Genes, Girls, and Gamow

by James D. Watson

  Cambridge (England): April–May 1953

  IN LONDON, SHEILA Griffiths and I first met in Mayfair at Brown’s Hotel near the Society for Visiting Scientists in Old Burlington Street, where, for 17 shillings and sixpence, I got a bed to sleep on and corn flakes and toast for breakfast. Immediately I told her of our manuscript that would be appearing in Nature the next week and very likely create a big splash. Later, as we dined at the Dover Street Buttery, we had much conversational fun, and the evening went by far too fast. But I already knew of a date two weeks off when Alicia Markova was to dance Giselle at Covent Garden, and I had no difficulty persuading Sheila to join me for the occasion.

  Several days earlier I had put my sister on the boat train to Southampton for her return to the States and to our parents, now living amongst the Indiana sand dunes. Betty had been in Europe for almost two years, from just before my first meeting with Maurice Wilkins. Initially we were easily spotted as Americans, especially me with my closely cropped hair and lumberjack shirts. But Betty had acquired a continental flavor from her Jacques Faith suits and when I spoke I was no longer recognized as an American. To my surprise, I often passed as Irish, possibly reflecting the language of my Gleason grandmother, who lived with my family when I was growing up. This expatriate phase of our lives, however, was soon to end; she would have to stop being called Elizabeth and be Betty again—a necessary transition from the English to the American way.

  Nevertheless Betty looked forward to going home more than I did. In the late summer she would be setting off again, this time to Japan, to marry an American whom she had known at the University of Chicago. Likewise I was to return to the States at summer’s end to take up a postdoctoral position at the California Institute of Technology in Pasadena. Although I loved my Cambridge life, I saw no way of delaying my departure. For almost a year before the double helix was found, my longtime patron, Max Delbrück, had been counting on me to come to Pasadena to help with the students who were working with viruses that infect bacteria—bacteriophages, or phages, for short.

  Before April had ended, Crick and I had dispatched a second paper to Nature to elaborate on the phrase, “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Francis initially had wanted to be much more specific in our April 25 paper, but I argued that we should understate our model’s implication because our paper was to be followed by ones from Rosalind Franklin’s and Maurice Wilkins’s groups, the two having long gone their separate ways. But once our manuscript had gone to Nature, I, too, worried that if we didn’t state our ideas more clearly somebody else would try to poach them and get some of the credit. Francis wrote most of this second manuscript, which we called “Genetical implications of the structure of deoxyribonucleic acid.” We had less than a week to complete it and as soon we had finished the drawings it went off with Sir Leonard Bragg’s imprint to appear in the May 30 issue of Nature.

  All through those spring days, visitors constantly popped in to see the model. Dorothy Hodgkin, England’s best crystallographer, came over from Oxford with her postdoc student Jack Dunitz, as did later the young theoretical chemist Leslie Orgel, then at Magdalen College. Leslie brought along the short and almost-pudgy Sydney Brenner, who had finished his medical degree in South Africa two years earlier. Sydney, then 26, was attached to the lab of the well-known Oxford physical chemist Cyril Hinshelwood, long notorious in genetics circles for his Lamarckian interpretation of bacterial heredity. But in Johannesburg, Sydney had no way of knowing this about Hinshelwood. Later, Hinshelwood was to get the Nobel Prize for Chemistry as well as become President of the Royal Society.

  Upon arriving in Oxford, Sydney quickly came to his senses and chose to do his Ph.D. thesis research on phages, about which his professor knew close to nothing. By the time we met, Sydney knew that his own phage work would not make a noticeable splash but common sense required him to see his experiments through to their unimportant end. Then he could move on to more promising research objectives. Knowing of Francis’s sales pitch about DNA even before he spoke, Sydney quickly retreated out of earshot from the powerful Crick voice, and we began a four-hour-long, non-stop conversation on the possible involvement of ribonucleic acid (RNA) in protein synthesis. Later, when we came back to Francis’s presence, I felt more than itchy. Like everyone else now within range of Francis’s booming enthusiasm, I was becoming allergic to DNA. So I could not help telling others later that I would barely survive another tour of the base pairs. Learning of my possible defection, Francis took me aside and told me I didn’t realize our work’s deep significance.

