Genes, Girls, and Gamow Page 25

  Back in the Cavendish X-ray group, I found John Kendrew, Francis Crick, Ann Cullis, and Don Caspar all enthusiastic about their recent trip to Madrid for an early April symposium featuring the structures of proteins, nucleic acids, and viruses. Rosalind Franklin and her Birkbeck virus group attended, too, as did Maurice Wilkins with his King’s College DNA structure compatriots. Of real surprise to Francis, and even more so to Odile, they found themselves not only tolerating but much liking Rosalind. In company that did not make her nervous, she was fun to have around. Peter Pauling, before his problems crashed in on him, had long planned to be there also. With Julia in the easier middle part of her pregnancy, at the last moment he also made the trip. As newly marrieds, they were living south of the Thames, near the Elephant and Castle Station from which he could take the underground into the Royal Institution where he had already started working.

  At Madrid Crystallographic Meeting, April 1, 1956. From left: Ann Cullis, Francis Crick, Don Caspar, Aaron Klug, Rosalind Franklin, Odile Crick, and John Kendrew

  The prospect of solving the structure of polyadenylic acid, or poly(A), was now excitedly bringing me regularly to the Cavendish X-ray room. As a synthetic polyribonucleotide, I thought it might provide vital clues about RNA’s structure. On my return to Cambridge from Egypt I heard that some highly purified poly(A) had just been made in Roy Markham’s lab, using procedures published by Severo Ochoa’s lab in New York. Using it, I made an oriented fiber and put it in front of our rotating anode X-ray beam. Happily its X-ray diffraction pattern had the smell of a helix. An even better pattern later emerged from a fiber made just before Belinda and I strolled to the nearby Arts Theatre to see a weekday performance of Samuel Beckett’s new play Waiting for Godot. With so little said between its two tramp protagonists, I became bored and restless, eager to get back to the Cavendish basement to see the latest X-ray pattern from this RNA-like molecule containing adenine as the only base. It convincingly told me that poly(A) was also a double helix. Its two chains had their sugar-phosphate backbones on the outside and running in the same direction, each making a complete turn every 31 angstroms. Two hydrogen bonds between pairs of bases held the two chains together with their base-pairing arrangement identical to that earlier found in crystals of adenine hydrochloride. Now that I had poly(A)’s structure right, I could go back to the States with the satisfaction of again doing solid crystallography.

  By then I knew that I would have Alfred Tissières with me at Harvard. His research fellowship at King’s was ending next year, and he saw advantages to closing down his work on biological oxidation to investigate instead how RNA carries the genetic information for protein synthesis. Several years before he had briefly used the ultracentrifuge in Markham’s lab to examine the small RNA-containing cellular particles on which protein synthesis occurs. These particles were the size of the small spherical plant viruses and, like them, might be constructed from large numbers of identical protein subunits. At Harvard, we planned to characterize them in much more detail. That my new lab in the States had to have a primary experimental bent was all too clear. Even Francis was tired of speculation carried on too long before the relevant experimental facts were known. Now Alfred had to decide whether he should take his Bentley across the Atlantic.

  Late in May, I began writing my manuscript for a meeting entitled “The Chemical Basis of Heredity” that was to be held in Baltimore at Johns Hopkins University in mid-June. Francis and I were to give separate talks, he on DNA and I on poly(A). Still owning few possessions or clothes, it would take less than a day to pack my belongings for my return to the States. The Pauling–Corey space-filling atoms, which I had used in vain to find the RNA structure but had just now successfully employed in finding the poly(A) helix, I would give to the unit. There was no good scientific reason to take their heavy bulk on to Harvard.

  Just before I left for Boston, Belinda Bullard and I slipped without tickets into the half-finished May Ball of Clare, my rented black-tie clothes helping me not to look out of place. This year, the May Ball was held in mid-June, the week before the end of the term. Half-alcoholic by the time we sneaked in, the night was just warm enough to stay through to the early morning hours. With time our dancing became increasingly droopy, and we found a bench to sit on and hold hands before the last dance made us get up. This was my first May Ball and it had not ended the way I once wanted—with Christa. But as the dawn broke, I was not unhappy as Belinda and I made our way towards breakfast.

