by James Watson
Summer had effectively arrived in Bloomington, with the late May daytime temperatures in Luria's inadequately air-conditioned attic lab often too high for our agar plates to gel quickly. Doing more experiments that term made little sense, even when the temperatures temporarily dipped, and besides, I was preparing for my math finals. I wasn't worried about Advanced Calculus. Graves had let us know that all graduate students would get at least a B for staying in the course (by then all the undergraduates had dropped out). But Differential Equations with Professor Kenneth Williams was another matter. Everyone knew that his real passion had long since become the Civil War and his books on the topic, for which he had received much acclaim. I had no rapport with him, finding him mean-spirited when not boring, and was relieved to get off with a B-.
Max Delbrück with Salvador Luria and his coworker Frank Exner at Cold Spring Harbor symposium, 1941
I was in high spirits when I briefly returned home on my way to Cold Spring Harbor and my first trip to the East Coast. The year had exceeded even my highest hopes, since I was now in the thick of the quest to understand the gene. I became more than aware of the advantages of having attended the University of Chicago, where I had learned the need to be forthright and call crap crap. It was not that I was inherently brighter than my fellow graduate students; I was just much more comfortable challenging ideas and conventional wisdom, whether it concerned politics or science. And never forgetting Robert Hutchins's wisdom that the academic world abounds in triviality, I was ever mindful of what sort of work would further my career and what would be merely idle learning.
Remembered Lessons
1. Choose a young thesis adviser
The older the scientist you choose to do your Ph.D. thesis with, the more likely you will find yourself working in a field that saw its better days a long time ago, possibly before you were born. Even when a mature scientist still has all his marbles, he often wants to put more bricks into an edifice that already has enough rooms. This was most certainly the situation with H. J. Müller when he came to Indiana. Though his lectures had much to offer graduate students, the heyday of research like his had long passed, which meant there were no obvious good job prospects for those now working with him. Young professors in contrast are generally hired not for grandeur but because they represent a new intellectual thrust not present in a department, one with hopes of remaining lively over at least the next decade. Moreover, they are likely to have smaller research groups than more senior professors, around whom funds as well as stodgier minds tend to aggregate. I most certainly profited from being Salva Luria's first Ph.D. student and not having to share his attention with other students. Then just expecting his first child, Luria did not yet have the family man's demands on his time, and so even on weekends he was frequently in his lab office, his work proceeding as fast as humanly possible.
2. Expect young hotshots to have arrogant reputations
Those not in Luria's immediate circle frequently made snide remarks about the air of superiority evinced by the phage group around him and Delbrück. Luria's occasional brusqueness in dismissing a scientific objective as rubbish not worthy of a seminar was bound to unsettle colleagues accustomed to good Hoosier manners, whereby good neighbors didn't judge one another too critically. But no matter how polite, intellectuals who break new ground inevitably threaten minds continuing in old ways. Believing that your way to success holds more potential than past approaches and not saying so is of no service to your students. But outside their devoted coteries, intellectual pioneers are bound to be found arrogant at best, delusional at worst. Use your head and draw your own conclusions.
3. Extend yourself intellectually throughcourses that initially frighten you
All through my undergraduate days, I worried that my limited mathematical talents might keep me from being more than a naturalist. In deciding to go for the gene, whose essence was surely in its molecular properties, there seemed no choice but to tackle my weakness head-on. Not only was math at the heart of virtually all physics, but the forces at work in three-dimensional molecular structures could not be described except with math. Only by taking higher math courses would I develop sufficient comfort to work at the leading edge of my field, even if I never got near the leading edge of math. And so my B's in two genuinely tough math courses were worth far more in confidence capital than any A I would likely have received in a biology course, no matter how demanding. Though I would never use the full extent of analytical methods I had learned, the Poisson distribution analyses needed to do most phage experiments soon became satisfying instead of a source of crippling anxiety.
4. Humility pays off during oral exams
During my second year I faced the usual oral exam to test whether I had sufficient background knowledge in my field before focusing almost exclusively on my thesis research. It was two hours long, precluding too many topics from being broached, and since I knew which professors were on the three-person committee I could reasonably narrow down the questions I might be asked. Even so, orals are one of the occasions in graduate school when they have you by the short hairs: the examiners, if so inclined, could ask just about anything they like. You do best by answering them as you would a police officer who has pulled you over for speeding. If you are prone to cockiness, it is better to affect nervousness, as even mild confidence may inspire some to take you down a peg, forcing you to repeat part of the exam some months later.
