Genes, Girls, and Gamow

by James D. Watson

  At the Cold Spring Harbor Symposium, June 1953: (from left to right) Max Delbrück, Aaron Novick, Leo Szilard, and JDW

  In the past, Max had ridiculed the idea that viruses could exist within certain cells in a latent proviral form distinct from the vegetative phase. But at last summer’s phage meeting at the Abbaye Royamont north of Paris, Max capitulated to André Lwoff, a French microbiologist, after learning of his definitive experiment done at the Institut Pasteur in Paris. Increasingly by then, I and other younger members of the phage group were realizing that Max’s scientific hunches were frequently dreadful. But once he saw the truth he quickly and gracefully reversed course, as shown by his introductory symposium homage to the intellectually penetrating Lwoff, who that day also sat in one of the front rows. Later Lwoff, who was of Russian-Polish extraction, saw no reason himself to present a paper because that was to be done in part by his younger colleague, François Jacob. The new intellectual heavyweight on the scene, François would sit quietly for hours, then suddenly come to life with questions on what the experiments actually told us.

  I gave my report on the double helix halfway through the meeting. There was almost no reason to talk because most participants had already seen my foot-long demonstration model with the A–T and G–C base pairs colored red and green, respectively. Moreover, before the meeting, Max had distributed copies of the first trio of Nature papers to all participants. So my talk could be very brief. I gave it with my loose shirt overlaying short trousers and tennis shoes unencumbered by laces. Not a trace of Odile Crick’s attempt to make me look English remained and, temporarily, it was as if I had never been to England. In emphasizing Francis’s key role, only the plant virologist Roy Markham, the sole other attendee from Cambridge, knew that I was not exaggerating the Crick intellect nor personality.

  With the double helix so perfectly the answer to the dreams of geneticists, little questioning occurred immediately following my talk. But afterwards Barry Commoner, the Washington University biologist, came up to disagree, not wanting to believe that his DNA dye-binding studies of three years before were hopelessly wide of the mark. Leo Szilard’s concerns were of a different sort—shouldn’t I patent the double helix? But he knew that his proposal would not fly and told me I could only be famous, not rich.

  I found the meeting ending much too soon, with phage friends from the past soon departing home to their wives, but I knew the Delbrück’s were to remain at Cold Spring Harbor for the summer. Even before my arrival I planned to stay on at the Lab for another week before returning to England. Later I decided to extend my visit for a further week when I found out that the ornithologist Ernst Mayr’s 17-year-old daughter Christa would be spending some time in Cold Spring Harbor once she graduated from high school. The Mayrs had spent the previous 10 summers at Cold Spring Harbor, coming out from their base in New York, where Ernst worked at the American Museum of Natural History. Born and educated in Germany, Ernst had arrived in America in 1932 after spending several years collecting birds in the Solomon Islands on a bird expedition sponsored by the British philanthropist Walter Rothschild. Ernst had just been appointed Professor of Zoology at Harvard University and soon he and his family would be relocating to the American Cambridge. Before I went to Europe three years earlier, my eyes used to turn first to Christa’s year-younger blond sister, Susie, adorably pretty since birth. Now, however, it was the more intellectual, 17-year-old, brown-haired Christa that I found myself anticipating.

  Ernst Mayr on Blackford Porch, Cold Spring Harbor Lab, 1950

  By the time Christa had arrived, the summer’s phage course had started, and one of the students was Bathsheba de Rothschild from Paris. She was excited about the ideas that Leo Szilard could bring to biology and was working in a lab at Columbia. Bathsheba was keen on modern dance and a major patroness of Martha Graham, whom she brought out for Sunday lunch on the Blackford porch. In the evenings, I accompanied the Mayrs as they sought their good-natured after-supper excitement. One evening we went into nearby Huntington for a Hollywood movie and, afterwards, joined a communal square dance in a field off Highway 25A. For the first time I was swinging Christa as a full-bodied woman, no longer the gangly child of earlier memories. Not at all shy and calmly confident of her beliefs, she was bubbly excited about being accepted by the academically prestigious Swarthmore College.

