Avoid Boring People Part 2

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 sh.o.r.e. 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 Delbruck 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. t.i.tles, like neckties, imply differences in rank or age but science moves best when all are treated as equals.

2. Ba.n.a.l thoughts necessarily also dominate clever minds I used to frequently position myself at meals near Max Delbruck, 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 prea.s.signed 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 Delbruck'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 -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 Pa.s.sED ON TO AN ASPIRING YOUNG SCIENTIST.

UPON 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 antic.i.p.ating 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 partic.i.p.ant 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 Schrodinger. As a Jew, he had the good sense to flee Berlin the month Hitler a.s.sumed 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 = me2 equation. If the technique for creating such fission events were to fall into the hands of the n.a.z.is, allowing them to build atomic bombs, they would have all the power they needed to conquer the world. Secretly Leo a.s.signed 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. equation. If the technique for creating such fission events were to fall into the hands of the n.a.z.is, allowing them to build atomic bombs, they would have all the power they needed to conquer the world. Secretly Leo a.s.signed 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 publis.h.i.+ng 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 n.o.bel 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 a.s.semblies 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 Delbruck's very public reservations, Joshua Lederberg's 1946 demonstration of genetic recombination in E. coli E. coli was correct. Gleefully Leo wrote both Max Delbruck 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. was correct. Gleefully Leo wrote both Max Delbruck 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 bombsh.e.l.l 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 circ.u.mstances. 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 antic.i.p.ating this, I had not been controlling the time from X-ray exposure that I did my a.s.says 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 Delbruck 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 Delbruck 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. 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. Nature. Upon then reading Dulbecco's proposed phage photoreactivation ma.n.u.script, 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 Upon then reading Dulbecco's proposed phage photoreactivation ma.n.u.script, 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 Nature note to cite prior knowledge of Kelner's observation. 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 antic.i.p.ating going to Caltech for the summer. The phage group would have gone back to Cold Spring Harbor except for Manny's expecting the second Delbruck 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 finis.h.i.+ng up a.s.sisting in the bird course, knowing by then where to lead field trips toward the crow-sized pileated woodp.e.c.k.e.r. 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 n.a.z.i orthodoxy, and the painting now dominating the Delbruck sitting room drew inspiration from Pica.s.so's cla.s.sical 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 Gunther Stent, already a year in the Delbruck lab, studying how tryptophan influenced the attachment of phage T4 to E. coli E. coli cells. Also there was the French scientist Elie Wollman, whose Jewish parents, scientists themselves, had perished in the n.a.z.i camps. Wollman never felt at ease with the young German chemist Wolf Weidel, who cohabited with him in their laboratory room. But Gunther, though also Jewish, soon became good friends with Wolf, whose Teutonic upbringing made it painful for him to call Max by his first name. cells. Also there was the French scientist Elie Wollman, whose Jewish parents, scientists themselves, had perished in the n.a.z.i camps. Wollman never felt at ease with the young German chemist Wolf Weidel, who cohabited with him in their laboratory room. But Gunther, though also Jewish, soon became good friends with Wolf, whose Teutonic upbringing made it painful for him to call Max by his first name.

Getting reproducible survival curves took more time than I antic.i.p.ated, and the Lurias arrived before I had results to show Salva. Subsequent nonstop lab orgies, during which I was in the lab long past midnight, alternated with manic weekend car trips instigated by the indefatigable Carleton Gajdusek, who had completed his degree at Harvard Medical School two years before and now was supposedly getting postdoctoral experience in both Max's lab and the chemist John Kirkwood's. My first such camping trip ended when the corrugated road gave out five hours below Ensenada in Baja California. Two weekends later, we embarked on an even more insane nonstop drive to Guaymas on the Gulf of California. There for the first time I saw huge man-of-war birds circling over the harbor. A primitive ferry ride across the Rio Yaqui interrupted our journey onward to Ciudad Obregon, where no-degree temperatures finally persuaded Carleton that you could die from the heat. On subsequent weekends, Carleton's extreme traveling turned toward the much cooler Sierras, where on one occasion the rest of our party reached the summit of Mt. Whitney long after he had gone on and descended into a valley to the west.

Such weekends away kept my morale high long after I'd reached the inescapable conclusion that Pasadena was strictly for retirees. Indeed, the average age of the residents in Caltech's hometown was higher than that of any other American city of note. Even on the Caltech campus it was hard to detect a pulse outside the labs and libraries. Social life was most accurately described as nonexistent. Mindful of this reality, Gunther Stent had moved into a canyon house above Caltech occupied by several European postdocs. In this way, he entered into the orbit of the younger chemists a.s.sociated with Linus Pauling. Late that summer Linus, after virtually b.u.mping into me at the Athenaeum, gave me a big grin. Initially I a.s.sumed that Max and Linus must have interacted often, since when Max first arrived he and Linus coauth.o.r.ed a short note to Science Science attacking the notion that putative like-with-like attractive forces would play a role in copying genetic information. More recently Max had become wary of Pauling's self-aggrandizement, though he always remained alert to reports of what Linus was up to from his postdocs. attacking the notion that putative like-with-like attractive forces would play a role in copying genetic information. More recently Max had become wary of Pauling's self-aggrandizement, though he always remained alert to reports of what Linus was up to from his postdocs.