5. Avoid advanced courses that waste your time
After my three-person thesis committee was formed, I met with it to discuss advanced technique courses that I might need. Given that I now worked with phages multiplying in bacterial cells, I was in no position to tell the new resident whiz in bacterial physiology, Irwin (Gunny) Gunsalus, that I could get by without learning to measure key bacterial metabolic enzyme reactions. He devised a short lab course for me exclusively, and I got the A customary in such circumstances. But when the genial plant geneticist Ralph Cleland suggested that I follow up his uninspired cytology course with his fall offering on histological methods, I bluntly declared the course a waste of my time. Always polite in the Hoosier way, Cleland looked pained but did not challenge me. Returning with me to his bacteriology lab afterward, Luria let me have it and warned I must never again show contempt to a faculty member. Gunny took my side, making my day, saying that I had shown the kind of intellectual directness ascribed to the young J. Robert Oppenheimer.
6. Don't choose your initial thesis objective
At the time of my first experiments, I was too naive to devise an appropriate first research objective or even to choose wisely among alternatives presented by others. I therefore started my research on a problem that interested Luria. He showed an immediate interest in my results and saw that the control experiments were done. Luria had, moreover, wisely started me off on a problem not crucial to the progress of his own research, and so at no time would I feel pressed for my experiments to keep pace with his agenda. Happily, my first experiments yielded positive answers and Luria was gracious enough not to add his name to the abstract I submitted to the Genetics Society summarizing my first months’ findings. Soon I was deciding my own experimental course and I would change my direction several times over the next two years. The two journal papers that summarized my thesis results would likewise appear under my name only, even though Luria helped me greatly, effectively rewriting many of my sentences before they were shown to other committee members, making the articles much more readable. Despite this needed help, Luria allowed me to feel that the papers belonged to me for better or worse and that I was working on behalf of no one but myself.
7. Keep your intellectual curiosity much broader than your thesis objective
Once a thesis is under way, it can feel like an all-consuming marathon. But my graduate experience was much enhanced by excellent courses I took over most of the time I was working on my thesis. There was always an alternative stimulation when my experiments weren't yielding the desired results.
My favorite courses required long term papers and made me read original papers on topics I never would have delved into otherwise. Particularly influential in my intellectual development was the long paper I wrote at Tracy Sonneborn's suggestion on the German biochemical geneticist Franz Moewus's controversial experiments using the green algae Chlamydomonas. A recent course on scientific German let me read his original papers, including some published during the war and not generally known. Though Moewus's veracity had been challenged on the basis of results that seemed statistically too perfect, Sonneborn was intuitively persuaded by Moewus's elegant demonstrations of how genes control enzymatic reactions. Believing I had found new ways to interpret his data, I, like Sonneborn, also wanted to believe in Moewus's results. Afterward, Tracy incorporated part of my term paper analysis in a long review of Moewus's work, but to our mutual dismay Moewus was found several years later to have faked his data. It was not a pleasant outcome, but if nothing else it was a valuable lesson about the dangers of wishful thinking in research, one better learned poring over someone else's work rather than one's own.
4. MANNERS FOLLOWED BY THE PHAGE GROUP
I REACHED New York City in mid-June 1948 after an overnight ride from Chicago on the Pennsylvania Railroad. At McKim, Mead, and White's Beaux Arts masterpiece Penn Station, I carried my luggage to an adjacent Long Island Railroad platform for the hourlong trip on to Cold Spring Harbor. A taxi whose base was the small wooden train station then brought me to the head of the inner harbor on whose innermost western shores lay Cold Spring Harbor Laboratory. I was let off in front of Blackford Hall, the summer center for the Lab where everyone ate, and whose upstairs dormitory space contained seventeen austere, concrete-sided single rooms. In one of these I was to stay all summer. Downstairs, in addition to the dining room, there was a lounge with a fireplace, a large blackboard, and three imposingly baronial wooden chairs that had been there ever since Blackford's construction in 1906.
Then the laboratory was effectively divided into two parts: a year-round Department of Genetics, supported by the Carnegie Institution of Washington, and the Biological Laboratory, a largely summertime effort under the patronage of the wealthy local estate owners. The latter body organized the summer courses and prestigious June meeting, the Cold Spring Harbor Symposium on Quantitative Biology, as well as providing housing and lab benches for summer visitors such as Luria and Delbrück. In 1941, the Yugoslav-born and Cornell-trained Milislav Demerec, the new director of the Department of Genetics, also took control of the community-supported Biological Laboratory, changing its emphasis from physiology and natural history to the study of the gene, his own interest. During his first year as director, Demerec staged the 1941 Cold Spring Harbor Symposium on Genes and Chromosomes. To this seminal meeting came both Hermann J. Müller and Sewall Wright, as well as Max Delbrück and Salvador Luria, for whom Demerec provided space to work together on phages in the Jones Laboratory.
After America entered World War II later that year, Demerec deployed most Biological Lab space to war-related activities. Jones Laboratory, however, being unheated, remained unoccupied and was thus still available to Delbrück and Luria by the time summer came. There were effectively no other wartime summer visitors except for the German-born ornithologist Ernst Mayr, then based at the American Museum of Natural History in New York City, whose research on evolution was complementary to Demerec's interest in genetics. With the director's natural affinity for European-born scientists, Cold Spring Harbor's atmosphere rapidly changed from that of a Yankee bastion, with a history of research in eugenics and an unmistakable anti-Semitic bias, to an international institution whose vigor much depended on foreign visitors, the matter of whose being in some cases Jewish posed no impediment to either scientific involvement or social acceptance.
