A SURPRISE BESTSELLER
Le Hasard et La Necessité appeared in France in October 1970 with the public reception of his essay very much in doubt. Who would read a book whose middle five chapters were laden with technical description, one that needed an appendix with chemical diagrams to boot? And who was eager to hear his message that all religious systems were imaginary constructions? What’s more, Monod had taken a considerable risk to his reputation by straying onto the turf that some philosophers and most theologians would no doubt feel was reserved for themselves.
The book was a sensation.
It struck chords, and nerves, across France and quickly became a bestseller. Almost 200,000 copies were sold in the first year, and for many weeks Chance and Necessity trailed only the French translation of Erich Segal’s Love Story at the top of book sales. Foreign translations quickly followed, and the book was a bestseller in Germany and Japan as well.
The book garnered scores of reviews in France alone, as well as reviews of its English translations in The Economist, Atlantic Monthly, LIFE, and Newsweek. Monod received two reviews in the New York Times, which also published two interviews with him.
The critics ran the gamut from condemnation to high praise. Few were neutral. Not surprisingly, various clergy and church representatives protested, as did the Communists in L’Humanité. Most writers were ill-equipped to understand, let alone to debate, Monod’s core scientific argument about the role of chance in humans’ biological origins. Most criticism therefore focused on denying the implications for religious thought, and on questioning Monod’s authority and reasoning on ethical matters.
Less partisan writers, however, lauded the book. Said one reviewer in Le Figaro, “I read Jacques Monod with the same passionate and anxious attention as I would a book brought from a faraway star and from which the author was, for millions of years, the clear and careful witness of the birth of life and of humanity on our Earth.” The same reviewer, though he did not agree with all of Monod’s conclusions, praised “the depth of his sensibility, the lucidity of his experience, and the force of his courage.” Another reviewer wrote, “Even the most cautious reviewer, however nervous of debasing the currency of adjectives, must sometimes use the word great. This is a great book, sinewy, lucid, and intelligible.”
The success of the book and the extensive press coverage created great demand for radio, television, and newspaper interviews, which gave Monod the opportunity to clarify his positions, to extend his arguments, and to acknowledge again Camus’s influence on the larger message of his essay. One common lament was the perceived pessimistic message of the book, that Monod’s vision was too cold, too austere. One interviewer asked Monod: “One could ask oneself effectively why live, why have children only in order to condemn them to death, why this thirst for knowledge?”
“On that, I do not have an original response to this question,” Monod answered. “I will answer you with the citation that I put at the beginning of my book and that I will ask you to read because I meet Camus exactly on this text, which is admirable besides.”
The interviewer read Monod’s epigraph from The Myth of Sisyphus. He then said, “This text is admirable but it does not provide what I would call the pedagogical means to arrive at serenity.”
Monod countered, “Myself, I do believe that it does, I do believe that it does; I believe that it provides the only means.” He continued, “I believe that it provides that so long as one demonstrates the grandeur of this idea. I believe that man has a need above all, he has a need for transcendence. And there is, in the existential attitude of the kind that Camus has offered to him, a deliberate transcendence … that I find so beautiful that it ought to be acceptable.”
LAST WORDS
The success of Chance and Necessity surprised no one more than Monod himself. However, he was not able to enjoy it fully. A few months after publication, Odette was diagnosed with terminal cancer. At the time of her illness, Monod had been contemplating taking a sabbatical abroad, or even going on a long sailing voyage. Instead, he took on a new challenge that would keep him near home and able to support Odette—he became the eighth general director of the Pasteur Institute. Monod’s parents had once speculated whether their talented, promising son would become the next Beethoven or the next Pasteur. He had now joined a short, direct line that reached back directly to the great scientist.
When the Institute celebrated the founder’s 150th birthday in 1973, the honor fell to Director Monod to offer a few words about Pasteur. The celebrated scientist, author, statesman, and philosopher could have been speaking of himself when he said:
Where does genius come from? Often we are contented with attributing it to a unique, exceptional, and mysterious resource of mind. On the contrary, in the case of Pasteur, we see clearly that the power of his genius comes from multiple sources, very much in opposition to his intelligence, character, and temperament. He was an artist and a dreamer. He would allow himself to be fascinated by mirages of an imagination that always tended to go beyond the horizons of knowledge. He was ambitious and dominating and would be satisfied only with real and complete victories. He was rigorous and demanding towards himself. At the same time he would spare no efforts to be severe and disciplined.
The years of his directorship, however, were difficult. Odette died just eleven months after her diagnosis, and the following year Monod became severely ill with viral hepatitis. He recovered, but his own inclination to be demanding and disciplined led to considerable contention. Monod had accepted the leadership of the Pasteur out of a great sense of duty and debt to the institution, which had allowed him to pursue a style of science that was not possible elsewhere in France. The Institute was facing severe fiscal challenges that threatened its survival. Monod hurled himself into the task of saving the Pasteur, which led him to instigate major operational and structural changes that displeased several formerly close colleagues.
