After the Center was shut down, Jacob decided that biological research would suit him. The big question was: What field to study? With the eruption of the Lysenko controversy, genetics had acquired a special prominence. Rather than turning French scientists away from Mendel and Morgan, as Soviet biologists were forced to do, the controversy attracted some aspiring scientists toward genetics. Jacob became one of them. At one meeting on Lysenko, Jacob spotted and introduced himself to Monod.
Jacob thought it was incredible that Lysenko had obtained the full support of the Soviet government and press to prohibit “the teaching and practice of one of the most solidly established sciences” and “to impose an idiotic theory on biology.” He was astonished that free intellectuals like Louis Aragon would enslave themselves to ideology. He resolved to study heredity. For Jacob, “Studying genetics meant refusing to substitute intolerance and fanaticism for reason.”
The problem was that at the time of his epiphany, Jacob had no idea how he—a complete novice, and approaching thirty to boot—might get into the field. Naïve in the ways of academia, he started by knocking on doors. He presented himself to the director of life sciences at the National Center for Scientific Research and declared his desire to devote himself to learning genetics. He was politely refused. He then went to the director of the National Hygiene Institute. Same result.
But at the Pasteur Institute, Director Jacques Tréfouël took an interest in Jacob’s war experience and let on that the Pasteur was deeply involved in the Resistance. Then he offered Jacob a research fellowship.
Jacob was thrilled. Of all places to learn and work—the Pasteur Institute!
He accepted on the spot. He started in October 1949 by enrolling in the “Great Course”—an overview of microbiology, virology, and immunology taught by the eminent staff of the institute. In order to get to real research, however, he had to find a supervisor willing to take him on. He learned that in the area of genetics, there were two people to consider: Jacques Monod and André Lwoff. He had briefly met both, Monod at the Lysenko meeting, and Lwoff at the Penicillin Center, and decided that Monod was the less intimidating. He went to see Monod, who told him, “I have no space. And anyway, I am not the boss. Go see Lwoff.”
Jacob made an appointment to see Lwoff. He navigated his way around the equipment cramping the corridor of the attic of the Chemistry Building and presented himself to the senior scientist, who was sitting eating his lunch. Jacob made his case, telling Lwoff how much he wanted to study genetics. Lwoff pondered Jacob for a while, then said, “Impossible, I haven’t got the least space.”
Disappointed but undeterred, Jacob went back to Lwoff several times throughout the winter, and received the same answer each time. His hope nearly gone, he made one last appeal in June 1950. This time, before Jacob could recite his request, Lwoff told him excitedly, “We have just found the induction of the prophage.”
“Oh,” Jacob said. He had no clue what Lwoff was talking about.
“Would you be interested in working on this phage?” Lwoff asked.
“That’s just what I’d like to do,” Jacob said.
“Then go off on vacation and come back the first of September,” Lwoff told him.
He was in. Not only had Lwoff accepted him, but he would be no more than forty feet away from Monod, who occupied the laboratory at the other end of the corridor. Jacob went immediately to a bookstore to look up “prophage,” but had no luck. He had no clue what he was getting into.
UPON JOINING THE lab late that summer, Jacob realized right away that Lwoff was not exaggerating about space. The attic was cramped, and it was hot. The bacteriologists did not want to open any windows and have microbes blowing around. He was assigned to share a laboratory with two Americans at Lwoff’s end of the corridor.
His immediate instinct was to find his place in the laboratory’s and Pasteur’s culture—to get to know the people, learn the hierarchy and the rituals, and then start grappling with the science for which he had no academic background whatsoever. The first cultural issue was language. His two American lab mates wanted to speak French, and Jacob wanted to develop his English, so they compromised: they spoke French in the morning, English in the afternoon.
His boss, “le patron” Lwoff, was a tall, refined person who dressed well and knew about wines, art, and language. He spoke and wrote carefully and precisely. He expected and enforced good French and good grammar throughout the floor, regardless of the nationality of the speaker. He was to be addressed by everyone, Jacob included, as “Monsieur.” Yet, despite his formality, Jacob found Lwoff to be very warm, kind, and always encouraging.
