Avoid Boring People: Lessons From a Life in Science (10 page)

The week following, Renato and I closed down our Davenport lab, returning our pipettes, test tubes, and water baths to the storeroom for storage until the next summer. Renato's wife and two children were about to arrive by boat from Italy, and soon they would be driving to Bloomington. After a much awaited late August lecture by Ernst Mayr on the “species problem,” the summer effectively came to an end. Of the summer crowd, only the Delbrücks and myself stayed on, taking our meals in the Carnegie dorm basement dining room, which opened up to serve the unmarried residents living in the rooms above. Max and Manny were in no hurry to be back in Pasadena since its hottest days normally occur in the early fall. I had the lucky excuse of needing to stay in the East until mid-September, when I was to meet Luria in Washington at the annual meeting of the Genetic Society. Earlier in the summer, Luria had greatly raised my morale by asking me to give a brief talk concerning my data on X-ray-killed phages to complement the paper he would be giving on his and Renato's latest data.

On her way back to Chicago from New Haven, my sister came to Cold Spring Harbor to see how I was living. I soon brought her to the Delbrück flat to meet Max and Manny and see how the phage group operated. She quickly sensed the tight knit of our club, where phages were at center stage and there was little sympathy for those scientists who did boring, if not stupid, experiments on other organisms. My hero worship for Max surprised Betty since his directness and self-confidence were antithetical to my parents’ gentle empathy for those who could not make it to the top. She, moreover, was not at all prepared for Manny's free spirit and her obvious attraction to talented men.

The day before I took the train down to Washington, I walked south on the Cold Spring Harbor path bordering the mill ponds with the objective of reaching Oheka, the banker Otto Kahn's grand folly, whose immense chäteau-like outline could be seen from the sand spit. It lay beyond the Cold Spring Harbor railway station, from which a half-mile-long private road led across the grounds of an equally private eighteen-hole golf course to the many-turreted edifice, whose more than one hundred rooms made it the second largest private dwelling in the United States upon its completion in 1917. To enhance the views from its yet-to-be-built windows, Kahn had brought in countless truckloads of sand upon which to set Oheka higher than other buildings on Long Island. His name was once legendary, with the financial power of the Kuhn-Loeb investment house that he ran with Jacob Schiff rivaling that of the House of Morgan. The Duke of Windsor spent a night in his grand home during his visit to America in the early 1920s. For more than twenty-five years, until his death in 1933, Kahn single-handedly covered the deficit of the Metropolitan Opera. But upon his death at the height of the Depression, the grand Oheka could find no master of sufficient means and was effectively abandoned until it was brought into service for war-related research.

Now it was again vacant and unattended when I found an open door to the garden and wandered amid the cracking plaster of its once grand rooms, from whose windows I could make out the distant Connecticut shore. Walking back more slowly so I could munch upon the wild blueberries thriving on the underlying sandy soil, I mused whether Oheka would ever come back to life. Basically I didn't care since its world was one I had no need to enter. In Cold Spring Harbor the world of the gene already had its waterfront country club, admittedly without the eighteen holes of golf. And though we knew no imperious grandes dames to pay us visits, we had our own equivalent in eccentric theoretical physicists now manic about genes as well as atoms. And instead of seeking instructions from the skies, we had Max's beat to follow.

    Remembered Lessons

1. Use first names as soon as possible

From our first meeting, Max Delbrück called me Jim and likewise wanted everyone to call him Max. Among the phage group gathered around him and Salva Luria, no one was given a professorial designation unless in jest or when someone's apparent pomposity needed to be put down. Titles, like neckties, imply differences in rank or age but science moves best when all are treated as equals.

2. Banal thoughts necessarily also
dominate clever minds

I used to frequently position myself at meals near Max Delbrück, hoping to profit from sharp dissections of new experiments or criticisms of badly thought out ideas. On some days, conversation sparkled, particularly when a visitor brought new facts or gossip about friends from his European past. More often, however, Max found it more compelling to discuss a student's new girlfriend or who had beaten whom in tennis that afternoon. I was discovering that most high-powered minds do not daily generate new ideas. Their brains mostly lie idle until the input of one or more new facts stimulates their neurons to resolve the conundrums that stump them.

3. Work on Sundays

A fixed sabbath from experiments does not jibe with the reality of the human brain. It rests effectively only when it does not want to work and is satisfied with what it has done. With few exceptions, the time frame of experiments cannot be predicted, and mental hibernation should not be preassigned to a regular day on the calendar. An unanswered experimental question is bound to remain in your consciousness. Work done on weekends, in fact, can be more fun than that done on weekdays. You would not be there unless your experiments were going well.