  Baltimore, Cold Spring Harbor, and Cambridge (Mass.): June–September 1956

  UPON MY ARRIVAL at the 10-storey, red-brick, 1920s Baltimore hotel, I discovered that the McCullum Pratt Meeting organizers had assigned Francis and me to a large, presidential-size suite on the top floor. With its elegant French-styled furniture, we had never before been so well treated, and Francis beamed, pointing out that we were getting the recognition that the double helix deserved. The meeting itself was equally first class. Its organizers had assembled speakers and an audience appropriate for the scientific world’s first double-helix-based overview of genetics. George Beadle (“Beets”) was there from Caltech to open the meeting, and he gave a very intelligent overview of what genes are, how they might be replicated, and in what way they direct protein synthesis. Long known for his association with the one-gene, one-protein concept, Beets now spoke of genes as segments along DNA molecules that most likely specified RNA templates for ordering amino acids in proteins.

  Geo Gamow was missed at the meeting as was his genetic-code theorizing. At this moment, he was having fun in San Diego at the space branch of Convair, doing long-range rocketing calculations that included a trip around the Moon. His long-awaited divorce was finally about to happen with the alimony settlement signed and sealed allowing Rho now to be in Reno. Afterwards he went to the Boulder Summer School, from where he later joyously wrote Alex that he had just been asked to join the University of Colorado’s Physics Faculty and was about to go to a “champagne party” that he was giving to celebrate.

  That viral RNA carries genetic information became established fact with this symposium. Heinz Fraenkel-Conrat gave the Berkeley results that confirmed the Tübingen data given in the subsequent discussion by Gerhard Schramm. There were, in addition, two potential bombshells. One was the report by Elliot Volkin and Larry Astrachan from Oak Ridge that the unstable RNA made after phage T2 infection had a base composition very similar to that of T2 DNA. Years later, we realized what they were studying was the very RNA made off DNA templates involved in protein synthesis. Their talk pushed the alternative idea that this RNA was a precursor on the way to being transformed enzymatically into DNA. Much more exciting to the audience was Arthur Kornberg’s report that his St. Louis lab had possibly observed genuine DNA synthesis in extracts prepared from E. coli bacterial cells. The precursor nucleotides involved and the enzymes to pop them together were possibly up for grabs.

  The session on nucleic acid chemistry was opened by Erwin Chargaff, who said that too much attention was now being given to nucleic acids at the expense of other worthy cell constituents, such as proteins, polysaccharides, and lipids, further warning that the deeper nucleic acids entrap us, the darker it becomes. In following him, Francis, then wearing his RNA tie, wisely did not rise to Chargaff’s caustic bait. He stuck almost schoolmaster-like to DNA’s conformational details, emphasizing that for any molecular model to be seriously considered, its creators must build a stereochemically satisfactory proposal. Here he slapped down another jealous biochemist’s remark earlier that “real research is done at the bench and not by playing with metal models.” Only briefly did Francis allude to possible codes, not having the heart for speculations without facts.

  When my turn to speak came, I realized only too well that my poly(A) structure had no real significance for the assembled audience because real RNA itself could not have a similar structure. More exciting was Alex Rich’s report that poly(A)–poly(U) double helices form if samples of poly(A) and po
ly(U) are mixed. Conceivably the resulting double helices are DNA-like, but Alex thought his X-ray patterns favored the two chains running in the same direction like poly(A), not in the opposite direction like DNA. In either case, Alex relished Julian Huxley’s recent reference to his result as molecular sex—two molecules that embrace each other as soon as they meet.