Of all the phage crowd gathered there, I was most at ease with the Doermanns. The high point of my summer came in late August when, on the Athenaeum courts, I took two tennis sets from Gus. In the evenings we would often go into central Pasadena to a restaurant where we had earlier spotted two striking blondes about my age. They, however, never reappeared, nor did our two-hour-long drive to the Pacific Coast beach next to Caltech's marine station at Corona del Mar prove more fruitful for girl-gazing. But at least by then I had accomplished my summer lab objective of showing that peroxide-treated phages had biological properties identical to those killed by X-ray-irradiated phage lysates.

I was thus prepared to speak several days later before an afternoon phage group meeting presided over by Max. The week before, we had listened to the young physicist Aage Bohr talk about the philosophical implications of quantum uncertainties. Here he was a surrogate for his father, Niels, who first had mesmerized Max in the early 1930s. Besides Max, only Gunther pressed Aage for more precise information about his father's supposed philosophical insights. In my back-row seat, I understood not a word of either Aage's thrust or Max and Gunther's counterarguments. In contrast, my talk about three types of X-ray-killed phages revealed no grand paradoxes, nor was much brainpower needed to understand my conclusions. Remembering acutely my April debacle in front of Szilard, I stuck to facts and was careful not to imply any form of breakthrough for radiation biology- much less toward understanding the gene.

The next day in his office, Max told me not to despair of my unexciting results. Instead I should consider myself lucky not to be in Renato's shoes, forced into an emotionally consuming photoreactivation rat race irrelevant to the much more important question of how genetic information is copied. Now was the time for me to concentrate on learning to do science as opposed to winning an experimental race whose outcome would surely be only marginally significant a decade later. George Beadle also rea.s.sured me that I was not off course. To my surprise, he had popped in to hear my seminar and, soon afterward, invited me to dinner at his modest home nearby. Like Max, he was no longer doing experiments, instead getting his scientific kicks from walking about the Kerchoff labs to see what the younger graduate students and postdocs were up to. Already he was justly famous for work at Stanford using the mold Neurospora Neurospora to find genes coding for metabolic pathway enzymes. At forty-five, he didn't see himself making another such conceptual advance. to find genes coding for metabolic pathway enzymes. At forty-five, he didn't see himself making another such conceptual advance.

On the lookout for girls in Corona del Mar, California In early August the Berkeley bacteriologist Roger Stanier gave a seminar on bacterial metabolism. Roger was still a bachelor, and his presence led to the arrival several days later of the Hopkins Marine Station graduate student Barbara Wright. Failing to attract Roger's notice, she caught the eye of Wolf Weidel, who asked her to join him, Gunther Stent, and a Biology Department secretary for a camping weekend on Catalina Island. After Gunther's date vamoosed in favor of a reconciliation with her husband, I was asked to go along out of pity for my being otherwise condemned to another weekend of Pasadena desolation. All went well until the four of us got off the boat at Avalon, the only town, and learned that camping was forbidden. Believing it a ruse to make us rent hotel rooms, we walked toward the island's opposite side hoping to find there a secluded beach on which to roll out our sleeping bags.

On an increasingly blistering afternoon, we realized too late that only goats had ever walked our path snaking down a cliff face to the ocean several hundred feet below. Neither Gunther nor Wolf initially wanted to seem cowardly in front of Barbara, while I awkwardly declared I was going back alone. But after a few more steps downward, the others agreed to turn back. Then, without warning, Gunther's backpack, momentarily off his shoulders, rolled down the steep incline to the beach below. Faced with the prospect of spending real money to replace the bag and its contents, Gunther and Wolf again inched downward, reaching the ocean some twenty minutes later. Soon, however, they found it impossible to retrace their steps. After an hour pa.s.sed with them out of sight searching for alternative upward paths, Barbara and I saw no option but to go back to town.

It was already dusk as we went back along the route we had taken, our bare legs constantly a.s.saulted by spines from the p.r.i.c.kly pears that, along with the goats, were the island's princ.i.p.al inhabitants. In town, I antic.i.p.ated renting rooms so we could shower. But to save money, Barbara insisted that we go back to just beyond the outskirts, where we found a large vacant field to plop down our sleeping bags. There at dawn we were arrested for camping out on the golf course. Later, back at the police station, by saying we were pelican-seeking biologists, I got the police chief to help mount an apparently futile rescue mission for Gunther and Wolf above the cliffs in his Jeep. Returning empty-handed to town, we soon happily spotted Gunther and Wolf near the boat dock. After sunrise they had found a chimney-like indentation in the cliff face that let them squirm upward until they reached a spot from which they could scramble to safety. They were still shaking, knowing they had put their lives at great risk. By then I had lost my reading gla.s.ses. Gunther was even more annoyed that neither Barbara nor I had spotted the expensive camera he'd left behind in his pursuit of his backpack. And so no pictures of our weekend misadventure survive.