  Christa Mayr in Cambridge, Massachusetts, 1954

  The night before my flight back to England, we were again part of a square on the big lawn underneath the Charles Adams–like Carnegie dorm that long had been home for unmarried women working as assistants to the more senior scientists. I no longer felt awkward at our changed relationship. After the dancing ended, Christa and I walked down Bungtown Road to the sandspit where we sat next to each other on the warm beach sand, recalling shared memories from past summers. Increasingly I wanted to touch her but, fearing a negative reaction, avoided even holding her hand as we walked back to the Lab’s center. By then, the sun was just rising and Blackford Hall was starkly beautiful in its 1906 classical Italianate form. With butterflies rumbling through my stomach and not wanting to awaken her parents, we silently bid each other adieu on the Mayrs’ doorstep. Christa then slipped through the door and I went up to my monastically bare Blackford room.

  Neither of us was more than half-awake when three hours later I came to say good-bye to her parents and Susie, and to Max and Manny Delbrück who lived in the next apartment. Soon a train journey would start my journey back to England. Until three weeks before, its fabled Cambridge represented all I wanted from life. Now in love, I knew otherwise.

  Cambridge (England): July–August 1953

  A CROWDED STRATOCRUISER took me back to England and Clare College, where I was to remain only two months before moving to the California Institute of Technology, or Caltech for short. After takeoff I dozed off, coming back to life when we made the fueling stop in Gander. The plane carried Krishna Menon, Nehru’s well-known emissary, who was shuttling back to Delhi from a stint at the United Nations. At Gander he made himself very visible as he walked up and down the long waiting hall looking self-important. Later, when the plane landed in London, Sarah Churchill got off first into a waiting Rolls. Winston, her father, had had a stroke two nights before.

  During my absence, the first newspaper article that reflected an interview with Francis Crick came out. It was in the Sunday Telegraph and reached a large audience. As soon as I saw it, I told Francis we should not help generate more publicity. But he strongly disagreed, seeing no reason why the nature of our triumph should not be distributed widely. To me, discretion demanded that we stay quiet and let history judge us, not our peers—at least not minor Cambridge biochemists. Later, when Francis was asked to give a talk on the BBC, I consented only if it was broadcast exclusively on its overseas services. I was afraid that we might be thought grabby and did not want to stir up more discussion as to whether we had improperly used the King’s College data.

  Christa Mayr was much on my mind, but initially I wanted to see Sheila Griffiths again and wrote her a brief note saying that I was back from the States for a brief visit to complete work on a manuscript about the double helix. With it I enclosed a copy of Microcosmographica Academica, a tiny analysis of how to succeed in Cambridge University politics, written in 1908 by Francis Cornford, then a Professor of Classics. Much of what he wrote still held true, and I thought Sheila would enjoy it, particularly because she would also be hearing about Cambridge from Roy Pryce, a young historian friend whom she met in Rome. She replied quickly, indicating her concern about why I had been so long in contacting her. She had spotted a second News Chronicle story about the double helix and wondered whether it was also big news in the States. The way still seemed open to let us know each other better. But now, caught up with love for the newly grown-up Christa, I prevaricated and the summer was to pass without our meeting.

  Soon I was concentrating on a detailed manuscript for the Proceedings of the Royal Society on how we
arrived at the double helix. This time I did virtually all the writing because Francis was finishing his thesis, soon to be forgotten, on the shape of hemoglobin. As I got near the end, I began to relax. It was the first time I had put together language of the type that Lawrence Bragg, Max Delbrück, and Linus Pauling had mastered so well. After it was ready for Bragg to communicate to the Royal Society, I spent a weekend with Sydney and May Brenner in Oxford. There, indifferent to their young son Jonathan’s wishes, I ate all their chocolates, while urging Sydney to go to Cold Spring Harbor when he was finished at Oxford. May, however, was heavily committed to left-wing causes and did not warm to the idea, reacting strongly against the McCarthyism then rampant on the American scene.

