information allowing a protein enzyme to 'select' only one of several similar compounds as the substrate of a chemical reaction is encoded in the precise 3-dimensional shape of the enzyme; that precise shape is itself encoded by the linear sequence of amino acids comprising the protein; that particular sequence of amino acids is encoded by the sequence of nucleotides in the gene for that enzyme.

'Necessity,' in the title of his work, refers to the fact that the enzyme must act as it does, catalyzing a reaction with one substrate but not another, according to the constraints imposed by its structure. While the enzyme itself cannot be said in any meaningful way to have a choice about its activity, the thrust of Jacob and Monod's Nobel prize-winning research was to show how a bacterial cell can choose whether or not to carry out the reaction catalyzed by the enzyme. As he explains, one way the cell can make such a choice is by either synthesizing the enzyme or not, in response to its chemical environment. However, the synthesis/no synthesis choice is in turn governed by necessary biochemical interactions between a repressor protein, the gene for the enzyme, and the substrate of the enzyme, which interact such that the outcome (enzyme synthesis or not) differs according to the variable composition of the cell's chemical environment. The hierarchical, modular organization of this system clearly implies that additional regulatory elements can exist that govern, are governed by, or otherwise interact with any given set of regulatory components. Because in general, the bacterial activity that results from these regulatory circuits is in accord with what is beneficial for the bacterial cell's survival at that time, the bacterium as a whole can be described as making rational choices, even though the bacterial components involved in deciding whether to make an enzyme (repressor, gene, and substrate) have no more choice about their activities than does the enzyme itself.

Monod shows us a paradigm of how choice at one level of biological organization (metabolic activity) is generated by necessary (choiceless) interactions at another level (gene regulation); the ability to choose arises from a complex system of feedback loops that connect these interactions. He goes on to explain how the capacity of biological systems to retain information, combined with chance variations during the replication of information (i.e. genetic mutations) that are individually rare but commonplace in aggregate, leads to the differential preservation of that information which is most successful at maintaining and replicating itself. Monod writes that this process, acting over long periods of time, is a sufficient explanation (indeed the only plausible explanation) for the complexity and teleonomic activity of the biosphere. Hence, the combined effects of chance and necessity, which are amenable to scientific investigation, account for our existence and the universe we inhabit, without the need to invoke mystical, supernatural, or religious explanations.

While acknowledging the likely evolutionary origin of a human need for explanatory myths, in the final chapter of Chance and Necessity, Monod advocates for adopting an objective (hence value-free), scientific worldview as our guide to assessing truth. He describes this as an 'ethics of knowledge', which disrupts the older philosophical, mythological and religious ontologies that claimed to provide both ethical values and a standard for judging truth. For Monod, assessing truth separate from any value judgment is what frees humans to act authentically, by requiring that they choose the ethical values that motivate their actions. He concludes "...man at last knows he is alone in the unfeeling immensity of the universe, out of which he has emerged only by chance. His destiny is nowhere spelled out, nor is his duty. The kingdom above or the darkness below; it is for him to choose".[19] While apparently bleak, in comparison to the concepts that humanity belongs to some inevitable, universal process, or that a benevolent God created and protects us, an acceptance of the scientific assessment described in the first part of the quote is, for Monod, the only possible basis of an authentic, ethical human life. It is reasonable to conclude that Monod himself did not find this position bleak; the quote he chose from Camus to introduce Chance and Necessity ends with the famous sentence "One must imagine Sisyphus happy."

His views were in direct opposition to the religious certainties of his ancestor Henri's[20] brothers, Frédéric Monod and Adolphe Monod, who were prominent evangelical preachers in the 19th century. In 1973, Jacques Monod was one of the signers of the Humanist Manifesto II.[21]

Sociologist Howard L. Kaye has suggested that Monod failed in his attempt to banish "mind and purpose from the phenomenon of life" in the name of science.[22] It may be more accurate to suggest that Monod sought to include mind and purpose within the purview of scientific investigation, rather than attributing them to supernatural or divine causes. While not explicitly addressing mind or consciousness, his scientific research demonstrated that biology includes feedback loops that govern interacting systems of biochemical reactions, such that the system as a whole can be described as having a purpose and making choices. Monod's philosophical writing indicates that he recognized the implication that such systems could arise and be elaborated upon by evolution through natural selection. The importance of Monod's work as a bridge between the chance and necessity of evolution and biochemistry on the one hand, and the human realm of choice and ethics on the other, can be judged by his influence on philosophers, biologists and computer scientists such as Daniel Dennett, Douglas Hofstadter, Marvin Minsky and Richard Dawkins.