Soon after my early September return to Bloomington, Luria asked me to give a bacteriology seminar in which I talked about Seymour Cohen's experiments at Penn showing that phage-infected bacteria synthesized no bacteria-specific molecules, but instead phage-specific DNA and protein. How to go beyond these neat results of Seymour's was not at all clear. No chemist had yet mastered the basic chemistry of either proteins or of the two nucleic acids DNA and RNA. Even Linus Pauling remained then mostly in the dark. Though with great antic.i.p.ation I went to IU's chemistry auditorium to hear him give the fall Sigma Xi lecture, his talk was about the structure of antibodies as opposed to that of the gene.

I wanted to move on as a postdoc to a lab where I could learn nucleic acid chemistry. But no obvious place suggested itself during a late October evening meal with Salva and Zella. Resolution did not come until just before Christmas, during the second of that fall's Szilard-sponsored Chicago get-togethers. By then Joshua Lederberg was part of our in-group, with his first appearance given over to a four-hour monologue on perplexing bacterial genetic results from his University of Wisconsin lab. To the second gathering also came the biochemist Herman Kalckar, now back in his native Denmark after spending the war years mainly in St. Louis. A partic.i.p.ant in Max's first phage course, Herman professed the desire to use some of his rare, recently synthesized radioactive adenine to study phage replication. So both Max and Salva quickly urged me to move on to Kalckar's lab, located in Copenhagen, not far from Niels Bohr's inst.i.tute and the intellectual tradition that had sp.a.w.ned Max's first interest in biology. Happily, Kalckar instantly said he would accept me, and I promptly applied for postdoctoral fellows.h.i.+ps that would allow me to move to Copenhagen.

At the same time I was repeating many previous key experiments of my thesis to rea.s.sure Salva that its conclusions, though not earth-shattering, were at least solid. This task was over by the end of February, allowing me to complete a first draft for my thesis before I flew to New York in mid-March to be seen by the selection committee for National Research Council postdoctoral fellows.h.i.+ps. Though the b.u.mpy flight made me awfully airsick, the interview went well and in less than two weeks I was awarded a prestigious two-year Merck fellows.h.i.+p. I had expected my coming summer to be spent in Oak Ridge with Gus Doerman, who had recently moved to the big Atomic Energy Commission biology lab there. But in early May, Gus told me his attempt to get me a security clearance had failed: my a.s.sociation with the left-wing Luria made me a risk. In the summer of 1948, a Cold Spring Harbor-sited FBI informant had attended the Wallace-for-president fund-raising corn party in Jones Lab to which virtually all the Cold Spring Harbor community, myself included, not so earnestly went. Max came to my rescue, asking me back to Caltech for June and July before I joined him in Cold Spring Harbor for the August phage meeting. By then, Salva had virtually rewritten my thesis, making my late May thesis exam mainly perfunctory.

Only in my last year at Indiana did I have a real girlfriend. She was a perky, dark-haired fellow graduate student in the Zoology Department, Marion Drasher. In early December, I took her to a local production of J. B. Priestley's play An Inspector Calls. Inspector Calls. Soon I was intensely in love, particularly after Christmas of 1949, when we were in New York City together with several other Bloomington students for the big annual AAAS meeting. At the beginning she was the reluctant one, citing her several years' advantage in age. Our relative roles slowly reversed upon our return to Bloomington, however, with me increasingly resistant to making long-term plans together. I was after all antic.i.p.ating my trip to Copenhagen within six months, and in no sense wanted to be tied down. How to go back to just being friends eluded both of us, and when we parted in June I felt bad about being so emotionally inconsistent. Soon I was intensely in love, particularly after Christmas of 1949, when we were in New York City together with several other Bloomington students for the big annual AAAS meeting. At the beginning she was the reluctant one, citing her several years' advantage in age. Our relative roles slowly reversed upon our return to Bloomington, however, with me increasingly resistant to making long-term plans together. I was after all antic.i.p.ating my trip to Copenhagen within six months, and in no sense wanted to be tied down. How to go back to just being friends eluded both of us, and when we parted in June I felt bad about being so emotionally inconsistent.