Monod, however, was a different personality. With his high cheekbones, firm chin, and wavy black hair, Jacob thought Monod looked “like a cross between a Roman emperor and a Hollywood movie star.” And Monod did not go for formalities. When Jacob called him “Monsieur,” Monod asked him not to. Instead, he said, “Call me what you like, Monod or Jacques or old fart.” Jacob chose Jacques.
The workday was divided by the lunch hour that, in the tradition introduced by Monod, was a free-for-all. The banter included ideas, jokes, scientific gossip, insults for Lysenko and his French supporters, and a discussion of Stalin, literature, films, and more. To Jacob’s regret, however, the festivities took place around a large table in the middle of his lab, so experiments had to be suspended from one to two o’clock every day. The ritual ended with everyone sipping a strong coffee before going back to experiments.
Another rite with which Jacob was completely unfamiliar was the research seminar. The attic’s inhabitants squeezed into Lwoff’s office and sat on stools and chairs while one researcher or a visiting scientist stood in front of a movable chalkboard, presenting their latest results and ideas. The exercise was unlike any lecture he had witnessed, because the speaker was interrupted and peppered constantly with questions, comments, and challenges. In the back-and-forth between scientist and audience, alternative interpretations were floated and new experiments were suggested, and then subjected immediately to the group’s scrutiny.
The questioning could be withering. The research seminar was a crucible that tested the confidence, creativity, logic, and quick thinking of every participant. Jacob soon learned that Monod was a master of the form—a form that to Jacob appeared akin to a bullfight, with Monod playing the role of toreador and flaunting the cloth of an argument for others to charge before plunging in his sword.
The greatest ritual of all turned out to be an annual affair that took place at the end of each September, when the entire Institute gathered to mark the anniversary of the death of their great founder, Louis Pasteur. Lwoff told Jacob, “You should go, once, just to see.” Jacob joined the streams of Pasteur employees leaving the laboratories, the scientists as well as the cleaning personnel, who were amassing in a large hall. A floor mate started to point out the faces of the most eminent at the head of the line. The oldest sported white goatees and black skullcaps that harked back to Pasteur’s time and his first pupils. Jacob saw seventy-eight-year-old M. Camille Guérin, who was the codeveloper of the tuberculosis vaccine known as BCG (he was the “G” in Bacille Calmette-Guérin); others behind him were renowned experts on various microbes and diseases, from tetanus to plague. Jacob understood that “every germ had its representative”—one expert in France for each particular disease.
Suddenly, a hush came over the crowd as the director addressed them, recalling the traditions and achievements of the institution. Then, in silence, the procession into Pasteur’s tomb began with the director and trustees in front, the most senior and distinguished scientists second, the heads of laboratories after them, and so forth until the maintenance and kitchen personnel descended through great wooden doors and down the marble steps to the mosaic floor of the tomb. Decorated with green branches of laurel and oak, Pasteur’s deep-green sarcophagus of Swedish marble lay in the center. Overhead, Jacob saw colorful mosaics depicting various scenes relevant to Pasteur’s lif
e—a boy being bitten by a dog, sheep grazing, garlands of hops, and grapevines representing his achievements in rabies, anthrax, and fermentation, respectively. On the walls were more scenes of Pasteur’s victories. Stirring vignettes, to be sure, but to Jacob the grandeur of the mausoleum seemed more befitting Napoleon than a scientist.
Leaving the tomb for the gardens above, Jacob reflected not just on Pasteur’s science but on the institution he had created and the unique type of scientist he had cultivated—the Pastorian. Here, recruited from all over the world, were doctors with no patients, pharmacists with no drugstore, professors with no classrooms, and chemists with no industry. It was a cathedral of science—a monastery, really—with its monks devoted to the special calling of research.
