Genes, Girls, and Gamow

by James D. Watson

  No one from abroad expected that this congress would provide anything but a chance to see communism in action. Soon, however, I heard rumors that there might be an unexpected bombshell talk by Marshall Nirenberg from the National Institutes of Health. It was not one of the main presentations, and only a few individuals, including Alfred Tissières and Wally Gilbert, were drawn to its presentation through the title “The dependence of cell-free protein synthesis in E. coli upon naturally occurring and synthetic template RNA.” Using Alfred’s improved recipe for cell-free protein synthesis, Nirenberg and his German colleague Heinrich Matthai had found over the past several months that addition of poly(U) promoted the synthesis of polypeptides made up exclusively of the amino acid phenylalanine.

  When François Jacob heard about the experiments from me over breakfast the next morning, he thought I was perpetuating a practical joke. But Nirenberg and Matthai had done their experiments well, and Francis hastily arranged a big lecture on the last congress day that let Nirenberg convince as well as stun most in the audience. From that moment on, it seemed likely that the genetic code would soon be completely cracked through observing the polypeptides made in cell-free systems programmed with appropriate synthetic polyribonucleotides.

  Wally and I flew east, not west, from Moscow. He was on his way to Pakistan, where his economist father worked for the Ford Foundation, while I was on a round-the-world ticket that would let me go to the great temples at Angkor Wat with my sister Betty, whose husband was then attached to the U.S. Embassy in Cambodia. En route I wanted an Afghanistan experience and in Kabul learned that fresh melons were not always what they seemed, often having weight added by immersion in the water running under the streets. To stay healthy, I temporarily joined the International Club, where I supped with two Americans who let on they were economists at the Kabul Embassy. Sensing that they might be otherwise, I asked them whether they knew my brother-in-law, Bob Myers? Their negative answer I would have forgotten had I not later bumped into a friend of Betty’s on a ferry in Hong Kong. He told me that he was just with colleagues who had met me in Kabul.

  After his return from Moscow, Wally’s time away from teaching physics became exclusively directed to messenger RNA. He got poly(U) samples from Paul Doty and showed that several ribosomes can function on single mRNA molecules, thereby explaining why there was so little mRNA in cells. At the same time, Alex Rich observed aggregates of ribosomes (polysomes) in hemoglobin with four to five ribosomes simultaneously translating the relatively short messages that coded for the small globin chains with 155-amino acids.

  Meanwhile, Francis Crick and Sydney Brenner were completing genetic experiments in Cambridge to prove their hypothesis of the year before that acridine dyes, like proflavin, cause mutations by inserting or deleting base pairs. As 1961 progressed, and not knowing of Dick Feynman’s results, they independently found that suppressors of r2 mutations when present by themselves are also r2 mutants. Whereas Dick thought r2 suppression reflected pairs of changed amino acids neutralizing each other, Francis and Sydney believed their results arose from the genetic code being read in groups of bases, probably three, starting from a defined spot. The addition of a base would alter the reading frames beyond, as would the deletion of a base. If they were correct, suppression of addition (or deletion) mutants would lead not to two separate amino acid replacements but to a stretch of changed amino acids between sites of insertion and deletion. Proof that they were right came from their finding that all their proflavin-induced suppressor mutations fell into two classes (+ or —) with ++ or — combinations never suppressing. And by finding that groups of three nearby +(—) mutations frequently lead to normal phenotypes, they showed that amino acids are specified by groups of three bases (a codon). Sensing the great importance of this result, the editor of Nature saw that their resulting, quickly written paper appeared in the last issue of 1961.

  Increasingly by then I was preoccupied by the White House Presidential Scientific Advisory Committee (PSAC). Formed during Dwight Eisenhower’s last years as a response to the launch in 1957 of the first Soviet Sputnik, it was initially chaired by the Russian-born George Kistrakowsky, long a Harvard professor, whose labs were below Paul Doty’s. George, who was then still on the committee as was also Paul, made my day soon after I returned from my world trip by asking if I would help PSAC in its oversight of our biological warfare effort. No obvious red skeletons popped up in my past and by December I had a White House pass letting me into the Executive Office where PSAC’s office was now headed by MIT’s sagacious electronics expert, Jerry Wiesner. Two floors above and down the corridor were offices for junior members of McGeorge Bundy’s National Security Council. In one sat Diana DeVegh, whose job seemed to owe less to her talents as a budding Arabist than to her dinners with the then junior senator from Massachusetts when she was at Radcliffe.

  Diana was a senior (in her final year at college) when we first met at a party given by the British-Israeli chemist, David Samuels. A postdoc in Harvard’s Chemistry Department, he would eventually assume the title first held by his illustrious grandfather Viscount Samuels. To my surprise he told me that he and Rosalind Franklin had been cousins and that he had admired her attempts to live by her brains alone and not through her privileged family connections I had not known about before.