Much of my second Caltech interval I spent converting my thesis into the first of two ma.n.u.scripts for the Journal of Bacteriology. Journal of Bacteriology. For a few days, I did experiments with a T5 mutant with a lengthened life cycle, but Max chided me that I was wasting my time in the absence of a defined experimental objective. So instead of hanging around the lab without real purpose, I was more frequently in the library or on the Athenaeum tennis court. For several days I was with George Beadle at Caltech's marine biology station, to which he had gone to collect invertebrate specimens. Then Renato and I climbed Mt. San Jacinto again, going through clouds to reach its treeless top, almost twelve thousand feet above Palm Springs. Several days later, my mood suddenly turned serious with the start of the Korean War. But when I pa.s.sed through Chicago on my way to Cold Spring Harbor, and then by boat to Copenhagen, my draft board offered no objection to my going abroad as long as I kept them informed of my address. For a few days, I did experiments with a T5 mutant with a lengthened life cycle, but Max chided me that I was wasting my time in the absence of a defined experimental objective. So instead of hanging around the lab without real purpose, I was more frequently in the library or on the Athenaeum tennis court. For several days I was with George Beadle at Caltech's marine biology station, to which he had gone to collect invertebrate specimens. Then Renato and I climbed Mt. San Jacinto again, going through clouds to reach its treeless top, almost twelve thousand feet above Palm Springs. Several days later, my mood suddenly turned serious with the start of the Korean War. But when I pa.s.sed through Chicago on my way to Cold Spring Harbor, and then by boat to Copenhagen, my draft board offered no objection to my going abroad as long as I kept them informed of my address.

At the Cold Spring Harbor phage meeting in late August, Salva was at ease about the setback to his multiplicity reactivation theory, no longer believing such experiments held vital clues about phage genes. His morale was again high, thanks to a new observation of the frequency of spontaneous mutants among individual bacteria, which he believed showed that genes duplicated by a process akin to binary fission. In contrast, Max still wanted to pull sense out of multiplicity reactivation curves, interpreting Renato's latest examples to suggest the possibility of two forms of DNA-one genetic, the other non-genetic. If phages were indeed so constructed, this might explain Lloyd Kosloff and Frank Putnam's finding at the University of Chicago that when DNA was tagged by introducing radioactive isotopes, only half the DNA of infecting phage particles is transferred to their progeny particles. Here Seymour Cohen pointed out that these radioactive progeny would only have their label in genetic DNA and would in turn pa.s.s 100 percent of their labeled DNA to second-generation progeny particles.

My mind turned again to potential second-generation experiments as soon as the seasickness-inducing vessel Stockholm Stockholm docked in Copenhagen. There I found Kalckar keen that I focus instead on enzymes that make the nucleoside precursors of DNA. But after a week listening to Herman's almost indecipherable English, I saw that experiments with nucleosides would never get at the essence of DNA. I, however, could not figure out a graceful way to tell Herman that my time was better spent going back to phage experiments. Deciding to say nothing, I was soon cycling each day through the center of Copenhagen to the State Serum Inst.i.tute, where Herman's friend Ole Maaloe was keen to follow up the private phage course given to him by Max at Caltech. docked in Copenhagen. There I found Kalckar keen that I focus instead on enzymes that make the nucleoside precursors of DNA. But after a week listening to Herman's almost indecipherable English, I saw that experiments with nucleosides would never get at the essence of DNA. I, however, could not figure out a graceful way to tell Herman that my time was better spent going back to phage experiments. Deciding to say nothing, I was soon cycling each day through the center of Copenhagen to the State Serum Inst.i.tute, where Herman's friend Ole Maaloe was keen to follow up the private phage course given to him by Max at Caltech.

Long before we began producing second-generation results, Kalckar's marriage suddenly collapsed. No longer enzyme-driven, Herman was obsessing about Barbara Wright, the feminine component of our calamitous camping trip to Catalina Island the year before. Like me, she was a new postdoc in Kalckar's lab, as was Gunther Stent, who'd come from Caltech the month before. Delusionally believing Barbara's Ph.D. thesis had earth-shattering implications, Herman hastily arranged an afternoon get-together at the Inst.i.tute for Theoretical Physics, where Gunther and I listened to her explain her experiments to Niels Bohr. Herman then proudly acted as intermediary between Barbara, his putatively visionary biologist, and Bohr, the inarguably visionary physicist. After an hour pa.s.sed, Bohr politely excused himself.

By winter's end, Ole and I finished our experiments, getting the answer that the first-generation progeny transmitted DNA to their second-generation progeny no better than the parental particles. No evidence suggested the existence of two forms of DNA. Though this was not the answer we had hoped for, Max thought it sufficiently important to submit the resulting ma.n.u.script to the Proceedings of the National Academy. Proceedings of the National Academy. Soon Herman himself felt the need to absent himself from his lab, announcing that he and Barbara would spend April and May at the Zoological Station in Naples. Maintaining the facade that I was still his postdoc, Herman asked me whether I wanted to join him in learning more about the marine biology that Barbara had been raised on. Instantly I accepted, for I had no potentially exciting phage experiment on the horizon. Soon Herman himself felt the need to absent himself from his lab, announcing that he and Barbara would spend April and May at the Zoological Station in Naples. Maintaining the facade that I was still his postdoc, Herman asked me whether I wanted to join him in learning more about the marine biology that Barbara had been raised on. Instantly I accepted, for I had no potentially exciting phage experiment on the horizon.