Awards and honours

In addition to winning the Nobel Prize, Monod was also the Légion d'honneur and elected a Foreign Member of the Royal Society (ForMemRS) in 1968[1]

Personal life

Monod was born in Paris to an American mother from Milwaukee, Charlotte (Sharlie) MacGregor Todd, and a French Huguenot father, Lucien Monod who was a painter and inspired him artistically and intellectually.[1][14] He attended the lycée at Cannes until he was 18.[1] In October 1928 he started his studies in biology at the Sorbonne.[1] During World War II, Monod was active in the French Resistance, eventually becoming the chief of staff of the French Forces of the Interior.[23] He was an Chevalier in the Légion d'Honneur (1945), and was awarded the Croix de Guerre (1945) and the American Bronze Star Medal.[24][25]

In 1938 he married Odette Bruhl (d.1972).[26]

Jacques Monod died of leukemia in 1976 and was buried in the Cimetière du Grand Jas in Cannes on the French Riviera.

Quotations

  • "The first scientific postulate is the objectivity of nature: nature does not have any intention or goal."[4]
  • "Anything found to be true of E. coli must also be true of elephants."[27]
  • "The universe is not pregnant with life nor the biosphere with man...Man at last knows that he is alone in the unfeeling immensity of the universe, out of which he emerged only by chance. His destiny is nowhere spelled out, nor is his duty. The kingdom above or the darkness below; it is for him to choose"[28]

References

  1. ^ a b c d e Lwoff, A. M. (1977). "Jacques Lucien Monod. 9 February 1910 -- 31 May 1976". Biographical Memoirs of Fellows of the Royal Society. 23: 384–412. doi:10.1098/rsbm.1977.0015.
  2. ^ "The Nobel Prize in Physiology or Medicine 1965 François Jacob, André Lwoff, Jacques Monod". Nobelprize.org. Retrieved June 30, 2010.
  3. ^ The Statue Within: an autobiography by François Jacob, Basic Books, 1988. ISBN 0-465-08223-8 Translated from the French. 1995 paperback: ISBN 0-87969-476-9
  4. ^ a b Chance and Necessity: An Essay on the Natural Philosophy of Modern Biology by Jacques Monod, New York, Alfred A. Knopf, 1971, ISBN 0-394-46615-2
  5. ^ Of Microbes and Life, Jacques Monod, Ernest Bornek, June 1971, Columbia University Press, ISBN 0-231-03431-8
  6. ^ The Eighth Day of Creation: makers of the revolution in biology by Horace Freeland Judson, Simon and Schuster, 1979. ISBN 0-671-22540-5. Expanded Edition Cold Spring Harbour Laboratory Press, 1996. ISBN 0-87969-478-5. Widely-praised history of molecular biology recounted through the lives and work of the major figures, including Monod.
  7. ^ Origins of Molecular Biology: a Tribute to Jacques Monod edited by Agnes Ullmann, Washington, ASM Press, 2003, ISBN 1-55581-281-3. Jacques Monod seen by persons who interacted with him as a scientist.
  8. ^ Ullmann, Agnès (2003). Origins of molecular biology: a tribute to Jacques Monod. ASM Press. p. xiv. ISBN 1-55581-281-3.
  9. ^ Stanier, R. (1977). "Jacques Monod, 1910–1976". Journal of General Microbiology. 101 (1): 1–12. doi:10.1099/00221287-101-1-1. PMID 330816.
  10. ^ From enzymatic adaptation to allosteric transitions, Jacques Monod, Nobel Lecture, December 11, 1965
  11. ^ Biography of Jacques Monod at Nobel e-Museum
  12. ^ Video interview with Jacques Monod Vega Science Trust
  13. ^ From enzymatic adaptation to allosteric transitions Nobel Lecture, December 11, 1965
  14. ^ a b "Jacques Monod – Biography". Nobelprize.org. Retrieved June 30, 2010.
  15. ^ Peluffo, Alexandre E. (July 1, 2015). "The "Genetic Program": Behind the Genesis of an Influential Metaphor". Genetics. 200 (3): 685–696. doi:10.1534/genetics.115.178418. ISSN 0016-6731. PMC 4512536. PMID 26170444.
  16. ^ 1949, Annu. Rev. Microbiol., 3:371–394; 1950, Ann. Inst. Pasteur., 79:390–410
  17. ^ Monod, J.; Wyman, J.; Changeux, J. P. (1965). "On the Nature of Allosteric Transitions: A Plausible Model". Journal of Molecular Biology. 12: 88–118. doi:10.1016/S0022-2836(65)80285-6. PMID 14343300.
  18. ^ Monad, Jacques (1971). Chance and Necessity. p. xii.
  19. ^ Monod, Jacques (1971). Chance and Necessity. New York: Alfred A. Knopf. p. 180. ISBN 0-394-46615-2.
  20. ^ fr:Descendance de Jean Monod (1765-1836)
  21. ^ "Humanist Manifesto II". American Humanist Association. Archived from the original on October 20, 2012. Retrieved October 10, 2012.
  22. ^ Kaye, Howard L. The Social Meaning of Modern Biology (1997) Transaction Publishers p. 75
  23. ^ Caroll, Sean (2013). Brave Genius: A Scientist, a Philosopher, and Their Daring Adventures from the French Resistance to the Nobel Prize. Crown Publishing Group. ISBN 978-0307952332.
  24. ^ Prial, Frank (June 1, 1976). "Jacques Monod, Nobel Biologist, Dies; Thought Existence Is Based on Chance". The New York Times. Retrieved October 11, 2013.
  25. ^ "Jacques Monod – Biographical". www.nobelprize.org. Retrieved December 20, 2016.
  26. ^ Biographical Index of Former Fellows of the Royal Society of Edinburgh 1783–2002 (PDF). The Royal Society of Edinburgh. July 2006. ISBN 0 902 198 84 X.
  27. ^ Friedmann, Herbert Claus (2004). "From 'Butyribacterium' to 'E. coli' : An Essay on Unity". Biochemistry Perspectives in Biology and Medicine. 47 (1): 47–66. doi:10.1353/pbm.2004.0007.
  28. ^ Davies, Paul (2010). The Eerie Silence. Boston, New York: Houghton Mifflin Harcourt. p. 25. ISBN 978-0-547-13324-9.

