The diagram, a version of which appeared in their landmark paper, depicts how the operon is regulated in the absence or in the presence of an inducer, such as the sugar lactose. The key to the logic of this genetic on/off switch is the interaction of the inducer with the repressor. When no inducer is present, the repressor binds to the operator and keeps the genes of the operon turned off. When the inducer is present, it inhibits binding of the repressor to the operator, and the genes of the operon are switched on. In this way, for example, certain enzymes are made only when a certain nutrient is available.
SUBSEQUENT DISCOVERIES
The repressor protein, a critical component of the lactose regulatory system, was not isolated until 1966. Walter Gilbert and Benno Müller-Hill of Harvard University achieved that coup, and demonstrated that the repressor bound specifically to the operator sequence of the lactose operon. Moreover, the binding of the repressor to DNA was inhibited by inducers. The latter was an example of allostery, in which the binding of a molecule alters the shape and activity of a protein.
Allostery was yet another powerful idea conceived and coined by Monod. When he realized that the activities of some proteins, such as repressors, might be regulated by the binding of substances, he declared, “I have discovered the second secret of life!” Indeed, allostery underlies much biological regulation, such as how hormones regulate physiology.
The repressor for bacteriophage lambda was also isolated in 1966, by Mark Ptashne—also at Harvard. Ptashne demonstrated that lambda repressor bound specifically to the operator region of the bacteriophage DNA. The similarities between the two systems of regulation were in fact as great as Jacob had imagined years earlier.
The elucidation of the lactose and lambda phage regulatory systems provided critical tools for the early days of molecular genetics, in both basic and applied research. Many of the first practical advances in genetic engineering relied on knowledge developed from study of these two systems.
The general principle revealed by study of the lactose operon and bacteriophage was that genes were switched on and off by the action of proteins that bound specifically to DNA sequences near genes (operators). While the details are a bit different in more complex organisms, the principle is the same from E. coli to elephants to humans. As Monod anticipated in 1947, and as Jacob and Monod explicitly argued in their masterful synthesis published in 1961, the development of complex creatures and the differentiation of the many kinds of cell types in animal bodies are orchestrated by the turning on and off of different sets of genes. Most of that action is controlled through the binding of regulatory proteins to specific DNA sequences around genes.
ACKNOWLEDGMENTS
HOW DOES A middle-aged American biologist wind up writing a story about world-turning events and remarkable people in France more than seventy years ago?
That is a bit of a long story, although I promise not nearly as long as the book!
In explaining how he selected topics for books, the great biographer David McCullough admitted, “I sometimes get the feeling that the subject picks me.” I recognize that feeling here. My preparation for the book was a matter of chance. Writing it eventually became one of necessity.
The seeds were planted a very long time ago. In 1977, Simon Silver, my freshman adviser at Washington University in St. Louis, slid a book on the operon in front of me. I understood later that he was testing me, to see whether I was curious enough to do some extracurricular reading. I was. Simon later offered Zhores Medvedev’s book on Lysenko to me, and told me about the treatment of dissident scientists in the Soviet Union.
At this same time, I had enrolled in a French class. The university required that, in order to receive Advanced Placement credit in a given subject, students had to pass the next, higher-level course in that subject. I signed up for one course, with no intention of taking any more French—ever. Professor James Jones’s talent and charisma, however, changed my plans. I pursued (and almost completed) a second major in French that introduced me to many great thinkers from Diderot and Voltaire to, of course, Sartre and Camus. That endeavor also gave me some language skills that, even though badly rusted, later turned out to be very handy.
To complete the trifecta of my accidental preparation for this book, it also happens that I am a lifelong World War II history buff. I had read scores of books on the conflict and visited many key battlefields and museums without the slimmest notion of ever writing about the subject.
These ingredients simmered in the background for more than thirty years as I pursued my career as a biologist. I have admired Jacob and Monod’s scientific work since my graduate school days, and my own research on the genetic control of animal development and evolution has in some ways followed in their footsteps. But when I read brief mentions that Monod was “in the Resistance” and that he was “friends with Albert Camus,” or that Jacob was nearly killed in Normandy, I became curious to know what was left untold. How did their war experiences shape their future work and worldview? What did being in the Resistance entail? What was daily life like for Monod during the Occupation of France? Over many years, the questions expanded: What drew Monod and Camus together? How close was their friendship, and what did it mean to each man? What common ground did the writer-philosopher and the scientist find?