  So warned, I even more anticipated going down to London to see Giselle at Covent Garden with Sheila Griffiths. My American stipend of almost a thousand pounds let me get very good stall seats for close viewing of Markova, who I had not seen dance before. During the performance we went through a tiny box of Sheila’s chocolates and afterwards sought out more coffee and conversation before catching our respective trains back to Putney and Cambridge. Then I learned that she had asked a friend to get for her the April Nature issue that she believed contained our article. But she wondered why it made no mention of DNA. Embarrassingly, I realized that she had been given the April 18 issue, not the April 25 issue that included our DNA work.

  The previous September, in the midst of a wine-filled lunch above Lake Locarno, the Paris-based geneticist Boris Ephrussi and I, with his Swiss postdoc Urs Leopold, composed a silly note about terminology in bacterial genetics. We wrote it as a spoof of the turgid writings of Joshua Lederberg, justly much famed for his 1946 discovery at Yale University that bacteria genetically recombine. Later we got our Swiss physicist-turned-biologist friend, Jean Weigle, to add his Geneva address, and dispatched the effort to Nature to see if we could trick its editor into publishing it. Initially I was delighted when a postcard from the editor told us that our inane ramblings would be printed. Later, however, I became apprehensive that they would simultaneously appear with the real thing. So I was more than relieved when it came out the week before. Sheila’s tone now expressed doubts whether our April 25 bombshell even existed. Still, she clearly wanted to see me after the trip I was soon to make to Scotland.

  In Edinburgh, I stayed with C. H. Waddington, the postwar Professor of Animal Genetics, who lived in a Roman-style villa that had been built in the early nineteenth century as the city expanded to the south. Talking to Waddington was a bad letdown, since I had long respected him because of his excellent 1939 book on modern genetics that I used as a graduate student at Indiana University. To my surprise, he now seemed indifferent to the double helix, appearing refractory to the idea that DNA’s complementary structure was at the heart of the copying mechanism for genes. Why he was so dense eluded me then. Only later did I realize that Waddington wanted something more important than simple molecules to control the key attributes of living organisms. In contrast, in Glasgow, its Genetics professor Guido Pontecorvo instantly followed my argument. The next day we took a walk towards Loch Lomond so that we could be served alcohol, because, on Sundays, publicans could legally serve drinks only to persons living more than five miles distant.

  After my return to Cambridge, I wore my new blue blazer when Francis and I were photographed for Varsity, the undergraduate paper that came out twice a week during term. A news story was being written about our Cavendish breakthrough and their main photographer, A. C. Barrington-Brown, spent a morning with us. The occasion was inherently jolly, with Francis making sure that our picture-taker not only got our names right but also learned why our two-stranded model would revolutionize biology. Lacking Francis’s English polish, my attempt to look serious next to the base pairs led to several photos marked by silly grimaces on my face. I looked more acceptable when photographed next to Francis at his desk and sent a print to my parents confirming the news that indeed we were onto something more than important.

  (Reprinted from Nature, Vol.
171, p. 701, April 18, 1953)

  Terminology in Bacterial Genetics

  THE increasing complexity of bacterial genetics is illustrated by several recent letters in Nature1. What seems to us a rather chaotic growth in technical vocabulary has followed these experimental developments. This may result not infrequently in prolix and cavil publications, and important investigations may thus become unintelligible to the non-specialist. For example, the terms bacterial ‘transformation’, ‘induction’ and ‘transduction’ have all been used for describing aspects of a single phenomenon, namely, ‘sexual recombination’ in bacteria2. (Even the word ‘infoction’ has found its way into reviews on this subject.) As a solution to this confusing situation, wo would liko to suggest the use of the term ‘inter-bacterial information’ to replace those above. It does not imply necessarily the transfer of material substances, and recognizes the possible future importance of cybernetics at the bactorial level.

  BORIS EPHKUSSI

  ‘Laboratoire de Génétique,

  Université de Paris.

  URS LEOPOLD

  Zurich.

  J. D. WATSON

  Clare Collego,

  Cambridge.