Further reading

  • Sean B. Carroll (2014). Brave Genius: A Scientist, a Philosopher, and Their Daring Adventures from the French Resistance to the Nobel Prize. Broadway Books. ISBN 978-0307952349.
1910 in France

Events from the year 1910 in France.

Agnes Ullmann

Agnes Ullmann (April 14, 1927 – February 25, 2019) was a French microbiologist.

Boris Magasanik

Boris Magasanik (December 19, 1919 – December 25, 2013) was a microbiologist and biochemist who was the Jacques Monod Professor Emeritus of Microbiology in the Department of Biology at the Massachusetts Institute of Technology. After moving from Harvard Medical School in 1960, Magasanik spent the rest of his research career at MIT, including an influential decade as the head of the Department of Biology from 1967–77. Magasanik's research interests focused on gene regulation, including study of nitrogen metabolic regulation in bacteria, catabolite repression, and intracellular signaling via two-component systems. Magasanik retired in 1990 and died in 2013.

Clamart

Clamart (French pronunciation: ​[kla.maʁ]) is a commune in the southwestern suburbs of Paris, France. It is located 8.7 km (5.4 mi) from the center of Paris.

The town is divided into two parts, separated by a forest: bas Clamart, the historical centre, and petit Clamart with urbanization developed in the 1960s replacing pea fields. The canton of Clamart includes only a part of the commune. The other part of the commune belongs to the canton of Le Plessis-Robinson.

Diauxie

Diauxie is a Greek word coined by Jacques Monod to mean two growth phases. The word is used in English in cell biology to describe the growth phases of a microorganism in batch culture as it metabolizes a mixture of two sugars. Rather than metabolizing the two available sugars simultaneously, microbial cells commonly consume them in a sequential pattern, resulting in two separate growth phases.

François Jacob

François Jacob (17 June 1920 – 19 April 2013) was a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through regulation of transcription. He shared the 1965 Nobel Prize in Medicine with Jacques Monod and André Lwoff.

Gabriel Monod

Gabriel Monod (7 March 1844 – 10 April 1912) was a French historian, the nephew of Adolphe Monod.

Genetic program

In biology, a genetic program of a cell is a physiological change brought about by a temporal pattern of activation of a particular subset of genes.The metaphor was introduced simultaneously by Ernst Mayr and François Jacob, Jacques Monod in 1961 in two separate articles.

IJM

IJM may refer to:

IJM Corporation Berhad, a company in Malaysia

ImageJ Macro language, a programming language

International Justice Mission, a non-profit human rights organization

Institut Jacques Monod, a research institute in Paris, France

Institut Jacques Monod

The Institut Jacques Monod, funded jointly by the CNRS and the University Paris Diderot, is one of the main centres for basic research in biology in Paris, France. It is headed by Giuseppe Baldacci, professor at the University of Paris Diderot.

There are 3 broad research topics (Genome and chromosome dynamics, Cellular dynamics and signalling, Development and evolution) and 2 main transverse axes (Quantitative biology and modelling, Molecular and cellular pathologies). Research at the interface of biology with physics, mathematics, chemistry and medicine is strongly encouraged.

Some 300 people work at the Institute (tenured investigators, Ph.D. students, post-docs, technicians, engineers, French and foreign visitors, and administrative staff).