Just before I left Copenhagen, there was a small microbial genetics gathering to which came the Italian aristocrat Niccol Visconti di Modrone, whose keen intelligence I had first witnessed the preceding August at Cold Spring Harbor. Just back in Milan from Caltech, Niccol said I must stop off in his ancestral city to hear a performance at La Scala. Upon meeting my train from Copenhagen, he noticed that my rucksack held all my belongings, and deduced I was without a dark suit. So he arranged for us to go to the same Weber opera but on different nights. At the genetics department in the nearby small university town of Pavia, Niccol and I b.u.mped into Ernst Mayr, whom Niccol also knew from Cold Spring Harbor. After we all visited the ancient Certosa di Pavia, we had supper in the large farmhouse of Nic-col's equally tall and good-looking brother, just back from China.

At the State Serum Inst.i.tute in Copenhagen, 1951. Gunther Stent is on the far left, Ole Maaloe is third from left, Niels feme is standing, and I am sitting in front of Niels.

I would have considered such acculturation alone ample justification for my spending two months in Italy, but a small, high-level meeting on macromolecular structure in the Zoological Station auditorium provided an even better excuse. Until that mid-May gathering in Naples, I had a.s.sumed no one would soon understand the detailed, three-dimensional structure of DNA at the atomic level. Since genetic information, which was encoded within DNA, varied, each different DNA molecule most likely presented a different structure to solve. But my pessimism, born of chemical naivete, lifted dramatically after a talk by the youngish King's College London physicist Maurice Wilkins. Instead of revealing disorganized DNA molecules, DNA in his X-ray diffraction pictures was yielding patterns consistent with crystalline a.s.semblies. Later he told me that the DNA structure might not be that difficult to solve since it was a polymeric molecule made up from only four different building blocks. If he was right, the essence of the gene would emerge not from the genetic approaches of the phage group but from the methodologies of the X-ray crystallographer.

Despite my obvious excitement at his results, Maurice did not seem to judge me a useful future collaborator. So upon arriving back in Copenhagen, I wrote Salva seeking help in finding another biologically oriented crystallographic lab in which I could learn the basic methodologies of the structural chemist. Salva delivered after a meeting in Ann Arbor at which he met the Cambridge University protein crystallographer John Kendrew. Then just thirty-four, John was seeking an even younger scientist to join him. With Salva having spoken well of my abilities, he agreed to my coming aboard to learn crystallographic methodologies from him and his colleagues at the recently established Medical Research Council (MRC) Unit for the Study of Structure of Biological Systems.

By then I was again studying the transmission of radioactive labels from parental to progeny phages, knowing that early in September Max Delbruck was coming to Copenhagen for an international poliomyelitis conference. When his s.h.i.+p arrived, Gunther, Ole, and I went to the Copenhagen dock to greet Max with a large poster saying "Velkommen Max Mendelian Mater." The congress itself was a routine affair except for dinner at Niels Bohr's home within the Carlsberg Brewery. Its founder had long before arranged that his opulent domicile should always be occupied by Denmark's preeminent citizen. Luckily, I was not seated near Bohr, who was likely to be expressing thoughts that no one around him, Danish or foreign, could understand.

Soon I was in England to meet John Kendrew's coworker Max Perutz, to make preparations for my coming to Cambridge in early October. Though John was still in the States, my meeting with Perutz and his boss, the Cavendish Professor of Physics, Sir Lawrence Bragg, went well and I took that night's train to Edinburgh for a two-day peek at the Scottish Highlands near Oban. In returning by train to London, I was engrossed in Evelyn Waugh's Brideshead Revisited. Brideshead Revisited. Delbruck was ending his European trip with visits to Andre Lwoff and Jacques Monod at the Inst.i.tut Pasteur, and so from London I flew to Paris. There on a Sunday afternoon, after watching Monod nimbly scale the big boulders in the woods at nearby Fontainebleau, I said goodbye to Max as he boarded a plane at Orly Though Max was highly skeptical of my foray into a Pauling-like structural chemistry, he did not choose this occasion to say so. Instead he wished me well and I felt the creeping apprehension of knowing that I would no longer be part of the world in which grace and the fall from it could be comfortably predicted by asking, "What will Max say?" Soon I would be somewhere he did not matter. Delbruck was ending his European trip with visits to Andre Lwoff and Jacques Monod at the Inst.i.tut Pasteur, and so from London I flew to Paris. There on a Sunday afternoon, after watching Monod nimbly scale the big boulders in the woods at nearby Fontainebleau, I said goodbye to Max as he boarded a plane at Orly Though Max was highly skeptical of my foray into a Pauling-like structural chemistry, he did not choose this occasion to say so. Instead he wished me well and I felt the creeping apprehension of knowing that I would no longer be part of the world in which grace and the fall from it could be comfortably predicted by asking, "What will Max say?" Soon I would be somewhere he did not matter.