I had to know more.
Eventually, I was able to track down and meet some of the people who could tell me the answers, and so began one of the most exciting and gratifying adventures of my life. Indeed, I could not have told any of this story without the generous assistance and, most important, the trust of several extraordinary individuals who appear in it. In particular, I am indebted to Agnes Ullmann for sharing the story of her daring escape from Hungary, and for putting me in touch with many people connected to Monod and Jacob; to Geneviève Noufflard for permitting me to relate stories from her unpublished memoir of the war years, and for sharing numerous original documents from the Resistance; and to Olivier and Philippe Monod for giving me access to troves of private family letters, documents, and photos, for helping me understand their significance, and for sharing the story of their remarkable father and family. It has been a great privilege to meet such extraordinary people, and an honor to be welcomed into their homes.
Many others in France have also provided vital assistance. The exceptional dedication and efforts of the late Madeleine Brunerie, Monod’s longtime secretary, has preserved decades of invaluable documents at the Archives of the Institute Pasteur. There, I benefited enormously from the generous assistance of Dominique Dupenne and Daniel Demellier of the Service des Archives de L’Institut Pasteur, who went far out of their way to accommodate me during my visits and to help locate large numbers of critical dossiers.
I also thank Marcelle Mahasela of the Fonds Albert Camus, Bibliotheque Méjanes, Aix-en-Provence, for her assistance in obtaining materials, and Catherine Camus for her permission to quote several original letters and numerous passages of her father’s writings.
Special thanks to Isabelle Tarisca of the Cabinet du Préfet of the Préfecture de Police in Paris for her assistance in locating police files related to the Nordmann case, as well as Jacques Monod’s participation in the Resistance in 1940. I also thank Liora Israel and Julien Blanc for correspondence relating to the existence of these files. Thanks also to Severine Maréchal and the staff of Le Centre de Documentation et de Recherche du Memorial du Maréchal Leclerc–Musée Jean Moulin in Paris for generous access to their collections.
Many individuals generously agreed to be interviewed for the book or responded to written queries. Many thanks to the late Tamás Erdös, Madeleine Brunerie, Françoise Benhamou, Yves-Marc Achenbaum, Melvin Cohn, Georges Cohen, Donald Brown, David Hogness, Stuart Edelstein, and Arthur Pardee for their generosity.
I also had the benefit of interviews conducted long ago. I thank Olivia and Nicholas Judson for graciously granting access to transcripts of interviews produced by their late father, Horace Freeland Judson, in the cours
e of his writing The Eighth Day of Creation, the definitive history of the early history of molecular biology. I thank Charles Greifenstein, associate librarian and curator of manuscripts at the American Philosophical Society in Philadelphia, for providing the files.
Closer to home, I am deeply indebted to several individuals who provided crucial assistance to the project. Dr. Héloïse Dufour, a member of my laboratory at the University of Wisconsin, was a guide, translator, interpreter, and researcher throughout the development of the book. Her assistance in navigating Paris and its institutions, conducting or assisting with interviews and meetings, initiating correspondence, unearthing information in various archives, and deciphering key documents has been immeasurable. Her knowledge of French history, culture, and customs helped to open doors to many rewards.
Dr. Benjamin Prud’homme, a former member of my laboratory, catalyzed the launch of this project by locating Geneviève Noufflard and conducted a pivotal initial interview with Mme. Noufflard.
Throughout the preparation of the book, I have been assisted by Megan Marsh-McGlone, who tracked down countless books and articles, shouldered the Herculean task of curating the bibliography and sources in the book, as well as securing permissions for illustrations and the quoting of copyrighted material. And thanks to Leanne Olds for preparing the illustrations.
I have been very fortunate to have the attentive guidance and encouragement of my agent, Russ Galen, throughout the conception, development, and writing of the book. Special thanks to my editor at Crown, Domenica Alioto, for championing the book, and for her thoughtful input throughout the editing process. I am also especially grateful to Héloïse Dufour, Megan Marsh-McGlone, Steve Paddock, and Jim Carroll, who provided detailed feedback on earlier drafts.
