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, Günther 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 associated with Linus Pauling. Late that summer Linus, after virtually bumping into me at the Athenaeum, gave me a big grin. Initially I assumed that Max and Linus must have interacted often, since when Max first arrived he and Linus coauthored a short note to 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.
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 Günther 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 reassured 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 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, Günther 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 Günther 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, Günther 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 passed 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 assaulted by spines from the prickly pears that, along with the goats, were the island's principal inhabitants. In town, I anticipated 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 Günther and Wolf above the cliffs in his Jeep. Returning empty-handed to town, we soon happily spotted Günther 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 glasses. Günther 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 anticipation 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 participant 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 institute and the intellectual tradition that had spawned Max's first interest in biology. Happily, Kalckar instantly said he would accept me, and I promptly applied for postdoctoral fellowships that would allow me to move to Copenhagen.
At the same time I was repeating many prev
ious key experiments of my thesis to reassure 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 fellowships. Though the bumpy flight made me awfully airsick, the interview went well and in less than two weeks I was awarded a prestigious two-year Merck fellowship. 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 association 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. 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 anticipating 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 manuscripts for the 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 passed 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 pass 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 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 Institute, 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 Günther 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 Institute for Theoretical Physics, where Günther 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 passed, 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 manuscript to the 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.
Just before I left Copenhagen, there was a small microbial genetics gathering to which came the Italian aristocrat Niccolò Visconti di Modrone, whose keen intelligence I had first witnessed the preceding August at Cold Spring Harbor. Just back in Milan from Caltech, Niccolò 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, Niccolò and I bumped into Ernst Mayr, whom Niccolò also knew from Cold Spring Harbor. After we all visited the ancient Certosa di Pavia, we had supper in the large farmhouse of Nic-colò's equally tall and good-looking brother, just back from China.
At the State Serum Institute in Copenhagen, 1951. Günther 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 assumed 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 assemblies. 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 approach
es 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 Delbrück was coming to Copenhagen for an international poliomyelitis conference. When his ship arrived, Günther, 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. Delbrück was ending his European trip with visits to André Lwoff and Jacques Monod at the Institut 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.
Avoid Boring People: Lessons from a Life in Science Page 9