Brave Genius

by Sean B. Carroll

  They briefly discussed the details. On the day of the operation, Ullmann and Erdös would have only a few hours’ notice to get ready. Helm was to come to Ullmann and say that he was in Budapest and would be at the rendezvous spot on the road between Budapest and Esztergom at a given time. Ullmann and Erdös would take a bus to the rendezvous. They would leave only with the clothes on their backs.

  THE OPERATION WAS slated for Saturday, June 18.

  Helm and his wife checked into a hotel in Budapest on the seventeenth. Helm then went to Ullmann to let her know that he had arrived and would see them at the rendezvous point. Ullmann and Erdös knew that their disappearance would arouse suspicions. In order to throw the secret police off their trail, they told some friends that they were going for a tour around a lake.

  They took the bus out of Budapest toward Esztergom and got off at the rendezvous point. Helm was not there. Ullmann and Erdös knew that timing was critical. It was a long drive to the Austrian border, and they had to reach it before dark.

  Finally, with Ullmann and Erdös waiting anxiously, Helm and his wife arrived in their car, pulling the camping trailer behind. Ullmann and Erdös got into the car. Ullmann took a tranquilizer, both to calm her nerves and to suppress any coughing once she was hidden in the camping trailer.

  Two hours before they reached the border, Helm pulled off the road. His wife took the two children for a walk and snapped their pictures along the Danube. Helm opened the camping trailer for Ullmann and Erdös.

  The inside of the trailer was large. It had a kitchen, a sitting room, a bathroom, and a bedroom with two beds. Helm had planned that Erdös and Ullmann would hide in compartments under each of the beds. When Ullmann saw the arrangement, however, she vetoed that idea right away, telling Helm, “I will not get in there. That’s the first place they will look.”

  There was not much time to arrange any alternative. Ullmann noticed a large box in the bathroom. She asked Helm, “What’s in this box?”

  “Just some things,” he replied.

  Ullmann asked, “Isn’t there enough space for two people?”

  Helm hesitated. “It is difficult.” Then, he decided, “Yes, it might be secure.”

  The box was a sort of closet. It was full of old clothes and towels, with a bathtub perched on top of it. It looked to Ullmann like the bathtub had not been used. Helm quickly threw the clothes and towels out of the trailer to make a space for Ullmann and Erdös. There was just enough room for the two stowaways to cram themselves in. They each had a small canteen of water and a straw through which to sip it. Ullmann covered her head with some white linen. Erdös said to Ullmann, “Don’t move, and don’t say anything until the last moment.”

  Helm closed the box, fixed the bathtub into place, returned to the car, and started for the border.

  AT THE BORDER, two customs officers stopped the vehicle. They told Helm that they wanted to see inside the camping trailer. Helm obliged while his wife stayed in the car.

  One officer had an electric light that he shone into each part of the camping trailer. He asked Helm about each of the rooms, “What’s this?”

  “The sitting room,” Helm replied.

  “And what is this?” the policeman continued.

  “The kitchen,” Helm answered.

  Ullmann and Erdös could hear the entire exchange. Ullmann’s heart was racing.

  “And what is this?” the officer asked.

  “This is the bathroom.”

  “You have a bathroom?” The policeman was surprised.

  “Yeah, we have a bathroom.” Helm added, “I’ll show you.”

  The bathroom was too small for both men to enter; Helm occupied almost the entire room and could barely move around.

  The officer pointed to the compartment under the bathtub. “What’s this in the bathroom, under the bathtub?”

  “Nothing,” Helm said. “Just a place where we store dirty things.” Helm knocked on the wood.

  “Now open it,” the policeman demanded.

  Helm pried it open half an inch. Ullmann realized that the beam from the officer’s light brushed her hand. She tried to pull it back gently. The officer did not see her but could see the white linens that Ullmann had used to cover her head. The officer wanted to know why the linens were in the space below the bathtub and asked Helm to dismantle the box.