This book would not have been undertaken without the unwavering support, encouragement, and understanding of my wife, Jamie Carroll. Jamie not only put up with my ramblings but also read every word of the first draft of the book, identified the thickets and brambles, and made countless great suggestions. No amount of Parisian chocolate can express my love and gratitude.
NOTES
Documents obtained from the archives of the Pasteur Institute Paris are documented as follows: item, date, location, Fonds, SAIP.
All archival letters originally in French are translated by either Sean B. Carroll (SBC), Héloïse Dufour, or both.
Interviews were conducted by the author unless otherwise noted.
PROLOGUE: CHANCE, NECESSITY, AND GENIUS
1 On October 16, 1957: Todd (1997), 371.
2 “One wonders whether”: Lottman (1979), 601.
3 “My dear Monod”: Letter, A. Camus to J. Monod, 11/18/1957, courtesy of Olivier Monod.
4 “I have known only one”: Brunerie (2008), 162.
5 “Frenchmen, the French Resistance”: Camus (2006), 9; Combat 58, July 1944.
6 “at least share”: Camus (2006), 2; Combat 55, March 1944.
7 “Four years ago”: Camus (2006), 17; Combat, August 25, 1944.
8 “To risk one’s life”: Bernard (1967), 173.
9 “those accidents which”: Aronson (2004), 36.
10 the talk of Paris: Ibid., 46.
11 “judging whether life”: Camus (1991a), 3.
12 “Being aware of one’s life”: Ibid., 62–63.
13 “The first teaches him”: Ibid., 66.
14 “the struggle towards”: Ibid., 123.
15 “One must imagine”: Ibid.
16 “In the depths of winter”: Ibid., 202.
17 “between hell and reason”: Camus (2006), 237.
18 “Camus taught me”: “Roger Grenier: Camus m’a appris des raisons de vivre,” NouvelObs.co, January 4, 2010.
19 “the most elevating form”: Jacob (1988), 274.
20 “an admirable conjunction”: Aronson (2004), 37.
21 “made things that were”: Judson (1979), 22.
22 “taste” and “elegance”: Cohn, as quoted in Ullmann (2003), 93.
23 “ideological terrorism”: Medvedev (1971), Monod preface.
24 “make his life’s goal”: Cohn, as quoted in Ullmann (2003), x.
25 “Never lacking in courage”: Crick, as quoted in Ullmann (2003), 23.
26 “The urge, the anguish”: Monod (1969), 19.
CHAPTER 1: CITY OF LIGHT
1 well below freezing temperatures: Le Matin, January 1, 1940; Le Figaro, January 1, 1940.
2 “extremely powerful bombs”: Letter, A. Einstein to F. D. Roosevelt, August 2, 1939, Manhattan Project Heritage Preservation Association, Inc. Available at http://www.mphpa.org/classic/COLLECTIONS/MP-Einstein~Sachs/Pages/Einstein-Sachs-001.htm.
3 “Par precaution”: Song: “Paris Sera Toujours Paris.” Words by Albert Willemetz, music by C. Oberfeld, 1939.
4 “I return with”: Shirer (1969), 403.
5 “There is not a woman”: Ibid., 404.
6 “We can never deal”: May (2000), 182.
7 “There is nothing more”: Ibid., 187.
8 “We should not devote”: Ibid., 187.
9 “War has been imposed”: L’Intransigeant, September 2, 1939, cited in Shamir (1976).
10 “The Nazis have compelled”: Le Populaire, September 4, 1939, cited in Shamir (1976).
11 “the modern Attila”: La Croix, September 3, 5, and 6, 1939, cited in Shamir (1976).
12 “brilliant attack”: Le Figaro, September 10, 1939.
13 “Throughout this night”: Le Figaro, January 1, 1940.
CHAPTER 2: PLANS
1 “Since France, the deadly enemy”: Hitler (1939), 14.
2 “The year 1939 was so dramatic”: Goebbels (1939).
3 “On September 2”: Ibid.
