Genes, Girls, and Gamow: After the Double Helix

FROM THE PUBLISHER (Alfred A. Knopf): Immediately following the revolutionary discovery of the structure of DNA by James D. Watson and Francis Crick in 1953, the world of molecular biology was caught up in a gold rush. The goal: to uncover the secrets of life that the newly elucidated molecule promised to reveal. Genes, Girls, and Gamow is James Watson's report on the amazing aftermath of the DNA breakthrough, picking up where his now classic memoir, The Double Helix, leaves off.

Here are the collaborations and collisions of giants, not only Watson and Crick themselves, but also legions of others, including Linus Pauling (the greatest chemist of the day), Richard Feynman (the bongo-playing cynosure of Caltech), and especially George Gamow, the bearlike, whiskey-wielding Russian physicist, who had turned his formidable intellect to the field of genetics; with Gamow--an irrepressible prankster to boot--Watson would found the legendary RNA Tie Club.

But Watson--at twenty-five already the winner of genetic research's greatest jackpot--is obsessed with another goal as well: to find love, and a wife equal to his unexpected fame. As he and an international cast of roguish young colleagues do important research they also compare notes and share complaints on the scarcity of eligible mates. And amid the feverish search for the role of the then still mysterious RNA molecule, Watson's thoughts are seldom far from the supreme object of his desire, an enthralling Swarthmore coed who also happens to be the daughter of Harvard's most eminent biologist.

Part scientific apprenticeship, part sentimental education, Genes, Girls, and Gamow is a penetrating revelation of how great science is accomplished. It is also a charmingly candid account of one young man's full range of ambitions.

Chapter 1

Cambridge (England): April 1953

Although my hair was properly long and my accent toned to suggest almost an English origin, Odile Crick told me I had still far to go before I would look right walking along Cambridge's King's Parade, much less looking purposefully indolent in one of its college gardens. My appearance would not have mattered if I were the same as a month ago-an unkempt slender figure who said what I thought as opposed to what good manners required. But now that Francis Crick and I had given the world the double helix, Cambridge in its own quiet way was bound to ask what we looked like. The time had come to acquire at least one set of clothes that would go well with Francis's Edwardian elegance. I was not trusted to act alone and Odile accompanied me to the men's clothing shop across from the chapel of John's (the College). My ill-fitting American tweed jacket was thrown out and replaced by a blue blazer and associated gray trousers. They would much better express my new status as the co-winner of a very great scientific jackpot.

The DNA molecule we had found two months before-in March 1953-was far more beautiful than we ever anticipated. With the two polynucleotide chains held together by adenine-thymine and guanine-cytosine base pairs, DNA had the complementary structure needed for the gene to be exactly copied during chromosome replication. When 1953 started, finding out what genes look like and how they replicate were two of the three big unsolved problems in genetics. Seemingly coming from nowhere, Francis and I had now grasped both. At times I virtually had to pinch myself to prove that I was not in the middle of a wonderful dream. But I was not, and so the possibility existed of a grand slam in which Francis and I also worked out how genes provide the information to make proteins.

By the flip of a coin, our names in the original manuscript had the order Watson-Crick instead of Crick-Watson. So several Cambridge wags now could refer to our DNA model as the WC structure. They suspected that our golden helix would be found tainted and destined for dumping down the water-closet drain.

I had become monomaniacal about DNA only in 1951 when I had just turned 23 and as a postdoctoral fellow was temporarily in Naples attending a small May meeting on biologically important macromolecules. There I learned from a mid-thirtyish English physicist called Maurice Wilkins that DNA, if properly prepared, diffracts X-rays as if it were a highly organized crystal. The odds were thus good that DNA molecules (genes) themselves have highly regular structures that conceivably could be worked out over the next several years. Briefly I considered asking Wilkins if he would let me join his London lab at King's College on the Strand, but my attempts to talk with him after his lecture elicited no enthusiastic response and I dropped the idea.

Instead, through the intervention of Salvador Luria, my Ph.D. supervisor at Indiana University, I was taken on five months later at the Cavendish Laboratory in Cambridge to work with an English chemist, John Kendrew. He was helping the Austrian-born chemist Max Perutz lead a small research group supported by the Medical Research Council (MRC) called the "Unit for the Study of the Molecular Structure of Biological Systems." Started in 1947, its scientists used X-ray methods to work on the three-dimensional structures of the oxygen-carrying proteins hemoglobin and myoglobin. In going to join the group, I hoped to expand the attention of the unit to DNA, so that they would let me work on it, instead of a protein, once I had learned X-ray diffraction techniques.

My crystallographic career, however, would have likely soon aborted if Francis Crick had not been in the lab. From the moment I arrived, he treated me as if I was a much younger brother in need of help. Then 35 years old, Francis was effectively unknown outside Cambridge, having joined the unit only two years before. Already Francis's penchant for theory had made him a powerful addition to the team's protein-solving efforts. His first major success came soon after I arrived, when that October he helped work out the theory for diffraction from helical objects. Even so, Francis could not anticipate a long-term future within the unit, because the week before he had badly upset the head of the Cavendish Laboratory, Sir Lawrence Bragg, by arguing that he, not Bragg, first saw a potential new way of analyzing protein X-ray diffraction patterns. To say the least, Bragg did not like the implication that he had pinched a younger colleague's idea. In fact, on that ill-fated Saturday morning, Francis realized that neither his nor Bragg's precise approaches were that good and that only isomorphous replacement methods held out real hope.