Jacques Monod (actor)

Jacques Monod (21 August 1918 – 25 December 1985) was a French actor. He appeared in more than one hundred films from 1947 to 1985.

Jacques Monod (disambiguation)

Jacques Monod may refer to:

Jacques Monod, French biochemist and Nobel Prize laureate

Jacques Monod (actor), French actor

Jacques-Louis Monod, American composer

Journal of Theoretical Biology

The Journal of Theoretical Biology is a biweekly peer-reviewed scientific journal covering theoretical biology, as well as mathematical, computational and statistical aspects of biology. Some research areas covered by the journal include cell biology, evolutionary biology, population genetics, morphogenesis, and immunology. It is often referred to informally by the initials 'JTB'.

The journal was established in 1961. Its founding editor-in-chief was English biologist James F. Danielli, who remained editor until his death in 1984. Other notable founding members of the Editorial Board included Melvin Calvin, Barry Commoner, Christian De Duve, Daniel Mazia, Jacques Monod, Conrad Waddington, and John Zachary Young. The Journal of Theoretical Biology is published by Elsevier and, as of 2014, the editors-in-chief are Denise Kirschner (University of Michigan Medical School), Yoh Iwasa (Kyushu University), and Lewis Wolpert (University College London). According to the Journal Citation Reports, the journal has a 2015 impact factor of 2.049.

List of Légion d'honneur recipients by name (M)

The following is a list of some notable Légion d'honneur recipients by name. The Légion d'honneur is the highest order of France. A complete, chronological list of the members of the Legion of Honour nominated from the very first ceremony in 1803 to now does not exist. The number is estimated at one million including about 3,000 Grand Cross.

Lycée Jacques-Monod

The lycée Jacques-Monod is a French institute of secondary and higher education located in Lescar (Pyrénées-Atlantiques). It has more than 800 students, and is located in a building with a rich history.

Messenger RNA

Messenger RNA (mRNA) is a large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression. RNA polymerase transcribes primary transcript mRNA (known as pre-mRNA) into processed, mature mRNA. This mature mRNA is then translated into a polymer of amino acids: a protein, as summarized in the central dogma of molecular biology.

As in DNA, mRNA genetic information is in the sequence of nucleotides, which are arranged into codons consisting of three base pairs each. Each codon encodes for a specific amino acid, except the stop codons, which terminate protein synthesis. This process of translation of codons into amino acids requires two other types of RNA: Transfer RNA (tRNA), that mediates recognition of the codon and provides the corresponding amino acid, and ribosomal RNA (rRNA), that is the central component of the ribosome's protein-manufacturing machinery.

The existence of mRNA was first suggested by Jacques Monod and François Jacob, and subsequently discovered by Jacob, Sydney Brenner and Matthew Meselson at the California Institute of Technology in 1961.

It should not be confused with mitochondrial DNA.

Michel E. Goldberg

Michel E. Goldberg is a French biophysicist who specialized in the study of protein folding and aggregation. He spent most of his scientific career at the Pasteur Institute, becoming a laboratory head in 1972 and serving as the Scientific Director from 1976 to 1979. He also held a variety of roles with the Pasteur-Weizmann Council, a partnership between the Pasteur Institute in France and the Weizmann Institute in Israel. Goldberg retired in 2005.

Monod equation

The Monod equation is a mathematical model for the growth of microorganisms. It is named for Jacques Monod who proposed using an equation of this form to relate microbial growth rates in an aqueous environment to the concentration of a limiting nutrient. The Monod equation has the same form as the Michaelis–Menten equation, but differs in that it is empirical while the latter is based on theoretical considerations.

The Monod equation is commonly used in environmental engineering. For example, it is used in the activated sludge model for sewage treatment.

Regulation of gene expression

Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. Although as early as 1951, Barbara McClintock showed interaction between two genetic loci, Activator (Ac) and Dissociator (Ds), in the color formation of maize seeds, the first discovery of a gene regulation system is widely considered to be the identification in 1961 of the lac operon, discovered by François Jacob and Jacques Monod, in which some enzymes involved in lactose metabolism are expressed by E. coli only in the presence of lactose and absence of glucose.

In multicellular organisms, gene regulation drives cellular differentiation and morphogenesis in the embryo, leading to the creation of different cell types that possess different gene expression profiles from the same genome sequence. Although this does not explain how gene regulation originated, evolutionary biologists include it as a partial explanation of how evolution works at a molecular level, and it is central to the science of evolutionary developmental biology ("evo-devo").

The initiating event leading to a change in gene expression includes activation or deactivation of receptors.

1901–1925
1926–1950
1951–1975
1976–2000
2001–present
Key concepts
Genetic architecture
Non-genetic influences
Developmental architecture
Evolution of genetic systems
Control of development
Influential figures
Debates

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