  Francis Crick wearing his RNA tie in Baltimore, 1956

  At the meeting’s end, I drove back to Washington with Alex, where my brother-in-law Bob Myers would meet me to take me to his and Betty’s home in Falls Church, near where he worked for the government. Soon they would be returning to the Far East, this time to Indonesia, for work in the U.S. Embassy at Jakarta. When their newborn second child, Holly, was able to travel, they would be off. Knowing that Bob’s 1954 MG-TF had to be sold, I wrote a check for his asking price of $1500 and drove it several days later to Cold Spring Harbor.

  With most students gone, summer was not the time to be in Cambridge, Mass., at least in comparison to Cold Spring Harbor where many clever visiting scientists would be in residence. Salva Luria was teaching the Phage Course that was following a new course on Fungal Genetics for which Guido Pontecorvo was the main instructor. When I arrived I found it already in progress and Ponte anxious during breaks to play Ping-Pong under the Blackford Hall dining porch. Also back, after several years of absence, was Susie Mayr washing dishes for the summer courses. Anxiously, I asked about her sister Christa and learned that over Easter she had travelled deep down into Italy and was expected back in late August for several weeks of rest before starting her senior year at Swarthmore. Susie knew that as the summer ended, I would be on tenterhooks, but she was not now privy to Christa’s confidence and didn’t want to predict her arrival mood.

  At the wedding of JDW’s cousin, Ruth Watson, to John Martin in New Haven, November 1955: (from left to right) William, James Watson Sr., Margaret Jean Watson (mother), Betty Myers (sister), and Betty Watson (aunt). The car is the MG that JDW later bought from his brother-in-law, Bob Myers.

  In Jones Laboratory, I had quickly set up a primitive phage lab, helped by my first graduate student, Bob Risebrough. Born in Canada, Bob had gone to Cornell University as an undergraduate because of an interest in ornithology. Now he wanted to move on, like I had almost a decade earlier, to experiments with phages. I suggested he spend the summer learning how to work with the very small phage ΦX174 that might have an equally small DNA molecule. Luria’s lab in Urbana still had this little-studied phage in storage, and a sample was quickly sent so that we could soon prepare it in large amounts. Jones Lab, however, proved not the place for phage purification, although Bob isolated several phage mutants for study over the rest of the summer.

  A letter I posted back to Belinda Bullard in Cambridge, England, was quickly answered with the news that she had just visited Peter and Julia Pauling at their Clapham home in London. They had moved into larger quarters to give Peter space to be far away from their forthcoming baby. It was now due in mid-August. Belinda thought their new home nice except for two rooms in the middle—in a muddle that Julia, who was always tidy, could not have created. Sprawled across them was a huge electronic set-up that served as Peter’s gramophone. Not wanting to spend the summer under her mother’s eye, Belinda first eyed Alice Roughton’s house in Adams Road. Diverse paying guests stayed there, so she thought it might be an amusing experience for the summer. When she visited, its door was open and she popped in to find a son of the family, Geoffrey, in black trousers, a stiff shirt, and a black bowler hat. His defunct poetry magazine had been called Oasis, but now he did statistics of some sort. Most of the rooms had more than four guests, and two old Rolls-Royces were in the garage. Next door lived Alice Roughton’s sister with seven children and a bearded husband, who once wrote a book on breadmaking. In the end, Belinda thought it prudent to rent a room at 27 Green Street, across the street from Wally and Celia Gilbert at No. 24.

  Further Green Street news came from Celia, who reported that on the July day she wrote they had been vouchsafed 10 minutes of sunlight with the weather freezing all the time. Happy to have gotten my unexpected letter from Long Island, she jumped at my offer to make her my technician when my Harvard lab started up in the fall. Pleased that I so magnanimously wanted to employ a cretin, as she put it, she wondered what rules might exist about their employment permission from a doctor or nearest relative. Here I most certainly had Wally’s wholehearted approval for it would mean Celia learning some science and making her, in his eyes, a more worthy mother of Gilberts. Much less important than Wally agreeing was the generous salary that would come out of my NSF grant. Celia had already immersed herself for half an hour in a Belinda-lent chemistry book where she found the words covalent bonds, ionic bonds, anions, and cations, the latter of which sounded suspiciously to her like a dirty word.