  “I am not going to open it,” Helm protested, claiming that he had already opened it once while crossing into Yugoslavia. “I will cut into it for you,” he offered.

  Helm grabbed a saw and then made a big show of cutting into the compartment.

  “OK, enough.” The officer was satisfied.

  The officers next went into the bedroom and made Helm dismantle the beds—exactly as Ullmann and Erdös had predicted.

  Satisfied by their search, the officers left the trailer.

  Inside their compartment, Ullmann and Erdös felt the trailer start to move very slowly. But then it stopped again.

  Ullmann could hear the officer say some paperwork had to be fixed.

  After nearly an hour at the border, the trailer started moving again. Then, after a short while, Ullmann smelled gasoline. She knew there were no gas stations on the Hungarian side—they were in Austria!

  Once they were far enough from the border, Ullmann and Erdös, their limbs numb from being confined for hours, climbed out of their cramped hiding space and stepped into the fresh Austrian air, and freedom.

  It was night before the caravan reached Helm’s house, so the exhausted stowaways decided to sleep there. They called Monod and Kövesi to let them know they had made it out.

  MONOD SENT TELEGRAMS to Pardee in Berkeley, Jacob in Pasadena, Csapo in New York, and other supporters of the mission to spread the good news.

  When Madeleine arrived at the Pasteur on Monday morning, Monod was already there. He shouted out to her, “Agnes and Tom are in Vienna!”

  Madeleine was so overjoyed she could not help but run up to Monod and give him a kiss.

  A few days later, Monod received a letter from Ullmann in Vienna:

  You have organized something that appeared absolutely impossible. But you have not only organized it, you have always thought about all of the details. How many painful hours have you spent? I had remorse over stealing your time and energy. You are an extraordinary man. If I did not know that you really existed, I would imagine that you were a fiction who exists only in dreams. There are some things for which one can never thank someone enough and never forget. I cannot yet fully appreciate what it means that I am free … free thanks to you.

  CHAPTER 33

  SYNTHESIS

  Our observation of nature must be diligent, our reflection profound, and our experiments exact. We rarely see these three means combined, and for this reason, creative geniuses are not common.

  —DENIS DIDEROT, “On the Interpretation of Nature”

  JACOB WAS NOT IN PARIS TO CELEBRATE THE GREAT NEWS OF Ullmann and Erdös’s liberation. He was still in Pasadena with Brenner, and feeling discouraged. After three weeks of experimenting, they had accomplished nothing. It was probably unrealistic to think that two people who had not worked together before could fly to a laboratory six thousand miles away and make a technically complex experiment work in a short period. For Jacob, it was the first time he had ever worked outside of the Pasteur.

  Moreover, few believed in his and Brenner’s idea anyway. Before arriving in Pasadena, Jacob gave a series of seminars along the West Coast. While his work on gene regulation with Monod was well received—including their concepts about repressors, operators, and operons—the idea of an intermediate carrying information from the gene to the ribosome was not. Max Delbrück, who had invited Jacob to Caltech, threw up his hands and said, “I don’t believe it.”

  Neither Brenner nor Jacob was dissuaded, however, from trying their experiment. The idea was to mark or “label” newly synthesized phage RNA with radioactivity, and then to see whether it became associated with already-ex
isting ribosomes. The plan was to exploit Meselson’s unique expertise in labeling molecules in growing cells, and in separating large molecules and complexes in high-speed centrifuges according to their density.

  Nothing went smoothly. They had difficulties getting the bacteria to grow on heavy isotopes of carbon (13C) and nitrogen (15N) that were to mark the ribosomes. The ribosomes also fell apart in the high concentration of cesium chloride in which they were centrifuged. Brenner and Jacob kept modifying the experimental conditions in order to set up for the crucial test, but time was against them. Moreover, Jacob’s war-injured legs were aching in the California heat. It also did not help when Delbrück poked his head into the lab every now and then and asked sarcastically for any news about “X.”