Max Delbruck arrives in Copenhagen, September 1951. From left: Gunther Stent, Ole Maaloe, Carsten Bresch, and Jim Watson Remembered Lessons 1. Have a big objective that makes you feel special No one within the phage group of 1950 would have denied our air of self-importance or our sense of being a happy few. The disciples of George Beadle and Ed Tatum working with Neurospora Neurospora on gene-enzyme connections never came together with such esprit de corps. Max Delbruck's personality was a big factor. His reverence for deep truths and commitment to sharing them unselfishly was saint-like. But these virtues attend many uninspired minds as well and were never the key to the fervor of his acolytes. Instead it was his great commission that we go to the heart of the gene, in search of its genetic and molecular essences. To obssess over less fundamental goals made no sense to Max. Phages, being virtually naked genes that yielded answers after only a night's sleep, had to be the best biological tools for moving forward fast. Legions of graduate students across biology were pursuing things worth knowing but perhaps not worth devoting one's life to. The quest for such an unrivaled prize of indisputable significance fired in our imaginations a devotion such as religion fires in others', but without the irrationality. on gene-enzyme connections never came together with such esprit de corps. Max Delbruck's personality was a big factor. His reverence for deep truths and commitment to sharing them unselfishly was saint-like. But these virtues attend many uninspired minds as well and were never the key to the fervor of his acolytes. Instead it was his great commission that we go to the heart of the gene, in search of its genetic and molecular essences. To obssess over less fundamental goals made no sense to Max. Phages, being virtually naked genes that yielded answers after only a night's sleep, had to be the best biological tools for moving forward fast. Legions of graduate students across biology were pursuing things worth knowing but perhaps not worth devoting one's life to. The quest for such an unrivaled prize of indisputable significance fired in our imaginations a devotion such as religion fires in others', but without the irrationality.

2. Sit in the front row when a seminar's t.i.tle intrigues you By far the best way to profit from seminars that interest you is to sit in the front row. Not being bored, you do not risk the embarra.s.sment of falling asleep in front of everybody's eyes. If you cannot follow the speaker's train of thought from where you are, you are in a good place to interrupt. Chances are you are not alone in being lost and most everyone in the audience will silently applaud. Your prodding may in fact reveal whether the speaker indeed has a take-home message or has simply deluded himself into believing he does. Waiting until a seminar is over to ask questions is pathologically polite. You will probably forget where you got lost and start questioning results you actually understood.

Now, if you have suspicions that a seminar will bore you but are not sure enough to risk skipping it, sit in the back row. There a dull, glazed expression will not be conspicuous, and if you walk out, your departure may be thought temporary and compelled by the call of nature. Szilard did not follow this advice, habitually sitting in a front row and getting up abruptly in the middle of talks when he'd had too much of too little. Those outside his close circle of friends were relieved when his inherent restlessness made him move on to a potentially more exciting domicile.

3. Irreproducible results can be blessings in disguise A desired result in science is gratifying, but there is no contentment until you have repeated your experiments several times and got the same answer. AI Hershey called such moments of satisfaction "Her-shey heaven." Just the opposite feeling of maddening inferno comes from irreproducible results. Albert Keiner and Renato Dulbecco felt it before they found that visible light can reverse much UV damage. Del-briick, struck by how long this phenomenon remained undiscovered, put it down to fastidiousness. He described what he called "the principle of limited sloppiness." If you are too sloppy, of course you never get reproducible results. But if you are just a little sloppy, you have a good chance of introducing an unsuspected variable and possibly nailing down an important new phenomenon. In contrast, always doing an experiment in precisely the same way limits you to exploring conditions that you already suspect might influence your experimental results. Before the Kelner-Dulbecco observations, no one had cause to suspect that under any conditions visible light could reverse the effects of UV irradiation. Great inspirations are often accidents.

4. Always have an audience for your experiments Before starting an experiment, be sure others are interested in the premise. Mindless minor variations on prior good science will generate yawns in the world beyond your lab. Though such almost repet.i.tive motions are good ways for students to learn lab techniques, they should be seen as exercises and not as real science, with their results publishable only in journals that hotshot scientists never read. Now, trying to break new ground may lead to consequences that seem worse than yawns, and you must be prepared for most of your peers to think you are out of your mind. If, however, you cannot think of at least one and preferably several bright individuals who can take appreciative notice of what you are doing, your tenacity may very well indicate that you are either stupid or crazy.