  By then I had received a short chatty letter from Christa in response to one I’d sent her soon after my return. The hope that she might reply had kept me checking daily for a letter in my pigeonhole at the Porter’s Lodge. My first letter from the States, however, came from my sister, Betty, still with our parents preparing for her lengthy flight to Tokyo and marriage to Robert Myers. Before she left Cambridge, Peter Pauling urged her to spend a night in Honolulu where his brother, Linus, Jr., was living, married to the heiress Anita McCormick Rockefeller Oser. To Betty’s delight, this stopover was arranged, and she could see whether Linus, Jr. was also a charming Pauling. A separate letter from my mother told me that Betty’s wedding unfortunately had to occur in Tokyo rather than near Chicago, so our family friends would miss seeing who Betty was marrying. Mother, moreover, feared that Bob Myers might be a Republican and wondered why her daughter was going through a governmental security check. Betty was sure of her choice, though, and I no longer worried that she might marry someone of charm but no consequence.

  For several weeks after my return, I kept open the possibility of submitting the double-helix research for a Cambridge Ph.D. Having two such degrees clearly made no sense except for future conversational gambits. But without the Ph.D. pretense, I would not now be ensconced on the R staircase of Clare College with windows overlooking the giant Atlas cedar inside Memorial Court. Although much of the thesis could consist of published material, I would have to write a proper introduction that with perseverance should only take up two or three weeks. By midsummer, however, I saw myself running out of time and semi-reluctantly abandoned thought of the splendid red academic robe worn by holders of Cambridge Ph.D.’s. I equally saw that it made no sense to pursue a research fellowship at Clare. Michael Stoker, its medical tutor, thought that, given the double helix, I would most certainly be awarded one if I applied. But despite its exquisite architecture and perfect garden, I sensed that Clare was unlikely to provide me with a viable social life.

  At our lunches in the Eagle, the nearby pub on Bene’t Street where we invariably had lunch, Francis and I increasingly batted about how the genetic information encoded by the sequence of base pairs in DNA might be used to determine the order of the different amino acids in proteins. Here the DNA base pairs could not directly provide template surfaces attracting specific amino acids because clean experiments had shown that amino acids assemble into proteins in the cytoplasm, totally segregated by nuclear membranes from the chromosomally located DNA. For over a year I had been telling Francis that the genetic information of DNA chains must first be copied into that of complementary RNA molecules. These then must move to the cell’s cytoplasm to function as the templates ordering the amino acids in proteins.

  But until we found the base pairs, I had no idea at the molecular level about how the genetic information of DNA could be passed into RNA molecules. Now the answer was obvious. The same base-pairing scheme involved in copying DNA could be used to make single-stranded RNA molecules upon complementary single-stranded DNA molecules. Of course, there was no firm evidence to convince skeptics that this DNARNAprotein scheme actually existed. But if RNA wasn’t the template for protein synthesis, why should there be so much in cells, particularly those involved in extensive protein synthesis, such as liver cells? Most certainly RNA was not there, say, to control the viscosity of cells, which Francis measured for his first two years in Cambridge at the Strangeways Laboratory as his introduction to biology. Cracking the RNA structure was my next main task. With luck, I could quickly work it out once I got to Caltech.

  Even, however, without knowing the RNA structure, we knew that each amino acid must be selected by groups of base pairs. There were far too many amino acids for a one-to-one correspondence. At first glance, the number of known amino acids was more than 25 whereas there are only four bases in the DNA alphabet. But most proteins have only a smaller subset of amino acids. Oddball amino acids, like the hydroxyproline of collagen, were best hypothesized as arising by enzymatic-induced chemical modifications occurring after the respective true amino acids were incorporated into proteins. Given this viewpoint, there was solid evidence for only 20 genetically specified amino acids.