4. Exercise exorcises intellectual blahs

Experiments or ideas should drive you forward but never should be counted on to keep you on an even emotional keel. Success is gratifying and failure is not, but failure is a necessary feature of the work: if your experiments work all the time or your ideas never stop coming, you likely are aiming at goals not worth pursuing. To counter the ups and downs in neurotransmitter levels that are a natural part of a career such as science, incorporate plenty of physical exertion to get outside your head regularly. Following Max Delbrück's example, I began running several times daily to and from the sand spit. Tennis, however, was my favorite nonscientific pastime, particularly when a good player gave me a match that made me work. Then I felt good even though I lost most games. The relaxation that comes from strenuous exercise most likely reflects the physical-stress-mediated release of ß-endorphins, the opiate-like human molecules whose expression is evolution's way of ensuring that humans engage in tasks that promote our long-term well-being.

5. Late summer experiments go against human nature

During the euphoria that comes with long June days, both hard work and hard play are possible. A full day of experiments in no way precludes early evening softball or volleyball games. But by early August, darkness creeps up on mealtime and yellow leaves begin to hint that fall is not that far away. So with the outside water temperature still rising to its early September highs, afternoon beach excursions make more sense than experiments easily put off to the next morning. The last weeks of August are usually best suited for vacations to distant places attractive enough that thoughts of science will fade no more than two or three days after arrival. Several-week vacations never hurt if you can afford them. And on beach walks toward the end of your vacation, your brain may even be sufficiently refreshed to mull over potential experiments you can undertake when back on home ground.

5. MANNERS PASSED ON TO AN ASPIRING YOUNG SCIENTIST

U
PON my return to the less intense intellectual atmosphere of IU in the fall of 1948, I began following up Luria's observations from 1941 that phages suspended in simple salt solutions are much more sensitive to inactivation by X-rays than those suspended in nutrient-rich beef broth solutions. Unclear was whether phages indirectly killed by exposure to reactive molecules generated by X-rays striking surrounding water molecules possessed novel properties not found in phages killed by “direct” X-ray hits. Luria's earlier inactivation curves suggested that several indirect hits were required to kill a phage. In contrast, direct killing was long thought to result from a single ionization event.

While enjoying the first experiments of my own devising, I began anticipating the intellectual excitement that was to come from the impending mid-October weekend visit of Leo Szilard. Just turned fifty, Szilard was then a professor of biophysics and sociology at the University of Chicago, and was driven down by his much younger collaborator, Aaron Novick, also a participant in the 1947 Cold Spring Harbor phage course. Leo had recently received a small Rockefeller Foundation grant to support midwestern genetics meetings of his choosing. The barely five-foot-six Szilard invariably wore a tie with his suit, never trying to hide the potbelly that reflected his fondness for food and aversion to exercise.

Born in Budapest in 1898 to prosperous parents, the extraordinarily intelligent Leo became a physicist in Berlin, where he knew Albert Einstein well and taught modern physics between 1925 and 1932 with Erwin Schrödinger. As a Jew, he had the good sense to flee Berlin the month Hitler assumed power. Soon he was in England, where the fast flow of his ideas was not so well suited to the more stately flow of English science. He seldom spent more than a few months in any one location, and so there never seemed to be enough time for his theoretical hunches to be experimentally tested. Moreover, his desire to seek patents for ideas that had commercial application made his English academic hosts think he valued money more than ideas. Here they were 100 percent wrong. It was only thanks to money from his German patents, one with Einstein, that Leo could afford to stay in science.

No one in England, moreover, knew of the personal anguish attending his 1933 revelation in London that a nuclear disintegration releasing more neutrons than it consumed would unleash the great energy of the atom described by Einstein's famous E = me
²
equation. If the technique for creating such fission events were to fall into the hands of the Nazis, allowing them to build atomic bombs, they would have all the power they needed to conquer the world. Secretly Leo assigned his patent to the British Admiralty, revealing it to close friends only after the uranium atom was experimentally split in Berlin in 1939. Until then Leo had incorrectly targeted first beryllium and then indium as elements likely to produce the necessary chain reaction.

Immediately Leo tried to stop his physicist friends outside the Third Reich from publishing more on uranium fission. But that cat was let out of the bag when, against Leo's advice, Frederic Joliot in Paris soon published his findings that uranium-235 fission generates two neutrons, not one. Leo then became obsessed with seeing that the United States moved ahead as fast as possible toward the construction of atomic weapons. It was he who first composed Einstein's famous fall 1939 letter to Franklin Roosevelt and, a year later, co-opted Enrico Fermi, the 1938 Italian Nobel Prize winner, by then a refugee at the Columbia University Physics Department, to work on uranium fission. Two years later, they moved from Columbia to the University of Chicago, where their nuclear reactor first went critical in early December 1942. Judged too independent to be part of any military-led team, Leo, unlike Fermi, was kept from the subsequent bomb-making activities at Los Alamos by General Leslie Groves, then in charge of the Manhattan Project. But as soon as the first bombs went off, Leo worked incessantly to see that civilians—not the military—were in control of the Atomic Energy Commission.