The burden of administration forced Monod away from his own science, and he missed the close rapport he had with his scientific team. A couple of years before the end of his six-year term, Monod decided that he would not seek reappointment as director. He wanted to return to creative pursuits. He told Agnes Ullmann, still at the Pasteur fifteen years after her escape from Hungary, that he was thinking of writing a new book entitled Man and Time (L’Homme et Le Temps).
In late 1975, however, he developed aplastic anemia, a condition in which the body fails to replenish red blood cells. His prognosis was dire. Although easily fatigued, he continued his duties as director, sustained by frequent blood transfusions.
Despite all of the competing demands on his time, and his illness, Monod found moments to reply to correspondence that came from many different quarters. In January 1976, a handwritten letter arrived from Grenoble:
Sir,
I am a thirteen year-old boy who is very interested in research. I know that you are one of the greatest researchers in the world (our professor of science told us so).
Excuse me for bothering you, but I would like to know what maxim guides your life. Perhaps I could apply that when I grow up.
Could you also send me a signed photo of yourself so that I can display it in my bedroom …
Good-bye M. Monod and Happy New Year 1976.
Bruno
Monod replied:
My Dear Bruno,
Thank you very much for your letter that has interested me a great deal. However, you have posed a difficult question because I do not think that one can find one maxim that, alone, allows one to conduct an entire life and to govern the sometimes painful choices with which one can be confronted.
All I can tell you are the qualities that appear most important to me. If one were to pose this question to me, I would reply without a doubt that they are: courage, as much moral as physical, as well as the love of truth, or rather, the hatred of lies.
I prefer to speak of the hatred of lies rather than the love of truth, since one is never sure of holding
the truth, whereas with lies, one is almost always able to detect them, to discover them, and to denounce them.
As you requested, I am sending you a signed photo.
Thank you for the New Year’s wishes. Happy New Year and good wishes to you.
Jacques Monod
The disease symptoms waxed and waned. Feeling better in May 1976, Monod went to Cannes to spend a weekend relaxing at the Monod family home with friends. On Thursday, May 27, he went to a reception at the famed film festival with author Jerzy Kosiński, whose book Being There was published at the same time as Chance and Necessity, and whose lead character was named Chance. Monod, in black tie and light-colored jacket, was his usual elegant and charming self. He enjoyed drinking, smoking, and joking with the other party guests.
The next day, Friday, Monod chatted on the phone with Ullmann in Paris about his upcoming travel plans to a meeting in the States and a research paper they were working on together. They would continue their conversation when Monod returned to the Pasteur after the weekend. “See you Monday in the lab,” he said.
Ullmann was entertaining dinner guests at home Sunday night when the phone rang. It was Philo calling from Cannes; he told her that Jacques had been hospitalized and that his condition was grave. She would need to come quickly.
Ullmann, Erdös, and Monod’s sons, Olivier and Philippe, raced to Cannes. Olivier and Philippe took the overnight train; Ullmann flew early the next morning.
AT THE HOSPITAL in Cannes, Monod’s cardiologist and Philo were keeping a close watch as Monod battled for his life.
Philo heard his brother say very faintly between breaths, “Odette … Pasteur …”
Then, after a pause, “Je cherche à comprendre” (I am trying to understand).
He never regained consciousness.
After his funeral, a few rough pages of Man and Time were found on his desk.
APPENDIX: THE SCIENCE
MONOD’S AND JACOB’S critical observations, discoveries, and ideas are spread over many pages in this book. Since most readers are not biologists, I thought it might be helpful to provide a short summary of the relevant science that could be consulted to refresh certain points. This information is divided into (1) what was known about genes, DNA, and proteins as they began their work; (2) Monod’s and Jacob’s discoveries that are covered in the book; and (3) important subsequent, related discoveries.
GENES, DNA, AND PROTEINS
CHROMOSOMES AND GENES
From the pioneering work by Thomas Hunt Morgan (Nobel Prize 1933), it was known that chromosomes are the physical entities responsible for heredity, and that specific genes reside at specific positions along chromosomes. Oswald Avery’s studies (1944–1946) demonstrated that deoxyribonucleic acid (DNA) is the chemical component of the chromosome responsible for inheritance. Each chromosome contains a long molecule of DNA.
DNA
James D. Watson and Francis Crick deciphered the structure of DNA in 1953. DNA molecules in cells are made of two strands of four distinct bases. These chemical building blocks are denoted by the single letters A, C, G, and T. The strands of DNA are held together by strong chemical bonds between pairs of bases that lie on opposite strands—A always pairs with T, C always pairs with G—as shown below:
Solving the structure of DNA immediately revealed how the two fundamental processes of inheritance and mutation worked at a molecular level. That is, a DNA sequence could be faithfully copied and passed on because the base present at each position on one strand determined its complement on the other strand. Mutations result from errors in this copying process, where the wrong base or an extra base(s) gets inserted, or a base(s) may be deleted, generating a change in the DNA sequence.