Jacob began to wonder how many of those around him had achieved or would achieve their goals. How many years does it take to discover something meaningful? How long before one knew whether one was on the right or the wrong track, whether one had the sort of vision and talent that would merit being at the front of the procession he had just witnessed?
Ten years after leaving for England, a lost decade in terms of his profession, he was starting over from scratch. A mere beginner at age thirty. What were his chances of success, of such glory?
He gave himself five years to find out.
DATA OVER DOGMA
Pasteur’s shrine was not used exclusively for grand ceremonies. Finding that his desk in Monod’s laboratory was too poorly lit for him to work at night, Melvin Cohn discovered that the tomb was very well lit. With the collusion of the building’s concierge, the mausoleum was left unlocked for Cohn in the evenings. He would then spread out his papers using Pasteur’s sarcophagus as a desk and study late into the night. Monod was startled to find Cohn there one evening when he was taking some visitors around on a tour. But he did not reprimand Cohn for such sacrilege; Monod also found the ambiance rather congenial, and the two men spent many evenings together “chatting across the death mask of the Institute’s patron saint.”
Cohn and Monod had much to discuss. Shortly after Jacob’s arrival in the attic, Monod’s team hit a streak during which they acquired a series of new and important results. The experiments provided a large step forward in understanding the phenomenon of enzyme adaptation. But they also had the added virtue of demolishing the Lysenkoist slant on nature in the same blow. One of the ironies of Monod’s involvement in the Lysenko matter was that the very phenomenon that he had been studying for more than a decade itself gave the outward appearance that organisms could change readily in accordance with their environment: that is, after some delay, bacteria grew when given an alternative to their preferred sugar glucose. The response appeared as though the bacteria had acquired a new ability that was provoked by the presence of the alternative sugar. The phenomenon could be viewed from the Michurin-Lysenko perspective as evidence that organisms were readily adaptable to whatever conditions they encountered. (It was akin to the notion, promoted by the nineteenth-century naturalist Jean-Baptiste Lamarck, that giraffes acquired long necks by reaching for their food.)
In biochemical terms, what Monod’s team knew was that the sugar lactose, a disaccharide composed of the two sugars galactose and glucose, could not be utilized by E. coli bacteria unless it was broken down by the enzyme ß-galactosidase into those two sugars. Moreover, that enzymatic activity was not detectable unless cells were grown in the presence of lactose. It appeared as though the lactose molecules somehow “instructed” cells to produce the specific enzyme that was needed. How a specific enzyme was made was therefore the central mystery.
Monod had an idea. He proposed that bacteria cells contained a common set of protein building blocks for making a variety of enzymes, and that these blocks were brought together in different combinations by different sugars to make different specific enzymes. The sugars competed for the building blocks so that, for example, if glucose was present, enzymes for using glucose were assembled instead of enzymes for breaking down lactose. The central feature of Monod’s model was that the sugar to be acted upon, what is called the substrate of the enzyme, provoked the formation of the correct enzyme.
Cohn and Monod developed a clever test of this idea by synthesizing a large number of chemically modified forms of lactose. The straightforward prediction of Monod’s model was that compounds that were good substrates for the ß-galactosidase enzyme would provoke the formation of the enzyme, and those that were not good substrates for the enzyme would not. That was not at all what the results showed. Monod’s team found that certain compounds that were not substrates could elicit enzyme activity, and certain other compounds that were good substrates did not elicit enzyme activity. Monod’s model was wrong—and he was delighted.
Monod knew that progress was made when previous ideas, even one’s own, were vanquished and new ones had to be formulated and tested. And he was very confident in his abilities to come up with new ideas and new experiments.
Moreover, regardless of how enzyme adaptation actually worked, Monod’s results punctured the Lysenkoist balloon. In his laboratory in the Pasteur’s attic, bacteria made large amounts of an enzyme in response to sugars they could not use, and failed to make an enzyme in response to sugars they could use. Contrary to the Michurin-Lysenko theory, these bacteria were not adapting in accordance with their environment. Cohn, who attended meetings of the Michurin-Lysenko Society with Monod, noted with satisfaction how the absurd Soviet theories that had so irked Monod “had been answered with experimental vengeance.” The corpse of Lysenko’s fantasies had been buried—with sugar.