  Their skepticism aside, Brenner and Jacob’s Caltech hosts had made sure that they felt welcome and that they were well fed; they invited them to many parties, lunches, and dinners. But with nothing to show for their efforts, Brenner and Jacob discussed whether they should stay and slog on or return home. They decided they would leave in just a few more days, at the end of June.

  With time running out and little hope left for success, they decided to take a day at the beach. Stretched out on the sand, Jacob and Brenner continued to mull over all of the modifications they had done. Suddenly, Brenner yelled out, “It’s the magnesium! It’s the magnesium!” Brenner realized that magnesium held the ribosomes together and that the very high concentration of cesium chloride, about 8,000 times that of magnesium in the experiment, was displacing the magnesium.

  He and Jacob hurried back to the lab to repeat the experiment with higher levels of magnesium. This would be their last chance. Brenner asked Jacob how much magnesium they should add. He suggested ten times more. Brenner said, “All right,” but he suggested they also try one tube with one hundred times more: “Put in a lot; can do no harm.”

  They were rushing to get the experiment started and to get the very long centrifuge run going. In his haste, Jacob missed a tube with his pipette and spilled a large amount of radioactive phosphorus into a water bath. They tried to rinse the bath out, but it was still radioactive, so they crept down into the building’s basement and stashed the contaminated equipment behind a Coca-Cola machine.

  Then yet another problem arose. In the middle of its long run, the centrifuge broke down. In order to salvage the experiment, they had to move the heavy centrifuge rotor that held the tubes with their experimental samples to another centrifuge. The risk in doing so was that the process for separating the ribosomes and RNA in the centrifuge had to be done in a cold environment. If the rotor and samples warmed up, the experiment, their last chance, would be ruined. Brenner managed to swiftly and carefully carry the rotor down to another cold room and place it into another centrifuge.

  At the end of the run, he had to reverse his steps and bring the rotor back again to the lab. The sample had been separated into layers like a liquid parfait. If Brenner shook or bumped the tubes, he could wreck the separation. He carried the rotor through the halls like it was a holy relic.

  Nervously but skillfully, Brenner then punctured the bottom of the tubes so that each drop from the bottom to the top of the tube could be collected and measured for radioactivity in a Geiger counter. If the experiment worked and Brenner and Jacob were right, the radioactive RNA would be associated with the heavier, preexisting ribosomes and not the lighter ribosomes. They watched the samples get counted one by one. In the first tube with extra magnesium, they saw the radioactive counts rise in the drops containing the heavy ribosomes, and then fall with the light ribosomes. They both shouted and then danced a double jig.

  They had their first evidence that an RNA intermediate carried information from the genes in DNA to the ribosomes.

  Their California gamble had paid off, and just in time. Crick’s black box was now open.

  Jacob flew back to Paris two days later.

  MASTERPIECE

  Monod was not in Paris to congratulate Jacob on his triumph. He was in Cannes for a month’s vacation, but only after having taken care of arrangements for Ullmann and Erdös. Monod saw to it that the two escapees, who had arrived without immigration papers, money, or a place to live, would have what they needed.

  His task of obtaining French visas for them was made considerably easier by his brother Philo’s position within the Ministry of Foreign Affairs. As soon as Ullmann and Erdös safely reached Austria, Monod asked Philo to arrange for their visas, which he did. Philo was about to take up a post as the French ambassador to Australia, so he generously offered his Paris apartment to the couple for a year.

  As for money to live on, some of the funds Monod had raised had been set aside for the two escapees once they made it to freedom. It was enough to support them in Austria while their immigration papers were pending and for a few months after they settled in Paris.

  AFTER WAITING FOR their visas, the two stowaways finally arrived at the Gare de l’Est in Paris on Wednesday, August 10, almost two months after their escape. Madeleine Brunerie met them at the station and took them to breakfast at a nearby café. Erdös savored the taste of what he would thereafter refer to as his “croissant of liberty.” The next day, Ullmann and Erdös went to the Pasteur for a celebratory lunch with Monod, now returned from vacation.