Cold Spring Harbor was a place where reasoning through numbers was paramount long before Demerec's rule. In 1930 the biophysicist Hugo Fricke was appointed to the Biological Laboratory's staff, and 1933 saw the first Cold Spring Harbor Symposium on Quantitative Biology, its main purpose being to bring physicists and chemists together with biologists to help decipher the molecular basis of life phenomena. It was in this sense quite natural that physicists such as Delbrück and later Szilard were so warmly welcomed into the Cold Spring Harbor community.
My first afternoon's inspection of the digs and labs for the summer visitors revealed much physical dilapidation, the general atmosphere being that of a run-down summer camp. In fact, some visitors lived in tented cabins sited on the grass behind Blackford Hall, itself centrally heated only many years later. Both Hooper House and Williams House, then used to house summer scientists with families, were built in the 1830s as “tenements” for workers in the antebellum whaling industry. Equally rundown was the three-story Firehouse, whose name dated from its original use as the town's first fire station before the Biological Lab bought it in 1930 for $50 and transported it across the harbor on a barge to provide more summer housing.
Canvas tents behind Blackford Hall sheltered some summering scientists.
The Laboratory towed in the Cold Spring Harbor Firehouse to house summer scientists in 1930.
The research buildings housing the Department of Genetics dated from the first decade of its existence and, while of far sturdier construction, had an unmistakable turn-of-the-century smell. The main laboratory, an Italianate 1904 building, had a library on the first floor with labs on the top floor and in the basement. On two sides it was surrounded by the cornfields of the Brooklyn-raised and Cornell-trained geneticist Barbara McClintock, whom Demerec had recruited in 1941. Before coming to the symposium that June, she had resigned from the University of Missouri, where her sharp, independent mind was not so well appreciated. Demerec, however, with his eye for real talent, soon got Carnegie's permission to offer her a modest salary and second-floor space in the 1912 Animal House. There mice strains predisposed to cancer had been under intensive study since the early 1920s.
Despite the extraordinarily beautiful surrounding harbor and hills, the state of the labs and residences gave first-time visitors the distinct impression that Cold Spring Harbor would not likely long remain a site of high-powered science. But I then had no concern for the state of the buildings as long as they had the facilities needed for my phage experiments. Our IU contingent was to work in the 1927 Colonial Revival-style Nichols Building, which housed the Biological Laboratory's only two scientists, Vernon Bryson and Albert Keiner. Both did experiments on mutagenic agents in bacteria, and we could use their steam sterilizer (autoclave) and oven to prevent unwanted contamination of our bacterial cultures.
Several days later, Luria arrived with his New York-born wife, Zella, a Ph.D. student in psychology whom he'd met soon after arriving at IU. She was expecting their child at the end of the summer and welcomed the prospect of Blackford meals over preparing food in their Williams House apartment, furnished with castoffs from local estate owners. Renato Dulbecco by then also was on hand, having driven east in a secondhand Pontiac that he subsequently would use to take his wife and two young children back to Bloomington after their arrival from Italy. One of its first uses on the East Coast was to drive Max Del-briick and his wife, Manny, to the Marine Terminal at La Guardia Airport, where they boarded a Pan Am flying boat to England. From there they were to go on to Germany, where Max's family had suffered badly in the war, his brother, Justus, dying of diphtheria in a Russian prison camp after earlier being incarcerated by the Nazis.
Tracy M. Sonneborn and Barbara McClintock at Cold Spring Harbor in 1946
Back for their sixth straight summer were Ernst Mayr, his wife, Gretel, and their two almost teenage daughters. He had long been one of my heroes, not only for his ornithological expeditions in the late 1920s to New Guinea and the Solomon Islands, but even more because of his seminal 1942 book, Systematics and the Origin of Species. I had excitedly read it during my last year at the University of Chicago, along with the equally influential Genetics and the Origin of Spec
ies by Theo-dosius Dobzhansky, a professor at Columbia University and frequent visitor to Cold Spring Harbor to see his close friend Demerec.
In our Nichols Lab room, Dulbecco and I soon began daily experiments to see whether UV light and X-rays inactivate phages by causing localized damage to one or more of their genes. Luria had arrived hoping that the phenomenon he observed, called multiplicity reactivation (whereby UV-damaged phage particles could somehow still multiply), was best explained by the independent replication of undamaged genetic determinants. But Renato's experiments soon began to show that the genes surviving a given UV dose replicated more slowly than their unirradiated counterparts. Conceivably there were no independently multiplying sets of phage genes. Instead they might linearly arrange on one or several chromosomes. If so, multiplicity reactivation was the result of crossing-over events between phage chromosomes, with genetic determinants from different particles coming together as a complete set of undamaged phage genes.