In light of their results, Monod decided it would be best to banish the Lamarckian and Lysenkoist connotations of the term “enzyme adaptation.” The phenomenon was renamed “enzyme induction,” and the substances capable of inducing enzymes were called “inducers.” Monod’s team had shown that inducers were not always substrates for the enzyme and vice versa. The results with the modified sugars started Monod thinking that inducers and substrates may work through different means—that while the enzyme acted on the substrate, the inducer acted through something else. This would turn out to be a productive new line of thought.
In the meantime, Monod looked forward to talking about his new results and insights. He was invited to the United States in 1951 to speak at meetings of the American Chemical Society and the very prestigious Harvey Society of New York.
But he went to neither. Cold War politics caught up with Monod.
Following the usual procedure, Monod went to the American consulate in Paris to obtain a visa for his trip. He learned that, due to his previous membership in the Communist Party, he was an “inadmissible alien.” The year before, in the wake of the outbreak of the Korean War and rising fears about the influence of Communism, the US Congress passed the Internal Security Act of 1950. Among many measures designed to thwart “un-American and subversive activities” was a provision that aliens who “at any time, shall be or shall have been” members of Communist parties were to be excluded from admission into the United States.
The American consul advised Monod that he could apply to the attorney general of the United States for special permission to enter the country. Monod decided against doing so, and explained himself in a letter to the consul (composed in English):
In view especially of your extremely courteous and helpful personal attitude in this matter, I feel that I should explain in some detail the reasons which should have led me to this negative decision. These are twofold.
To begin with my proposed trip to the U.S. was planned, you may recall, in answer to invitations extended to me by the American Chemical Society and by the Harvey Society. However much I appreciate the honour entailed in these invitations, as well as the pleasure and fruitfulness of a scientific visit to the U.S., I cannot put these in balance with the extremely distasteful obligation of personally submitting my “case” to the Department of Justice, and of having to ask for permission to enter the U.S. as an exceptional and
temporary favor of which I am legally assumed to be unworthy.
The second reason is that I am not willing to fill in and swear to any “biographical statement” of the type apparently required for the application. This refusal is not based on abstract principles only, but on a sad and terrible experience: this kind of inquisition was introduced into the French Administration under the occupation. I will not submit myself to it, if I can possibly avoid it … You will also realize, I believe, that such statements, should they fall into the wrong hands, might conceivably be used as a source of information. The mere possibility of this would make it impossible for me to submit one, even though I knew that mine would be uninteresting. The fact that I have been completely estranged from my former political affiliations makes this even more impossible.
That being said, I should like to add that I did not reach this decision light-heartedly, as I fully realize that it means cutting myself partially away from a country which I love, and to which I am attached by very strong links. Not only am I half American [Monod’s mother was from Milwaukee, Wisconsin], but I have many very close friends in your country. I have learned by experience to respect and admire American Science. Indeed I owe much to several American scientific or other institutions, such as the Rockefeller Foundation and I may venture to say that, as a scientist, I have had more recognition in the U.S. than in my own country.
However, all this is strictly personal and I would like to mention another more general aspect of these problems. Scientists themselves are quite unimportant. But Science, its development and welfare are overwhelmingly important, isolation is the worst enemy of scientific progress (if proof of this statement were needed I would point to the strange and profound deterioration of Russian biology in recent years). Measures and laws such as you are now obliged to enforce will contribute in no small extent to erecting barriers between American and European science. I do not pretend to know whether or not such measures are justified in general, and in any case I have no right to express an opinion. But I can say, because it is a plain fact, that such measures represent a rather serious matter to the development of science, and that, to that extent at least, they must be contrary to the best interests of the United States themselves.
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