Sunday, March 11, 2012

Jacques Monod and the origins of molecular biology

A beautiful model or theory may not be right; but an ugly one must be wrong. 
Jacques Monod 

 Published by ASM Press
After his work on bacterial growth, I'm now reading about Monod's later career and the discoveries that contributed to the creation of molecular biology. And for that purpose, I warmly recommend the revised edition of "Origins of molecular biology – A tribute to Jacques Monod", published at ASM Press. In this book, Agnes Ullmann and André Lwoff (two former collaborators of Monod) have compiled a collection of essays by colleagues and peers who recall their memories of the great scientist (among whom François Jacob, Francis Crick, Salvador Luria and many others). The book should be praised for providing a mosaic view that tells both the story of the science and the story of the man. And what a man! Bacterial growth kinetics, messenger RNA, enzymatic repression, lac operon, allosteric proteins… A Nobel prize received in 1965 (together with André Lwoff and François Jacob) rewarded their «discoveries concerning the genetic regulation of enzyme and virus synthesis». But, although the book portrays Jacques Monod as an extraordinary man and a great scientist, this is no hagiography, and the darker sides of his personality are evoked as well. 

Let me quickly sketch his biography. Trained as a zoologist, Monod first studied protists in France, before being introduced to genetics in the mid 1930's during a stay at Caltech in the laboratory of Thomas Hunt Morgan. He returned one year later to Paris and started working on microbial growth. At that time, André Lwoff gave him an advice that would have huge consequences on his career: switching from protists to bacteria! His Ph.D. thesis, obtained in 1941, dealt with the growth of bacterial cultures – but this was World War II, Paris was occupied, and Jacques Monod had joined the Underground, which put him in trouble with the Gestapo and obliged him to become clandestine. After the war, he joined Lwoff's department at the Institut Pasteur where he resumed working on E. coli and enzymatic regulation. This led to many years of incredibly fruitful research, culminating in a 1961 review paper describing the lactose operon and postulating the existence of messenger RNA (Jacob and Monod, 1961). Later, Monod developed the concept of allosteric enzymes, before turning to more administrative duties when he was appointed director of the Institut Pasteur in 1971. He prematurely died in 1976, aged 66. [For a more detailed account of Monod's life, I recommend "Origins" or Ullmann, 2011.]

Now several thoughts about Ullmann's book, in no particular order:

Due to the diversity of the book contributors, all essays are not equally interesting, and I skipped a couple. Perhaps unsurprisingly, François Jacob provided one of the best accounts (he was a close collaborator of Monod and he is a wonderful writer himself). Jacob points at the somewhat dual personality of Monod: on the one hand a charming, generous man, and a great intellectual; on the other hand a dogmatic, arrogant person making black and white judgments. This dual portray is very present throughout the book, but even one of the most critical contributor, Martin Pollock, noted that:
 "I feel immensely privileged to have known Jacques Monod […]. It could, at times, be painful, frequently personally disappointing, and occasionally it was quite exasperating. But I would not have missed it for anything." 
The own account of Agnes Ullmann (the editor) is quite moving, since Jacques Monod helped her flee Hungary and move to the west in 1960. Some essays focus more on the science, some more on the man. Overall, the intertwined personal lives and scientific discoveries strongly remind us that science, well, is done by human beings…

One remarkable aspect of the book is the image it gives of scientific research at that time: vivid, exciting, fast-paced… The Institut Pasteur appears as a rallying point for countless talented scientists, among them many Americans. They helped define a discipline molecular biologywith which most biologists are still dealing today. To write in a kuhnian way, the paradigm of molecular biology is still alive and kicking. Most recent scientific advances were technical, not conceptual, and even systems biology appears as a continuation of the work of Jacob and Monod (Morange, 2010). 

Monod is arguably one of the greatest scientific figures of the twentieth century. In addition to his scientific work itself, which is considerable, he also wrote a book ("Chance and Necessity") that had great importance in the history of ideas. Yet, one might wonder whether his legacy is known to present biology students. As Michel Morange put it (Morange, 2010):
 "Ask French students who Monod was, and no one has an answer. A few may know what the operon model was, but they are unaware that Jacques Monod and Francois Jacob conceived it." 
And I would add: ask any student. It's not better this side of the Atlantic. I believe we really have to include much more history of science in the curriculum of biology students. But isn't it surprising that France has become so oblivious of Monod? I don't have the answer, but it saddens me that, as far as I know, the remarkable book by Agnes Ullmann is not available in a French translation…

Origins of molecular biology – A tribute to Jacques Monod. Edited by Agnes Ullmann (Revised edition, 2003). ASM Press.
Ullman, A. (2011). In memoriam: Jacques Monod (1910-1976). Genome Biol Evol 3, pp.1025-1033.
Morange, M. (2010). The scientific legacy of Jacques Monod. Research in Microbiology 161, pp.77-81.
Jacob F. and J. Monod (1961). Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology 3, pp. 218-256.

1 comment:

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