  J. J. WEIGLE

  Institut de Physique, Université de Genève.

  JDW and Guido Pontecorvo in the Alps above Saas Fee (August 1953)

  During those mid-May days of 1953, I repeatedly failed to get through to Sheila Griffiths—her Putney telephone number seemed perpetually engaged. Thinking I might have better luck in London, I tried again unsuccessfully to reach her after I went to see Rosalind Franklin, who by then had moved to J. D. Bernal’s lab at Birkbeck College in Torrington Square. There Rosalind had been calculating the equatorial reflections expected from our model and was finding them not in agreement with her measurements. Conceivably the radius at which we placed the phosphate atoms in our double-helix model was not quite right. Nonetheless, I felt a little nervous on the train back from the Liverpool Street Station—a Watson-Crick folly was sure to be long remembered. Yet could something so perfectly pretty really be wrong? Happily no one of even half authority thought so, and later that week I happily watched John Kendrew’s wife, Elizabeth, making dramatic large sketches of the model.

  My quietly elated spirits were further boosted when I was invited at the last minute to the forthcoming June symposium on viruses at Cold Spring Harbor Laboratory, Long Island, New York. To my delight, Max Delbrück had written to the lab’s director, Milislav Demerec, that I should there present the double helix. So Francis and I spent the last two weeks in May putting together our symposium paper, frequently arguing out the precise language. For the first time we discussed how spontaneous mutations might occur and less successfully I took on the question of how chromosomes paired. In the end, my ideas about crossing-over didn’t gel, and we knocked out this topic from the final manuscript. During our writing, I finally heard from Sheila Griffiths who enclosed the copy of Huxley’s Point Counter Point that I had loaned to her the previous summer. By then she knew that my talk about the double helix was no bluff for she mentioned reading Ritchie Calder’s piece on it in the News Chronicle. But there was no time to see her before I flew to the States.

  By the time the manuscript was finished, Tony Broad, who had come to Cambridge to build our rotating anode X-ray tube, had made the first demonstration model of the double helix. Even in its plastic case it was beautiful! So on June 1, I put it under my arm, went down to London, took the airport bus to Heathrow, and got on a BOAC Constellation. It flew to New York with almost no passengers, for the next day was the Coronation of Elizabeth II. We stopped at both Prestwick and Gander and the overnight flight lasted some 18 hours. In the morning, as we were nearing Long Island, the pilot used the plane’s loudspeakers to say that Edmund Hillary and Sherpa Tenzing Norgay had reached the top of Mt. Everest on May 29.

  1Lederberg, J., and Tatum, E. L., Nature, 158, 558 (1016). Cavalli, L. L., and Heslot, H., Nature, 164, 1058 (1940). Hayes, W., Nature, 169, 118 (1952).

  2Lingegren, C. C., Zlb. Bakt., Abt. II, 92, 40 (1935).

  Cold Spring Harbor: June 1953

  AS THE PLANE approached New York along Long Island’s Atlantic side, I eagerly looked to the north hoping to see the extensive grounds of the Cold Spring Harbor Laboratory. This tiny institution, located at the end of a long and beautiful harbor off Long Island Sound, still had a pastoral aura about it—perfect for chasing ideas at the measured pace that allowed time for afternoon tennis and much uninhibited dinner talk. That it was so intellectually high-powered was not apparent from its physical appearance. At first glance it resembled a deteriorating New England village, strung out along a country lane with many of the buildings dating from the days of a tiny whaling industry that barely thrived before the Civil War.

  My first period at the lab was in 1948 when I accompanied my thesis adviser, Salvador Luria, from Indiana to join the still-small phage group there. The group’s members, for the most part physicists or chemists, then were revolutionizing genetics through their studies on bacteria and their viruses, the phages. Luria, a Jewish refugee from Fascist Italy, was a familiar face at Cold Spring Harbor, having first gone there in June 1941 for an important meeting on genes and chromosomes. When it finished, he stayed on to do phage experiments with his newly acquired theoretical physicist friend, the Protestant German Max Delbrück, who then saw no future in Hitler’s Germany.