5. Avoid boring people Social gatherings of even successful academics are no different from gatherings of any professional cohort. The truly interesting are inevitably a small subset of any group. Don't be surprised when arriving at some senior colleague's house for dinner if you feel an unexplainable desire to leave when you learn whom you're seated next to. Routinely reading the New York Times New York Times at breakfast will expose you to many more facts and ideas than you are ever likely to acquire during evenings with individuals who in most instances haven't had to think differently since getting tenure. Unless you have reason to antic.i.p.ate a very good meal or the presence of a fetching face, take care not to accept outright any invitations to senior faculty's homes. Leave open the possibility that a sixteen-hour experiment might keep you from coming. If you later find out that someone you want to meet will be there, make known your sudden availability and come gallantly with a small box of chocolates to enjoy with the coffee. at breakfast will expose you to many more facts and ideas than you are ever likely to acquire during evenings with individuals who in most instances haven't had to think differently since getting tenure. Unless you have reason to antic.i.p.ate a very good meal or the presence of a fetching face, take care not to accept outright any invitations to senior faculty's homes. Leave open the possibility that a sixteen-hour experiment might keep you from coming. If you later find out that someone you want to meet will be there, make known your sudden availability and come gallantly with a small box of chocolates to enjoy with the coffee.

6. Science is highly social In high school there is a domain of facts and ideas in which you can succeed separate from the world of hanging out with your peers. Once you get into science, however, worlds collide, and not only your fun but also your professional success demands you know as much about your peers' personality quirks as you do about their experiments. Gossip is a fact of life also among scientists, and if you are out of the loop of what's new you are working with one hand tied behind your back. The intellectual vitality of the phage group drew not only from its meetings but also from constant visits to one another's labs, often for joint experiments. Particularly at the start of your career, you should seize any chance to see how other labs function and talk about results that might be interpreted in new ways. It's all too natural when young to see one's peers merely as compet.i.tors. Some ofthat is necessary and appropriate, but scientific knowledge is not a zero-sum game: there is always something more to be discovered, and getting to know your colleagues can only help you get a piece of the prize.

7. Leave a research field before it bores you When I decided to abandon the genetic approach of the phage group in favor of learning X-ray crystallography to go after the three-dimensional structure of DNA in Cambridge, I was in no way bored with the work of Max Delbruck and Salva Luria. My last phage experiments in Copenhagen were still very rewarding. By then, however, I was more and more drawn to finding the DNA structure, and meeting Wilkins gave me good reason to believe the phage group, for all its high purpose, was not the way. In science, as in other professions and in personal involvements, individuals too often wait for abject misery before effecting change that makes perfect sense. In fact, there is no good reason ever to be on the downward slope of experience. Avoid it and you'll still be enjoying life when you die.

6. MANNERS NEEDED FOR IMPORTANT SCIENCE.

I ARRIVED ARRIVED in Cambridge in the fall of 1951 sensing a majesty of place and intellectual style unmatched anywhere in the world. Its great university, reflecting almost nine hundred years of English history, first centered itself along the banks of the river Cam, whose modest waters move northeast across East Anglia to the market city of Ely. There its ma.s.sive twelfth-century cathedral had long towered over the vast flat fenland marshes that emptied into the Cam forty miles from the shallow waters of the Wash, over which tidal waters from the North Sea still roar twice daily. It was the draining of the fens over many centuries that created the rich agricultural fields and wealth of the great East Anglia estate owners. Their benefactions in return helped create along the "backs" of the Cam the many elegant student residences, dining halls, and chapels that already many centuries ago marked out Cambridge as a market city of extraordinary grace and beauty. in Cambridge in the fall of 1951 sensing a majesty of place and intellectual style unmatched anywhere in the world. Its great university, reflecting almost nine hundred years of English history, first centered itself along the banks of the river Cam, whose modest waters move northeast across East Anglia to the market city of Ely. There its ma.s.sive twelfth-century cathedral had long towered over the vast flat fenland marshes that emptied into the Cam forty miles from the shallow waters of the Wash, over which tidal waters from the North Sea still roar twice daily. It was the draining of the fens over many centuries that created the rich agricultural fields and wealth of the great East Anglia estate owners. Their benefactions in return helped create along the "backs" of the Cam the many elegant student residences, dining halls, and chapels that already many centuries ago marked out Cambridge as a market city of extraordinary grace and beauty.

For most of its history, Cambridge University was highly decentralized, with the teaching exclusively carried out by its residential colleges, among which Trinity was long the grandest, having enjoyed the matchless patronage of Henry Vili. In a room off the Great Court had lived the young Newton, whose greatest science was done in his twenties and thirties before he went up to London to be master of the mint.