4 “It would be a mistake”: Ibid.
5 “harangue”: Le Matin, January 1, 1940.
6 “How can anyone believe”: Shirer (1969), 186.
7 “must go into Belgium”: Ibid., 185.
8 “It is impenetrable”: Ibid.
9 “the whole operation”: Ibid., 581.
10 “The enemy would take”: Ibid., 555; De Gaulle (1964), 29.
11 “At the end of”: McIntire and Burns (2008), 339.
12 The Pourquoi-Pas? sank: Debré (1996), 71.
13 “There will be no war”: Letter, Jacques Monod to his father and mother, August 31, 1939, private archives, Monod family.
14 “I would like to raise”: Ibid.
15 He wanted to serve: Letter, Jacques Monod to Odette Monod, January 15, 1940, private archives, Monod family.
16 So, rather than waiting: Letter, Odette Monod to Lucien and Charlotte Monod, January 31, 1940, private archives, Monod family.
17 If he was accepted: Letter, Jacques Monod to Odette Monod, April 15, 1940, private archives, Monod family.
18 Odette approved of the whole idea: Letter, Odette Monod to Lucien and Charlotte Monod, January 31, 1940, private archives, Monod family.
19 In February, Monod learned: Letter, Jacques Monod to Odette Monod, February 7, 1940, private archives, Monod family.
20 “I demonstrated dizzying panache”: Letter, Jacques Monod to Odette Monod, February 29, 1940, private archives, Monod family.
21 “The laboratory has been”: Letter, Jacques Monod to Philo Monod, January 9, 1940, private archives, Monod family.
22 “Should one accept life”: Todd (1997), 21.
23 “They have all betrayed us”: Camus (1963), 139.
24 “Never have left-wing”: Todd (1997), 89.
25 “For my works”: Ibid., 95.
26 “Why must one love”: Ibid., 97.
27 The issue on Camus’s day: Todd (1996), 238.
28 “Now that everything”: Camus (1963), 176–77.
29 “to arouse, reassemble”: Shirer (1969), 553.
30 “The ironfields”: May (2000), 338.
31 “When we embarked”: The Times, April 5, 1940.
CHAPTER 3: MISADVENTURES IN NORWAY
1 At
two a.m. on April 3: Haarr (2009), 66–69, 81–84.
2 The mining took place: Ibid., 90–95.
3 A Polish submarine: Ibid., 97–99, 135–36.
4 “You are wrong”: Shirer (1969), 561.
5 “Will the lesson”: Le Figaro, April 10, 1940.
6 After the successful troop landings: Haarr (2009), 342–71.
7 “The situation is thus better”: Le Figaro, April 10, 1940.
8 “It would be absurd”: Shirer (1969), 556.
9 “defensive on land”: Ibid.
10 “It is extremely doubtful”: Ibid.
11 “Have you been”: Liebling (2008), 587.
12 “Don’t worry about me”: Letter, Jacques Monod to Odette Monod, April 16, 1940, private archives, Monod family.
13 “Except for rotten luck”: Letter, Jacques Monod to Odette Monod, April 15, 1940, private archives, Monod family.
14 “Training started seriously”: Letter, Jacques Monod to Odette Monod, April 17, 1940, private archives, Monod family.
15 Jacques’s letters were unfailingly upbeat: Letters, Jacques Monod to Odette Monod, April 18, 19, 20, and 23, 1940, private archives, Monod family.
16 Jacques was able to confirm: Letter, Jacques Monod to Odette Monod, April 17, 1940, private archives, Monod family.
17 “I hope after the war”: Letter, Odette Monod to Lucien and Charlotte Monod, April 24, 1940, private archives, Monod family.
18 “I’ve been feeling very isolated”: Letter, Jacques Monod to Odette Monod, April 17, 1940, private archives, Monod family.
19 “What is happening”: Letter, Jacques Monod to Odette Monod, April 25, 1940, private archives, Monod family.
20 “Events are going”: Todd (1997), 105.
21 “You can’t live here”: Ibid., 102.
22 “I see the form”: Ibid., 88.
23 “a desperate man”: Ibid., 104.
24 “A novel is only philosophy”: Ibid., 84.
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