  Soon after my arrival, Max, his wife Manny, and their two young children had already wearily settled into their apartment after a night flight from Los Angeles. They had married in 1941. Max, born in 1906, was 12 years Manny’s senior but now they did not look different in age, as Max, who was six feet plus, had retained the slenderness of his youth. Increasingly, during my first Cold Spring Harbor summer, I had wanted to be as much as possible like Max, even to having a wife like Manny, whose Scottish good looks went well with a free-spirited mind that sought out friends with novel backgrounds and viewpoints. Most appealing were her love of the outdoors, the determined way she played a good game of tennis, and her dislike of academic couples who derived no fun from good-natured mischief.

  Cold Spring Harbor Laboratory, Long Island, from the inner harbor

  By that evening, virtually all the world’s key scientists who worked with phages had arrived and after dinner we began talking either in small groups standing in front of Blackford Hall where we ate or sitting around the big wooden tables on the east-facing porch that faced the harbor. The scope of this Cold Spring Harbor symposium was wider than phages, however, and many leading researchers on plant and animal viruses were attending as well. That this 1953 symposium could be so big, with some 270 attendees, reflected Max Delbrück’s influence on the National Foundation for Infantile Paralysis, an organization that then saw the need to support research on bacterial viruses as well as those that infect animals. Moreover, it provided the fellowship monies that supported me at the time the double helix was found.

  Manny Delbrück and JDW at Cold Spring Harbor, June 1953

  Such a large symposium could be held at Cold Spring Harbor only because a new, Scandinavian-style auditorium had been completed a few weeks before. Notwithstanding its hard green seats, this auditorium was a great triumph for the Yugoslav-born Milislav Demerec, who had been the Lab’s director since 1941. Originally a classical plant geneticist, for many years Demerec had been studying the famous fruit fly Drosophila. Now he was moving much of the long-term research at Cold Spring Harbor into the new era of microbial genetics, both through his own work on bacterial heredity as well as by bringing to the Lab from Washington University in St. Louis in 1950 the great talents of the unusually taciturn chemist Alfred Hershey. Only 18 months later, Hershey with his assistant, Martha Chase, did their famous experiment showing that DNA carries the genetic specificity of phages—a discovery that spurred me even more into finding out what DNA looked like in three dimensions.

  Clearly wanting to talk with Al Hershey, and vice versa, w
as the legendary Leo Szilard, who after the war had decided to switch from physics into biology. In the 1920s, Hungarian-born Leo had first done physics in Berlin and later came as a refugee to the States, where, in 1942, he built with Enrico Fermi the first nuclear reactor at the University of Chicago. Afterwards, Szilard’s desire to patent their accomplishments so greatly irritated the military authorities in control of the Manhattan Project, that General Groves attempted to jail him until the atomic bomb had been used successfully. Although Groves was overruled by Secretary of War Henry Stimson, Groves nevertheless made certain that Szilard never later joined the bomb-design group at Los Alamos.

  Politically unsuccessful in his efforts to prevent the U.S. from using atomic bombs in Japan, Leo needed another big objective. So knowing of Max Delbrück’s move into biology, he came to Cold Spring Harbor in the summer of 1947 to take the two-week-long practical course that Max had started two summers previously to attract more scientists into phage work. Invariably dressed in white seersucker suits that had no chance of concealing his portly frame, Leo did much of his thinking during long bathtub hours. Equally long hours he spent eating, whenever possible joined by associates whose brains he could pick.

  The first rows of symposium seats traditionally were occupied by those with the courage to interrupt speakers whose thoughts had gotten out of hand. Max and Leo were so positioned when Demerec opened the meeting by noting the large number of attendees and thanking the sponsors for providing the necessary travel funds. As soon as Demerec had finished, Szilard jumped up to thank Demerec for going to the great trouble of locating the wartime-like powdered eggs that were being served at breakfast (not since the war had such a delicacy been available to accompany the morning papers). In a more serious vein, Delbrück then went on with an overview of the intellectual food that was to sustain us for the next seven days, noting that the program was arranged around the life cycle of a virus, starting from its free state, through its infection, and subsequent multiplication and release from its respective host cell.