  Of course, the two scientists would eventually need jobs. Monod once again sprang into action, writing colleagues both near and far. Monod soon obtained a fellowship from the Rockefeller Foundation for Ullmann to work at the Pasteur. Erdös secured a position at a research institute just outside of Paris.

  With the Hungarian operation settled, and Jacob back from his California adventure with Sydney Brenner, Monod and Jacob turned again to their collaboration.

  In three years, they had made astonishing progress. Jacob’s inkling of a connection between the induction of bacteriophage and the induction of enzyme synthesis had led to concrete experimental evidence for repressors, operators, operons, and a general model for the logic of gene regulation. And now, thanks to Brenner’s ingenuity, there was evidence for a new entity—Jacob’s “X” RNA—that carried the information for making proteins from the gene to the ribosome.

  But the progress had been in some ways perhaps too swift, as the scientific community had not yet assimilated what Monod and Jacob had discovered and proposed. Since the first PaJaMa paper with Pardee, a succession of papers had appeared every few months that tested a recent prediction, coined a new entity, and made new predictions that were already being tested in the lab before the ink was dry. Given that several key papers were in French, it was understandable that even some privileged insiders had not yet been convinced of or seen the full implications of their work, let alone biologists in general. Indeed, the new experiments with Brenner were not yet written up for publication and would not be until the following year.

  Monod and Jacob decided that they should attempt to write one comprehensive article, in English, that would distill all of their data, integrate all of their ideas, place them into historical context, and explore their broader implications.

  It meant that a lot of time would be spent at Monod’s blackboard, hashing over what they would say and who would write which parts. The challenge was to forge one coherent story from all of the parts of their work, with the dual goal of persuading others of their ideas and catalyzing new research.

  Monod had much more practice at such persuasion. He had succeeded earlier in recasting enzymatic adaptation as a matter of the induction of enzyme synthesis. He had triumphed in the Lysenko debate. Thanks to his mastery of the language, Monod was confident, even stylish, when writing in English. Jacob thought his own English was stiff and awkward. He felt overmatched. The challenge of writing in English and the vast scope of the article meant it would take months to complete.

  That was all right, for both men sensed that the stakes were high, and perhaps growing higher. Madeleine Brunerie, who would type the whole manuscript, knew that as well. A year earlier, i
n October 1959, Mel Cohn had written to her in secret, asking her for Monod’s curriculum vitae and for reprints of his papers. At first he told her the documents were to support his nomination of Monod for a scientific prize to be shared with André Lwoff. Madeleine was suspicious and pressed Cohn as to whether the documents concerned the Nobel Prize. Knowing their shared admiration for Monod, Cohn confirmed her hunch and pledged her to secrecy.

  Madeleine told no one about their pact and waited hopefully for the announcement of the Prizes. A year later, on the day the Prizes were to be announced, she was in Monod’s office taking dictation when the phone rang. It was a journalist asking about two immunologists who had won the 1960 Prize.

  The next morning, Monod asked Madeleine to draft letters of congratulations to the two scientists. Then he asked her, “Do you know, Madeleine, who were two other candidates for the Nobel?” In a low voice, he added, “They were Monsieur Lwoff and me.”

  “I knew that.” Madeleine smiled.

  Monod seemed startled.

  “I have known that for ten months,” she said.

  “Who told you?” Monod asked.

  For once she had the upper hand on “Le Patron.” Madeleine was enjoying the game. She replied, “Excuse me, monsieur, but I don’t believe that I am allowed to tell you.”

  Then Madeleine turned the tables and asked Monod who told him.

  “Cohn!” Monod said.

  Her boss then mused about the Prize. “It would have given me pleasure, sure enough: I could have bought a boat … It would have been good for public opinion. But there are also disadvantages to those who are awarded it.”

  Monod explained that the Prize generated rivalries among scientists. He also feared, like his late friend Camus, that the Prize would mark the end of his creative career. Monod told Madeleine that he did not think he was finished, nor did he think that he would ever win the Nobel. Madeleine told him she was sure that he would.