Genius in the Shadows

by William Lanouette

  During the full days at the bay-front campus, students attended lectures, then paired off to learn laboratory techniques for growing and experimenting with phage. At night, participants relaxed around the grounds or attended impromptu talks and seminars. There were also occasional beer-and-pizza parties and square dances. Playful skits marked the course’s graduation ceremony.

  At Cold Spring Harbor everyone was informal, dressed for the summer heat and humidity in shorts or bathing trunks and T-shirts. Everyone, that is, except Szilard. Painfully modest all his life and, by age forty-nine, very portly as well, Szilard wore a three-piece cotton suit and tie to meals and to the labs, only doffing his coat to work over the lab benches.

  “Leo, how can you stand it?” asked Frances Racker, Trude’s sister and wife of biochemist Efraim Racker, when she saw Szilard.

  “I am cooler than anybody else,” Szilard insisted. “When you are dressed to sweat, you sweat. And when you sweat, you get cooler. So I am cooler than anybody else.”

  Around the laboratory, Szilard was freer about exposing his ignorance. In fact, he seemed to flaunt it. While many scientists dread making fools of themselves, Szilard enjoyed queries that were so simple even the experts squirmed. “How do you know this is a virus?” he asked at one lecture on replication in phage. “How do you know it replicates?” In this way he not only learned a new field in the most direct way but also challenged his colleagues to rethink their own knowledge and assumptions.12

  Jacques Monod, of the Pasteur Institute in Paris, first saw Szilard at Cold Spring Harbor that summer, remembering him as a “short fat man” in the front row at a seminar. “He seemed to be sound asleep most of the time and, with his round face and potbelly, he certainly expressed little interest and no aggression. Yet, from time to time he would suddenly wake up, his eyes shining with intelligence and wit, to ask sharp, incisive, unexpected questions, which he would impatiently repeat when the answer did not immediately come straight and clear.” When introduced, Szilard “started shooting question after question at me.” Monod remembered. “Many of the questions seemed very unusual, startling, almost incongruous. I was not sure I understood them all, especially since he insisted on redefining the basic problems in his own terms, rather than mine.”13

  One June evening Szilard sat with Novick on the steps of a lab building and asked Monod about a finding in his doctoral dissertation: When bacteria were given a mix of glucose (a simple sugar) and lactose (milk sugar), they consumed the glucose completely before using the lactose. Monod realized that glucose blocks the consumption of lactose. But Szilard proposed, “Feed both glucose at a lower concentration with the lactose and the two sugars might be consumed simultaneously.” He added that one might be able to achieve that result if the two sugars were fed to the bacteria in a continuous flow system, anticipating that as the glucose is consumed preferentially, its concentration would fall to a level that would allow simultaneous consumption of the lactose. This conversation led Szilard subsequently to conceive, design, and build a continuous-flow system he called a chemostat and apparently led Monod to build an equivalent system he called a biogen.14

  Szilard’s bench mate for the phage course was Philip Morrison from Cornell (who was later at the Massachusetts Institute of Technology), a physicist Szilard first knew at the Met Lab in 1942. Morrison’s hand and concentration were much steadier, and although Szilard tried all the laboratory techniques, he was clumsy and impatient with procedures once the outcome was apparent. He soon realized—as he had in nuclear research— that thinking up experiments is far more fun than actually conducting them and, in the end, let Morrison perform most of their work. Once Szilard saw the point of an experiment and his mind began to wander, he sauntered outside to settle on the lawn and think.15

  More eagerly than most, Szilard tried to extract universal laws from the welter of laboratory results. Like Schrödinger, Szilard was used to making hypotheses about the laws of nature to account for experimental results and contributed to molecular biology as a theoretical physicist. Szilard’s transition was especially easy: He simply continued a habit of thought from childhood and boldly asked about anything that came to mind. “Usually Szilard listened to people only as long as they had something to say that interested him and made sense,” Novick has said. “This meant that he sometimes turned away in the middle of a conversation. He did not waste time with unnecessary social niceties, which is why some people disapproved of him.”16

  In biology Szilard was “a cross-pollinator of ideas and an effective critic of others’ work, an intellectual and ethical inspiration to younger scientists,” the science writer Horace Freeland Judson noted.17 The French molecular biologist François Jacob, who would share with Monod and André Lwoff a 1965 Nobel Prize for work inspired in part by Szilard, called him an “intellectual bumblebee” who carried ideas from place to place.18 Crossing the Chicago campus with Novick one day, Szilard was stopped by a man who thanked him earnestly for a research idea he had suggested. “It worked very well,” he said.