That fall of 1951 we had no reason to hope that we would be more than minor players in DNA research. The experimentalists at King's College London-Maurice Wilkins and Rosalind Franklin-were set to provide the definitive evidence for choosing one DNA model over another. But over the next year, their personalities clashed badly, and Maurice found himself driven away from X-ray analysis of DNA. Soon Rosalind had all the cards needed to solve the structure, provided she co-opted the model-building approach that Francis and I so passionately argued for. Here her greatest mistake was being put off by Francis's strong personality that she thought masked a bumptious overextended intellect.

Even less predictable was the inexplicable chemical botch that Linus Pauling, then universally perceived as the world's best chemist, made with his ill-conceived triple-stranded DNA helix. Late in 1952, we had become apprehensive when Linus's son, Peter, who had newly arrived in the unit to be a research student with John Kendrew, told us that "Pop" was working on DNA. Only 18 months before Linus had humiliated the Cambridge group with his a-helical fold for proteins. We breathed much, much easier in February 1953 when we read a manuscript from the California Institute of Technology (Caltech) and saw that Pauling's DNA model was way off the mark.

Quickly I raced into London to alert the King's group that Pauling's new helix was a botch and we should expect him quickly to devise a better model. Rosalind, however, thought I was being unnecessarily hysterical, telling me in no uncertain terms that DNA was not helical. Afterwards, in the safety of his office, Maurice-bristling with anger at having been shackled now for almost two years by Rosalind's intransigence-let loose the, until then, closely guarded King's secret that DNA existed in a paracrystalline (B) form as well as a crystalline (A) form. In his mind the cross-shaped B-diffraction pattern, shown on the X-ray he then impulsively took out of a drawer for me to see, had to arise from helical symmetry.

Almost perversely, it was Linus Pauling's entry into the DNA game that made it possible for Francis and me to find the double helix. In November 1951, before it was clear that Pauling was out to get the DNA prize, Francis and I had been told by Sir Lawrence Bragg that DNA was off limits to the Cambridge unit because it belonged to the workers at King's. Even 14 months later, bad memories still existed of our awkward first attempts to build DNA models. But we then quickly gave up trying to guess the DNA structure and even passed details of the molds needed to build models to Maurice Wilkins. By now appraised of the B-form's existence, Bragg wanted Francis and me to have another go at building models. He hoped that our efforts-possibly coordinated with those in London-would generate the right answer before Pauling recovered his senses.

No one then could have anticipated that in less than a month Francis and I alone would have found the answer and one so perfect that the experimental evidence in its favor from King's almost seemed an unnecessary accompaniment to a graceful composition put together in heaven. Our writing of the tiny manuscript for Nature that would announce the double helix seemed even then an historic occasion. My sister Elizabeth, who had followed me to Europe two years before, did the typing, with Odile Crick using her artistic talents to draw the intertwined, base-paired, polynucleotide chains. Together with two experimental manuscripts from the warring King's groups of Wilkins and Franklin, it was dispatched to Nature's editor by Bragg on April 2 and published only slightly more than three weeks later on April 25.

Our most unanticipated success was a big relief to Betty, my sister, and Odile. My proclivity for super dreams had clearly long worried Betty, who feared that I would never adapt successfully to the world of ordinary people. Odile, on the other hand, no longer had to worry about having to leave Cambridge. Bragg could not force Francis to leave the lab after he had helped give England the double helix. And, even though it was then ordained that the Cricks go for a year to Brooklyn, Odile would not have to consider the awful fate of staying on.

Dinners with the Cricks at their house in Portugal Place became even more spirited occasions after our success, with Odile often bantering me about my better prospects of getting the perfect girlfriend. Before the double helix, it was easy to meet the foreign girls who were in Cambridge to learn English. But I sensed it would be much better to try and get to know the undergraduate English girls at Girton or Newnham-at least I might understand what they said. But no one I knew then had any real contacts at these women's colleges. The correct tack for me might have been to seek out an attractive tennis player. But Francis, though his father played at Wimbledon, had long ago given up outdoor sports and neither he nor Odile knew any girl, blond or otherwise, who hit the ball hard. Happily by the time of our discovery, and on my own initiative, I thought I might have located the girlfriend appropriate for my new fame.

The previous August, in the Italian Alps, I had met a good-looking English girl called Sheila Griffiths, who was living with a mountaineering family. As luck would have it, we started talking only two days before I was due to depart, one of which she spent ascending Monte Disgrázia that loomed above the tiny village of Chiarregio. Born in Wales, Sheila was in Italy to improve her Italian in return for looking after two children and hoped to go to Rome when the summer ended. She came from a mining heritage and her father, Jim Griffiths, was a Labour Member of Parliament. She had several more weeks in the mountains and worried about keeping busy if bad weather settled in. So I lent her my copy of Aldous Huxley's Point Counter Point and, when briefly in Milan, bought copies of The Economist and New Statesman to post on to her.

During the fall I kept hoping to hear from her, having given her my Clare College address when we parted because then she did not know where she would be living in Rome. Just before we found the double helix, however, she sent me a letter from the Dolomites where she was learning to ski with her two charges. At Easter she was coming permanently back to England and enclosed the telephone number of her family's home in Putney. Before we parted in Italy, I had told her that DNA had to be at the heart of life. Now, in April 1953, this was no longer a conjecture: the double helix would soon be a, if not the, fact of life.

2

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 six pence, 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 DelbrÃ?ck, 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.