PROTEINS
Proteins are the molecules that do all of the work in cells, breaking down nutrients, assembling cellular components, copying DNA, and so on. Proteins are made up of chains of building blocks called amino acids. There are twenty different amino acids. The chemical properties of these amino acids, when assembled into long chains averaging about 400 amino acids in length, determine the unique activity of each protein. Enzymes are proteins that catalyze specific chemical reactions.
At the time of Monod’s and Jacob’s seminal work, the relationship between the sequence of bases in DNA and the sequence of amino acids in proteins was not understood. Crick asserted that the main function of DNA was to encode proteins, but how that information was decoded and the nature of the “genetic code” were unknown (Crick’s black box) until the early 1960s.
MONOD’S AND JACOB’S DISCOVERIES
DIAUXY
The observations that started Monod on the path to fundamental insights and the Nobel Prize concerned the growth of bacteria in the presence of simple sugars. When bacteria are grown in the presence of a single sugar, such as glucose, they grow exponentially until the sugar is exhausted. But Monod noticed that when bacteria were grown in the presence of certain combinations of two sugars—glucose and lactose, for example—they grew exponentially, then paused briefly before resuming exponential growth. He called this phenomenon “double growth” or “diauxy.” By shifting the relative ratios of the sugars, he found that he could shift the relative length of each part of the double growth curve. From that observation, he deduced that the bacteria were using up one sugar before utilizing the second, less-preferred sugar.
ENZYME ADAPTATION AND ENZYME INDUCTION
The time lag in bacterial growth on a less-preferred sugar was interpreted as an example of “enzyme adaptation,” in which growth is delayed briefly until the enzyme required to break down a nutrient appears.
Monod specifically focused on the control of lactose metabolism. Lactose is a disaccharide made up of the two monosaccharides glucose and galactose. Lactose itself cannot be used as an energy source in E. coli bacteria; it must be broken down into glucose and galactose, which is the function of the enzyme ß-galactosidase. Importantly, the enzyme is normally not produced in the absence of lactose, but appears when lactose is the sole energy source provided to the bacteria (a case of enzyme adaptation). Since the appearance of the enzyme occurred in the presence of the sugar it broke down, Monod and others renamed the phenomenon “enzyme induction,” and substances that were able to elicit the enzyme were dubbed “inducers.”
THE LACTOSE OPERON
How a simple bacterium “knew” which sugar to use, and when to produce ß-galactosidase—were the crux of the mystery Monod set out to solve.
Crucial to his progress was his decision to tackle the problem using genetics. During the war, Monod and Alice Audereau found that strains of E. coli bacteria that were unable to utilize lactose occasionally gave rise to colonies that could grow on lactose, and that these colonies were due to genetic mutations. This was crucial evidence that the ability to metabolize lactose was genetically determined. Therefore, components of the enzyme-induction process could be identified through mutations.
In order to figure out where these mutations occurred on the E. coli chromosome, and to sort out how they affected enzyme induction, Monod teamed up with Jacob in 1957. Jacob had been studying a bacterial virus, or bacteriophage, called lambda. Jacob was a pioneer in developing methods for mapping bacterial genes. He was particularly interested in the phenomenon of lysogeny, whereby a virus hides out in a bacterial host but can be induced to emerge by certain treatments. Jacob proposed that enzyme induction and virus induction were analogous—that in each case a repressor kept genes off unless an inducer was present.
From 1957 to 1960, working with key collaborators such as Arthur Pardee, Monica Riley, and Sydney Brenner, Monod and Jacob identified several components involved in the control of lactose metabolism in E. coli, and coined several general terms that have remained in use to this day:
Structural gene, which encodes the structure of a protein, such as an enzyme
Regulatory gene, which governs the expression of a structural gene
Repressor, which turns off enzyme production,
such as the protein encoded by the i gene
Operator, the acceptor site for the repressor on DNA
Operon, a set of structural genes controlled by a common operator and repressor, and usually involved in the same biochemical pathway
Messenger RNA, an intermediate that carries information from genes in DNA to the ribosome for the synthesis of specific proteins.
Monod and Jacob figured out the logic of the genetic switch by deciphering what happened in certain mutants. For example, mutations in the repressor gene i disabled repression, but not if a second, normal, copy of the gene was present in the cell. Mutations in the operator (o) also disabled repression, regardless of whether another operator was present. Mutations in specific structural genes blocked the production of specific enzymes.
From these observations, they were then able to construct a general picture of the process of gene regulation that looked like the following:
Monod-Jacob General Model of Gene Regulation. The key to the genetic switch is the interaction of the inducer and repressor. Top, when no inducer is present, the repressor binds to and occupies the operator that lies adjacent to the structural genes A and B, keeping them switched off. Bottom, when an inducer is present, the repressor is inhibited from binding to the operator, allowing genes A and B to be switched on, leading to the production of messenger RNA that carries information for the synthesis of proteins A and B. The figure is modified from Jacob and Monod’s synthesis published in 1961. (Drawing by Leanne Olds)
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