  “Who was that, and what was the idea?” Novick wondered.

  “I have no idea,” said Szilard, shaking his head and smiling as they walked on.19

  Szilard relished molecular biology because he could test ideas almost as soon as he conceived them. “While physics appears to be on the way out, biology does not seem to exist yet,” he said soon after joining the field. “To me it seems quite probable that there must exist universal biological laws, just as there exist, for instance, physical laws [such] as the law of the conservation of energy or the second law of thermodynamics.”20 In physics, experiments often took months or years to design and vast sums of money to set up. More time was needed to analyze the results. But in biology, where physical changes in organisms occur within minutes or hours, a single day’s work could confirm or refute half a dozen hypotheses and inspire a dozen more for tomorrow.

  The appeal of doing so many quick experiments drew Szilard and Novick back to Cold Spring Harbor later in the summer of 1947 and in five subsequent years.21 On that first return, they made “genetic crosses” or matings between differently marked phages to see how the traits of the two parents assorted among the progeny, much as the Austrian botanist Gregor Mendel had done with sweet peas. But when Szilard and Novick tried to continue their work back in Chicago that fall, Novick was unable to qualify for a faculty appointment in biology and instead agreed to survive on whatever research grants they might muster, his income augmented by Szilard’s out-of-pocket supplements. And since Szilard was not technically part of the biology department, he could not use its laboratories and equipment.

  Impatient and clever, Szilard arranged for a laboratory all their own—in a synagogue at an abandoned Jewish orphanage owned by the university. This dingy brick structure, at Sixty-second Street and Drexel Avenue, stood several blocks south of the main campus, in the shadow of the rattling Sixty-third Street elevated-train line. Szilard and Novick took over a twenty-by-thirty-foot basement room cluttered with overhead pipes, and there created a laboratory. They scavenged for furniture discarded by other university labs, and at Sears, Roebuck bought kitchen cabinets, to serve as lab benches, and a dishwasher for their glassware. Newsweek called their setup “one of the weirdest of the radiobiology laboratories,” but Szilard and Novick were grateful for a place to test their many ideas.22

  Szilard’s best ideas came to him as he soaked in his bathtub at the Quadrangle Club, free from all distraction. He emerged dripping wet each morning to scribble notes on a yellow legal pad, a routine that became famous in academic circles.23 When British biologist Julian Huxley visited the University of Chicago in 1959, he happened to stay in a room at the club once occupied by Szilard. “He was tickled to use the tub where Szilard got his ideas,” biophysicist John Platt later recalled. “Like Archimedes,” Huxley said, and told the story over and over.24

  Once dressed, Szilard walked downstairs to read the newspapers over a relaxed breakfast in the club�
��s sunny dining room and at ten or so walked through campus, crossed the grassy Midway, and strolled in to greet Novick each day with the same question: “Any thoughts?” To Szilard, thoughts had power and reality all their own, and he was just as eager to hear where Novick’s mind had wandered—awake and dreaming—as he was to spout his own fresh ideas.