  We put this list of 20 amino acids to paper after the unexpected receipt of a zany communication from the celebrated, Russian-born, theoretical physicist George Gamow. While temporarily at the University of California, Berkeley, he was alerted to our second Nature paper by his physicist friend, Walter Alvarez. It was not, however, until Gamow had moved on to the University of Michigan that he found time to read it. Writing from the Michigan Union at Ann Arbor in July, Gamow correctly saw that the deep challenge ahead was how genetic information carried by the sequences of DNA bases was used to specify, say, that a cat grows up to be a cat and not a mouse. Most importantly, he saw that the language of DNA used as its letters the four bases A, G, C, and T. Intrigued that a number-theory approach might help solve how genes work, Gamow wanted to see Francis and me during his forthcoming mid-September visit to England. His hand-printed letter, however, had so many whimsical qualities that we did not know how serious he might be. As we both were to have left Cambridge by the time of his proposed visit, I filed his letter away unanswered, never suspecting that we would soon see him face to face.

  At the Institute for Theoretical Physics, Copenhagen, 1930. In the front

  row from the left) are Niels Bohr, Werner Heisenberg, Wolfgang Pauli,

  George Gamow, and Lev Landau.

  By then we were looking forward to a meeting on proteins at Caltech that Linus Pauling (Sr.) had arranged for mid-September. I was going there anyway, but for Francis this invitation was a welcomed acceptance into the real world. Max Perutz, John Kendrew, his student Hugh Huxley as well as everyone important in protein crystallography would be there. Lawrence Bragg was invited in a special way. A letter came from Pauling asking him to be an Honorary Visiting Professor at Caltech and after the meeting to give some lectures on his work. When learning of this the chemist Jerry Donohoe, earlier of Linus’s lab, Peter Pauling, and I, with John Kendrew’s encouragement, saw a way for Francis’s conversational skills to be used at Caltech. Towards this end we took assorted letters from Linus and assembled phrases to read as if written by him. We were especially pleased with the sentence, “Professor Corey and I want you [that is, Francis] to speak as much as possible during the meeting.” The letter ended with the hope that Francis afterwards would also lecture on his work as a Visiting Professor. Linus was soon coming to Europe to go to a Chemical Congress in Sweden, where Peter was to meet him. So Peter took with him a copy of the made-up letter that he was to type on Congress stationery, affix to it a fake Linus signature, and dispatch it back to Francis.

  The following week Lawrence and Alice Bragg invited me to supper at their new home out on Madingley Road. They were very pleased with their new garden and before dinner, while walking me about, Sir Lawrence was very apologetic about his behavior to Francis, saying it was his worst mistake ever in misjudging great talent. After dinner over coffee, Lady Bragg asked what “punk” meant. They said that young Pauling had been there the week before, and after supper he sat down and said, “I feel punk.” I avoided a clear answer to Alice, suspecting that Peter was lamenting his impending loss of Nina, the Pe
rutzes’ small, pretty, blond au-pair girl soon to go back to Denmark. To say this now in front of Bragg, however, would only compound Bragg’s suspicion that Peter’s mind seldom turned to science. On several past occasions, Sir Lawrence had gotten evasive answers from John Kendrew and Max Perutz as to how young Pauling’s first year of research was going. Both knew that soon Peter had to get more serious or go home. But telling this to Linus during his brief Cambridge visit to concede DNA defeat did not quite seem right. So Bragg hoped that Peter would finally exude seriousness upon coming to his home. But, later, all he could remember from his and Alice’s efforts would be “punk.”

  The next day, after telling Peter I had tried to put punk to rest, I set out for the continent, going through Geneva and Zermatt on my way to the International Congress of Genetics on Lake Como just north of Milan. There, for the five-day meeting I was to be with my co-conspirator on the Nature hoax, Boris Ephrussi, and his American wife, Harriet. When I arrived at a big Bellagio Hotel, I found the Ephrussis talking to Baroness Edmund de Rothschild and her daughter, Bathsheba, just back from the bacterial genetics course at Cold Spring Harbor. Asking me to join them for supper, the Baroness later asked me if I wanted some wine and I naturally said, “yes.” Then I was asked to choose it. So I picked out a 1912 bottle, not knowing much about it. A white wine, it was orangish-yellow, being very old. She asked me how it tasted, but I didn’t know whether it was very good or very bad. Bathsheba was equally lost. So the Baroness, who almost never drank, took a taste and said, “Corky, send it back!” We repeated the charade a second time, and when the third bottle was opened, I said it was all right. They were all the same to me.