Until the mid-eighteenth century, the primary role of the colleges was to educate clergy for the Church of England, the mission carried out by fellows (dons) who were themselves required to remain unmarried while part of college life. Only in the nineteenth century did scienee become an important part of the Cambridge teaching scene. Charles Darwin's serious excitement about natural history and geology came from his exposure in the early 1830s to these disciplines at Christ's College. Over the next half century, the responsibility for instruction increasingly s.h.i.+fted away from the colleges to newly created academic departments under university control. In 1871, the Duke of Devons.h.i.+re, Henry Cavendish, donated funds for the creation of the Cavendish Laboratory and the appointment as the first Cavendish Professor of James Clerk Maxwell, whose eponymous equations first unified the dynamics of electricity and magnetism. Upon Maxwell's early death at age forty-nine in 1879, the twenty-nine-year-old John William Strutt (Lord Rayleigh), famed for his ideas on optics, became the second Cavendish Professor of Physics. In 1904, he was to win a n.o.bel Prize, as would the next four successors to the chair: J. J. Thomson (1906), Ernest Rutherford (1908), William Lawrence Bragg (1915), and Nevill Mott (1977).

By the start of the twentieth century, Cambridge stood out as one of the world's leading centers for science, of the same rank as the best German universities-Heidelberg, Gottingen, Berlin, and Munich. Over the next fifty years, Cambridge would remain in that rarefied league, but Germany's place would be supplanted by the United States, much strengthened by its absorption of many of the better Jewish scientists forced to flee Hitler. England similarly much benefited from the arrival of some extraordinary Jewish intellectuals. If Max Perutz had not had the good sense to leave Austria in 1936 as a young chemist, there would have then been no reason for my now moving along the Cam.

Though winning the great struggle against Hitler had drained England financially, the country's intellectuals took pleasure in knowing that their country's great victory was much of their own making. Without the physicists who provided radar for British aviators during the Battle of Britain, or the Enigma code breakers of Bletchley Park who successfully pinpointed the German U-boats a.s.saulting the Allies' Atlantic convoys, things might have turned out very differently.

Emboldened by the war to think boldly, the then tiny Medical Research Council (MRC) unit for the Study of Structure of Biological Systems was doing science in the early 1950s that most chemists and biologists thought ahead of its time. Using X-ray crystallography to establish the 3-D structure of proteins was likely to be orders of magnitude more difficult than solving the structures of small molecules such as penicillin. Proteins were daunting objectives, not only because of their size and irregularity but because the sequence of the amino acids along their polypeptide chains was still unknown. This obstacle, however, was soon likely to be overcome. The biochemist Fred Sanger, working less than half a mile away from Max Perutz and John Kendrew at the MRC lab, was far along the path to establish the amino acid sequences of the two insulin polypeptides. Others following in his steps would soon be working out the amino acid sequences of many other proteins.

Polypeptide chains within proteins were then thought to have a mixture of regularly folded helical and ribboned sections intermixed with irregularly arranged blocks of amino acids. Less than a year before, the nature of the putative helical folds was still not settled, with the Cambridge trio of Perutz, Kendrew, and Bragg hoping to find their way by building Tinkertoy-like, 3-D models of helically folded polypeptide chains. Unfortunately, they received a local chemist's bad advice about the conformation of the peptide bond and, in late 1950, published a paper soon shown to be incorrect. Within months they were upstaged by Caltech's Linus Pauling, then widely regarded as the world's best chemist. Through structural studies on dipeptides, Pauling inferred that peptide bonds have strictly planar configurations and, in April 1951, he revealed to much fanfare the stereochemically pleasing a-helix. Though Cambridge was momentarily stunned, Max Perutz quickly responded using a clever crystallographic insight to show that the chemically synthesized polypeptide, polybenzylgluta-mate, took up the a-helical conformation. Again the Cavendish group could view itself as a major player in protein crystallography.

The unit's resident theoretician was by then the physicist Francis Crick, who at thirty-five was two years younger than Max Perutz and one year older than John Kendrew. Francis was of middle-cla.s.s, nonconformist, Midlands background, though his father's long-prosperous shoe factories in Northampton failed during the Great Depression of the 1930s. It was only with the help of a scholars.h.i.+p from Northampton Grammar School that Francis moved to the Mill Hill School in North London, where his father and uncle had gone. There he liked science but never pulled out the grades required for Oxford or Cambridge. Instead he studied physics at University College London, afterward staying on for a Ph.D. financially sponsored by his uncle Arthur, who after Mill Hill had chosen to open an antacid-dispensing pharmacy instead of joining the family shoe business.

Unlike Max and John, who came into science as chemists and now possessed Ph.D.'s, Francis's doctorate was not completed. He had done just two years of thesis research, winning a prize for his experimental apparatus to study the viscosity of water under high pressure and temperature, when the advent of the war moved him to the Admiralty. After joining the high-powered group set up to invent countermea-sures against German magnetic mines, his boss, the Cavendish-trained nuclear physicist Harrie Ma.s.sey, gave him in 1943 the challenge of combating the German navy's latest innovation. In great secrecy, their s.h.i.+pyards had under construction a new cla.s.s of minesweepers (Sperrbrechers) (Sperrbrechers) whose bows were fitted with huge five-hundred-ton electromagnets designed to trigger magnetic mines lying a safe distance ahead. Crick came up with the clever idea that a specially designed insensitive mine would not explode until the whose bows were fitted with huge five-hundred-ton electro