Now Leo had set his sights on cracking the genetic basis of life. After taking the 1947 phage course, he saw the need for frequent assemblies of bright people to inform him of new facts to chew on. That Bloomington weekend, however, provided no take-home lesson, either from my brief presentation on X-ray-killed phages or from Renato's much more sophisticated experiments on UV-inactivated phages. The most important new results presented, in fact, came from Szilard and Novick themselves. Over the past six months they had become convinced that despite Max Delbrück's very public reservations, Joshua Lederberg's 1946 demonstration of genetic recombination in
E. coli
was correct. Gleefully Leo wrote both Max Delbrück and Salva Luria that he would eat his hat if someone was able to disprove his and Aaron's new experiments. In fact, they were soon to find out that Lederberg had already published similar confirmatory data.

After Szilard and Novick went back to Chicago, Renato returned to experiments where he began seeing irreproducibility, a problem never before encountered in Luria's lab. Agar-coated plates expected to show statistically equivalent numbers of multiplying phages often yielded wildly disparate counts. Then, on a mid-November afternoon, he noticed the agar plates on the top of piles had more phage plaques. Plates lower in the piles, less exposed to the recently installed fluorescent lights, had fewer plaques. This observation was confirmed the next day, telling Renato that visible light reverses much UV damage, an effect soon called photoreactivation. Immediately I tested whether photoreactivation occurred with X-ray-damaged phages but was disappointed to discover only a small, possibly insignificant effect. Salva, then at Yale for a week of lectures, only learned of the light bombshell when Renato and I met him just before Thanksgiving at Szilard's second get-together at the University of Chicago. Immediately Salva feared that his past multiplicity reactivation results might have been badly compromised by inadvertent light exposure. But Renato put his mind at ease, pointing out that Salva already had reproduced multiplicity reactivation under light conditions insufficient for photo-reactivation.

In turn, Salva reminded Renato of a letter from Cold Spring Harbor, from Albert Keiner, which had arrived in Bloomington just before he left for Yale. In it Keiner excitedly told Luria of his discovery early in September that UV-killed bacteria and fungi could be resurrected by visible light. For many preceding months Keiner had also been plagued by ir reproducible results that he thought might be due to variations in the temperatures to which his UV-exposed bacterial cultures were exposed. Just after Dulbecco and I left Cold Spring Harbor, Keiner found that light, not temperature, was the uncontrolled variable messing up his experiments. Luria did not show Kelner's letter to Dulbecco, only casually mentioning the result to him, and Dulbecco made no connection to his own irreproducible results.

We were then all gathered in front of a blackboard in Szilard and Novick's lab, located in the former synagogue of an abandoned Jewish orphanage in a run-down neighborhood adjacent to the University of Chicago. As a physicist, Leo knew that visible light alone was unlikely to furnish sufficient energy to reverse UV damage. But he was intrigued to learn from Renato that visible light had no effect on free phages. It only worked after the damaged phages had entered their host bacteria cells. Immediately Leo began to speculate whether UV-induced mutations would also be reversed by visible light under such circumstances. To answer this question, he and Novick did experiments over the next six months that showed UV-created mutations were “cured” by visible light in the same proportions that visible light reactivated UV-killed bacteria.

Though I was also finding some of my “indirect effect” experiments difficult to reproduce, Chicago was not the place to say so. It was only just before Christmas that I realized that my IU X-rays were producing not only very short-lived free radical molecules but also much more stable peroxide-like intermediates that persisted after the X-ray machine was turned off. Not anticipating this, I had not been controlling the time from X-ray exposure that I did my assays for viable phages. My experiments continued, more confusing than enlightening, until our next Szilard-inspired get-together in Bloomington, just prior to a meeting at Oak Ridge National Laboratory at which Luria and Delbrück were to speak.

Initially Luria had wanted me to make a presentation as well, believing that my results indicated that what had been described as direct X-ray effects were actually caused not by ionizations directly breaking vital phage components but by the effects of reactive chemicals such as free radicals generated by X-rays within the phage particles. Szilard, however, sitting in the front row of our Bloomington gathering, unsentimentally tore that argument apart. He focused on my observation that purified phage particles suspended in nonprotective media lost their ability to kill bacteria every time they were inactivated. All too clearly I saw that I must do more experiments before I ventured again to speak even informally.