  On sunny days, Szilard dreamed up ideas by the tennis courts behind the Quadrangle Club, where he slumped in a chair, closed his eyes, and wondered about everything from understanding RNA to cracking the tax code. Some mild afternoons he sauntered a dozen blocks through the quiet Hyde Park neighborhood to a white frame house near Fiftieth Street and Kimbark Avenue, the home of law school professor Edward Levi (later chancellor of the university and US attorney general in the Ford administration). With few words, Szilard greeted Levi’s wife, Kate, walked through the house, took a straight-backed wooden chair from the kitchen, and lugged it onto the small back lawn. There he sat under an elm. Sat and thought. And thought. Once in a while he scribbled a note. More often, he simply let his mind wander, opening and closing his eyes as he seized ideas and wrung from them every consequence and conclusion he could find. As the sunlight faded, Szilard returned the chair to the kitchen, thanked Mrs. Levi, and walked back to the club for dinner.25

  One of the first experiments Szilard and Novick undertook was to clarify a difference of opinion between Delbrück and Luria, on the one hand, and geneticist Joshua Lederberg, on the other. Lederberg’s experiments had led him to conclude that mating, or “genetic recombination,” occurred in bacteria. Szilard and Novick designed what they considered to be a decisive test and sided with Lederberg. “I’ll eat my hat if this isn’t genetic recombination,” Szilard wrote to Delbrück and Luria when describing their results. Luria agreed with Szilard, but Delbrück urged them to do more work. When they learned that Lederberg had already made an equivalent test, and discovered his results in a table listing several experiments, Szilard and Novick dropped this work and turned to a puzzling paradox that Delbrück had reported at the 1947 Cold Spring Harbor course.

  Paradoxes fascinated Szilard because he considered them clues to defects in our understanding of the world, and this one led Szilard and Novick to discover a new phenomenon that came to be called phenotypic mixing. They found that if they infect bacteria with closely related viruses, such as the common T2 and T4 strains, some T2 viruses acquire the appearance (phenotype) of T4 viruses, but they remain genetically (in genotype) T2 and subsequently yield only T2 progeny. While in the anomalous stage, T2 viruses behave as if they were T4, in that they can infect bacteria normally resistant to T2, but their progeny cannot.26

  Still intrigued with Monod’s finding that bacteria choose which sugars they metabolize, Szilard speculated about this process in 1948 as he headed west for a vacation with Trude Weiss at the Stead Ranch in Estes Park, Colorado. Unlike most people, Szilard used his mountain vacations not to escape work but to pursue his thoughts even harder. “A mild anoxia” from the thin air, Szilard thought, made him dizzy with fresh ideas, which he caught like butterflies and scribbled on notepads wherever he happened to be.27 “While he worked, he could not be disturbed at all,” an acquaintance who met him in Estes Park recalled.28

  From the Rockies, Szilard visited the Hopkins Marine Station at Pacific Grove, on California’s Monterey Peninsula, where he joined Novick for a microbiology course given each summer by Stanford microbiologist Cornelius B. Van Niel. In letters to Trude in New York, Szilard raved about the “splendid sun” and the “good lectures.” At first, botching went well as he sat on the rocks by the lab, watching sea lions splash as gulls yelped and circled the vacant canneries nearby.29 Between the biology lectures, he scribbled drafts of a paper about international currency reform and proudly passed around manuscripts of two recently concocted satires: “The Diary of Dr. Davis,” about negotiating with Stalin for nuclear disarmament; and “The Mark Gable Foundation,” about ingenious ways to finance science—and to preserve people cryogenically.30

  At Van Niel’s lab that summer, Szilard made a very different discovery. “Unfortunately,” he wrote Trude near the end of his stay, “I have very much fallen in love with the Pacific Ocean, and I do not want to go back to Chicago at all. I do not want to stay in Chicago much longer.”31 Szilard delayed his return by calling on friends at Cal Tech in Pasadena. In Los Angeles he boarded the El Capitan, a luxury express train for Chicago, but climbed off a few hours later at Santa Fe, New Mexico, and checked into Rancho Del Monte, a small hotel in the hills nearby. From there he took walks, read books about enzymes and biochemistry, and studied immunology and tissue culture.