  Having read Russian short stories and felt how wretched a sinner she was, Celia was on to Balzac and appreciating how viciously and terribly nearly everyone else behaves. From a BBC radio program on Henry James, she knew his agony in deciding how to address the Army and Navy store in London to order six pounds of Oxford marmalade. For the boat voyage she was holding back reading his Tragic Muse to read it on, ugh, the “D” deck. Then when home, she must show off to me her masterful gingerbread.

  Back in Cold Spring Harbor, I increasingly looked forward to a visit up from Washington by Alex and Jane Rich. Alex would then let me know whether he still thought the two chains of his poly(A)–poly(U) double helix ran in the same direction. To Jane, I could let out my increasing jitters as Christa’s return-home time got closer. They were coming up for the wedding of the daughter of her Ames aunt, whom I had met earlier in London and who lived with her family in a house befitting the daughter of a J. P. Morgan partner. The wedding was to be at St. John’s, the beautiful wooden-steepled 1840s church, built by the Jones family, then Long Island’s most prominent family. Until Jane arrived, I had hoped to crash the wedding reception, if not the wedding itself, to look over daughters of the lab’s wealthier neighbors. Jane, however, said no, her mother would not like me stepping around her family’s social code.

  But she gave me the cheerful alternative of meeting later that evening Ann McMichael, the pretty small blonde who had so captivated me the summer before on the shore of Lake Geneva. That Ann then had so warmly responded to my bug-sickened form made me wonder whether her marriage was that strong. So I was not surprised to hear that she had separated from her husband and the marriage was soon to end. But I didn’t warm to the news that Ann had a new male friend and was anxious especially for me to meet him.

  I knew that Dick Feynman was nearby, talking with high-energy theoreticians at the Brookhaven National Lab further east on Long Island, so we asked him to join our party. Several weeks before I had gone there to have supper with him and learned that his marriage to Mary Lou had fallen apart. An art historian, Mary Lou wanted life with a dignified professor, who wore ties and with whom she would look in place in her high heels. The drums and Dick’s unrestrained antics at student-dominated parties increasingly rubbed her up the wrong way, and earlier this year he could take no more of their constant arguing. On the phone I told him that a pretty, now-free girl I had met in Switzerland would be there for him to gaze upon.

  At the Chinese restaurant in which we gathered about a large, round table, Dick could only be his volatile, show-offish self. It was virtually impossible for him to enjoy himself without being the life of the party. When the long supper was ending, Dick took me aside and asked what I saw in Ann. Gone, at least temporarily, was the youthful thirst for life that let Ann share hands with me in an apple orchard beneath the Alps.

  August was in its last week when, on a Tuesday evening, Susie Mayr told me that terrible news had just come in a letter to Ernst and Gretel. I instantly feared that Christa had fallen in love with a German student and would not soon be coming home. But the news was much, much worse. Christa’s letter revealed that she was pregnant and t
hat the father was an engineering student she had met in Munich. The baby was in no way coming by design. Nonetheless, she wanted to have the child and marry the father in Germany after a month’s visit home to see her parents and Susie. Most importantly, she was not doubting her decision and did not want to come home to give her parents the chance to try to change her mind.

  Susie was virtually in tears as she talked, and I became too choked up to reply coherently. Learning that Ernst was soon leaving their New Hampshire farm to come down to Storrs in Connecticut for the annual meeting of the Genetics Society, I arranged to meet him two days hence. There I found him fatalistic, telling me how strong-willed Christa could be and revealing that her letters over the past eight months had much worried him. Particularly bad was her going alone to Italy over Easter, with so little concern about falling into danger, personal or otherwise. In his opinion, she was much too immature to have a baby by a youth that she had known for such a short time. But he did not know how to convince her of this. After she was home, now in only a few days, he and Gretel would do the best they could to keep Christa from ruining all her chances for a meaningful future.