My bungled presentation was then followed by a slapstick exchange between Szilard and Novick. Novick was to present their seemingly paradoxical data produced following mixed infection of bacteria by the closely related phages T2 and T4. Sensing that no one followed Novick's argument, Szilard stood up to compound the confusion. Unlike me, however, they truly had something important to say in explaining results that had baffled Delbrück three years earlier. In the end Max had to clarify what they jointly failed to get across. Following mixed infection by T2 and T4, some progeny particles had the T2 genotype but the T4 phenotype, and vice versa. In fact, Leo and Aaron had pulled off some neat science. At the time, Max wrongly thought it elegant but not very important, and he urged Leo and Aaron not to publish their results. Only two years later did they write them up for
Science.

Photoreactivation discussions dominated the Oak Ridge meeting. Albert Keiner talked about results that he had rushed to publish upon learning that Renato Dulbecco also had found photoreactivation. Renato, believing that his discovery had been made effectively independent of Kelner's, initially did not refer to him in a short note later prepared for publication in
Nature.
Upon then reading Dulbecco's proposed phage photoreactivation manuscript, Keiner felt robbed. In his eyes, Dulbecco must have been influenced by his prior work as reported in his letter to Luria. Immediately responding to Kelner's unhappiness, Renato revised his
Nature
note to cite prior knowledge of Kelner's observation.

As soon as I got back to Bloomington, I felt I had to re-convince Luria that I could do meaningful science. So I stopped irradiating impure phage solutions capable of generating peroxides and instead focused on the biological properties of purified phages killed by shortlived free radicals. Soon I had irrefutable evidence that they truly differed from phages killed directly by X-rays. Not only were several damaging events needed to inactivate them, but when so killed, they were incapable of multiplicity reactivation.

By then I was eagerly anticipating going to Caltech for the summer. The phage group would have gone back to Cold Spring Harbor except for Manny's expecting the second Delbrück child in August. Her need to be in Pasadena provided the perfect excuse for a summer in California. Renato's trip, however, was to be one-way since Max had just induced him to move there with the promise of greater intellectual independence and stability than he now had at Indiana. In the meantime, I was finishing up assisting in the bird course, knowing by then where to lead field trips toward the crow-sized pileated woodpecker. Because of its more southerly range I had never been able to see one around Chicago.

The day-and-a-half train trip to California was largely sleepless, and through the train's windows I began to spot magpies and lark buntings as the cornfields gave way to prairie land. I was more than groggy upon my arrival at the Athenaeum, Caltech's faculty club. Its upstairs loggia housed a row of camp-like cots, one of which was to be my cheap berth for the summer. Upon dropping off a rucksack filled with all my possessions, I made the short walk to the Kerckhoff Laboratory, built twenty years before to house biologists brought together by T. H. Morgan, who came to Caltech in 1928. Morgan had been dead now four years, and the new head of the Biology Division, George Beadle, had been brought down from Stanford to bring Caltech into the era of the genetics of microorganisms.

One of Beadle's first moves was to entice Max to move back to Caltech. Beginning late in 1946, he and Manny lived only ten minutes away by foot, in a new one-story ranch-style home they built on one of the few remaining vacant lots near Caltech. When I first went there for supper, I was much impressed by the large main room with a fireplace graced by a large painting done by Jeanne Mammen, a Berlin friend of Max's from the 1930s. Before Hitler's rise to power, she drew and painted the demimonde, but such art would have been degenerate according to Nazi orthodoxy, and the painting now dominating the Delbrück sitting room drew inspiration from Picasso's classical canvases of the 1920s. Much less memorable was Manny's food. She was not one to pore over cookbooks while Max was back at the lab for seminars. Mexican-spiced ground meat and lots of avocados satisfied her and Max, eating being more a practical necessity than a pleasure for them. They cared more about quality in conversation, chamber music, and tennis partners, and were thrilled by the smells and sights of the California outdoors.

Salva would not be arriving for another two weeks, and I wanted to greet him with new experiments on phages killed by hydrogen peroxide. Studying it in Bloomington was never high on the agenda Luria had set for me; my few such experiments were done virtually by stealth. Tantalizingly they hinted that peroxide-killed phages had biological properties identical to those inactivated by X-ray-irradiated bacterial lysates. If so, there would be good reason to believe that organic peroxides were the phage-killing molecules present in my irradiated phage lysates. Working then on the lab bench next to me was Günther Stent, already a year in the Delbrück lab, studying how tryptophan influenced the attachment of phage T4 to
E. coli
cells. Also there was the French scientist Elie Wollman, whose Jewish parents, scientists themselves, had perished in the Nazi camps. Wollman never felt at ease with the young German chemist Wolf Weidel, who cohabited with him in their laboratory room. But Günther, though also Jewish, soon became good friends with Wolf, whose Teutonic upbringing made it painful for him to call Max by his first name.