  Not always content when alone with his thoughts, Szilard interrupted botching to telephone his friend Edward Teller, nearby at Los Alamos with his family for the summer, but found he had already returned to Chicago. In a Santa Fe barbershop for a shave one morning, Szilard met by chance University of Chicago economist Rexford Tugwell, and this encounter led to a day together bouncing in a jeep through nearby canyons. With a balcony of his own in the adobe-style Rancho, Szilard daydreamed, wrote, and read in peace. But, ever the urbanite, he grew uneasy from “too few people for maximum privacy” and after a week boarded the train for Colorado.32

  At the Stanley Hotel in Estes Park, Szilard met Novick and on the broad veranda explained the results of his thinking. All summer Szilard had wondered about growing a continuous culture of bacteria. Answering Monod’s glucose-lactose question was one reason to devise such a contraption. Another was to save time. By the procedures then used, researchers who needed actively growing bacteria for phage experiments had to inoculate a culture and wait for two and a half hours before starting to work. Ideas for experiments came to Szilard so rapidly, so urgently, so fleetingly, that even half an hour’s delay seemed insufferable.

  “In great excitement,” Novick later recalled, Szilard said that a continuous culture device might be made by starting with a vessel in which the bacteria could grow. They would be supplied with nutrient liquid that, when it flowed through the growth vessel, would wash out some of the bacteria. The trick, Szilard said, was simply to match the bacterial growth rate with the vessel’s washout rate.33

  Szilard had worked out the mathematics of the system, which showed that the size of the population of bacteria would be determined by the concentration of the controlling growth factor in the input medium, while the concentration of the controlling growth factor in the growth vessel would be determined by the washout rate and would be independent of the population size. Here was a way to keep a bacterial population growing indefinitely and at a rate set by the experimenter. Since the system would maintain a constant concentration of growth-limiting chemical, Szilard proposed that it be called the chemostat.

  Back in their basement lab, Szilard and Novick tested the chemostat idea by building a simple apparatus with available flasks, tubes, and jars; and when it worked as they had hoped, they applied for money to develop their invention. But the National Institutes of Health (NIH)—on the advice of a consultant—concluded it wouldn’t work and turned them down. “Later,” Novick noted, “the NIH invited Szilard to apply again, but he declined.”34 The chemostat has become a standard tool for research in microbiology, physiology, and ecology, since it provides experimental conditions not otherwise available.

  Szilard is remembered by his colleagues for the chemostat, but more importantly, for seeking the utterly practical—no matter how odd it might seem to others. Instead of warming the growth tube of the chemostat to 98.6 degrees Fahrenheit, Szilard thought it simpler to heat a whole room in his laboratory to that temperature. For the graduate students who conducted experiments wearing summer garb, “it was unbearable,” recalled Stan Zahler, then studying phage with Novick.35 But it worked.

  To make his review of experimental records easier to read, Szilard devised a very utilitarian numbering system for his lab notebooks. It seemed odd, but always allowed him to view two consecutive pages. With conventional
notebook numbering, you make the first right-hand page 1, then turn and number the first left-hand page 2. The second right-hand page is 3, the second left is 4, and so on. Using this method you cannot always see consecutive pages: 2 and 3 are visible side by side, but 1 and 2, or 3 and 4, are not. Szilard solved this problem by starting to number the second right-hand page 1 and the page to its left 2. When he turned the page again, he numbered the right 3, the left 4, and so on. Then, by holding vertical the page he was turning, Szilard could always view the notes of the last or the next page continuously. When using this system, he marked the pages with an “H,” for Hebrew notation.36

  Not all work at their Sixty-second Street lab was so practical, and at times it became cosmic—and comic. One afternoon, as Szilard, Novick, chemist Leslie Orgel, and biophysicist John Platt chatted over coffee, their talk drifted to the IQ of dinosaurs. Then someone wondered, “What’s the IQ of God?”

  “God must be very intelligent, because he’s made all these intricate things, like DNA molecules and professors,” Orgel said.

  “Nonsense!” Novick interrupted. “Very stupid! In the first place, it has taken Him six billion years to do all this. And in the second place, He has done it by the clumsiest possible method, natural selection, just throwing away everything He couldn’t use.”

  Grinning, Szilard cut in. “You forget,” he said, “IQ stands for Intelligence Quotient. It’s a ratio of mental age to geological age. And since God is both infinitely wise and infinitely old, His IQ is the ratio of two infinities, which can be a small finite number.”

  “Like that of a smart Hungarian!” Szilard’s companions chanted.37