  For much of spring 1962 I was back on sabbatical leave in old Cambridge where I lived in Churchill College as a visiting fellow. The college had recently been formed with Sir Winston’s blessing to provide more science at Cambridge and Francis became one of its founding fellows. But when they decided to build a chapel, using funds specifically designated for this purpose, Francis very publicly resigned, saying he saw “no reason to perpetuate mistakes from the past.” Later he gave 75 guineas (£100) to the Cambridge Humanists to sponsor a prize essay on “What shall be done with the college chapels?” The winning essay saw several different futures for them, including swimming pools.

  Francis and Sydney had just recently moved their labs away from the Cavendish to the newly constructed Medical Research Council (MRC) Laboratory for Molecular Biology at the new Addenbrooke’s Hospital site. The Queen opened the new building and on her tour around she received brief explanations of the three-dimensional models of hemoglobin and myoglobin whose structures Max Perutz and John Kendrew had recently triumphantly solved. Initially the double helix was to be presented by Francis, but he balked, saying that the more appropriate person to open the lab was her husband, Prince Philip. So I took on his chore and when asked by the Queen what she was looking at, I took two minutes to summarize DNA and horses.

  I returned to the States in time for the annual Cold Spring Harbor Symposium in June. Virtually everyone of importance in the animal-virus world was there. The meeting started with a clever structural paper by Don Caspar and Aaron Klug that intellectually extended the ideas on polygonally organized viruses that Francis and I put forward six years before. Tumor viruses were coming into prominence with Renato Dulbecco and Michael Stoker beginning to explore how the newly found polyoma virus makes cells cancerous. Also present was André Lwoff, whose talk on polio research had its origins in his 1955 visit to Dulbecco’s Caltech lab. While standing in the long food line, André, then 60, could not help but notice the checkout girl, the cook’s daughter Amy, whose undeniable beauty was so at variance with that of her mother. Towards the meeting’s end, he paid her the compliment of saying he wished he was 20 years younger. In reply, Amy said that 30 years would be better.

  During the summer of 1962 Alfred Tissières was back at Harvard from Europe where he had just become a professor in Geneva. Virginia went on to Denver to be with her mother for the birth of their first child. Embellishing the lab then was urchin-like Radcliffe student Pat Collinge. I had been told she needed a summer salary and eagerly found her a lab job. Pat’s blue eyes proved a magnet that kept me not too far from the lab that summer. Near August’s end, I persuaded her to drive with me to Woods Hole before she joined her boyf
riend, then out on Cape Cod. At Woods Hole, in Albert Szent-Györgyi’s house, Pat typed out the first page of the book that I initially called “Honest Jim,” and whose first chapter began with the words “I have never seen Francis in a modest mood.”

  In early October, the news came out of Stockholm that Francis, Maurice Wilkins, and I had received the 1962 Nobel Prize for Physiology or Medicine. That Maurice was included pleased both Francis and me, but we had to wonder how the prize would have been divided if Rosalind Franklin had not died so tragically young. Then, as today, the Nobel’s rules preclude dividing any given prize among more than three individuals. My sister Betty came with me to the almost weeklong ceremonies, as did my father. We stayed in the Grand Hotel that looks out over water to the Royal Palace. Also there were John Kendrew and Max Perutz, who had been chosen as that year’s winners of the Nobel Prize for Chemistry. Geo Gamow’s Russian friend, Lev Landau, the 1962 winner of the Physics prize, sadly could not come—not because of communist fears that he would bolt, but a tragic recent road accident that had left him badly impaired mentally and physically. I would never have the opportunity of seeing why Gamow thought our personalities so similar.

  Over Christmas 1962 I was at Verbier, the Swiss ski resort that Alfred Tissière’s brother helped finance and from there flew to Scotland to join the Mitchisons at Carradale for New Year’s Eve. Later, in Geneva, I met John Kendrew and we went out together to CERN (then called Conseil Européen pour la Recherche Nucléaire, hence the acronym, but now the European Laboratory for Particle Physics). Leo Szilard was temporarily there, having precipitously fled Washington, D.C., with his wife Trudy, fearing a nuclear catastrophe at the time of the Cuban Missile Crisis. Leo was keen to get started in Europe a Cold Spring Harbor–like lab that could hold courses and meetings and for important research. He wanted Vicky Weisskopf, in Geneva on leave from MIT, to head CERN and to tell us what problems might come up in founding and then funding a CERN-like organization for molecular biology.

  At Geneva, my return flight was delayed due to a snowstorm over southern England, and I found myself next to Janet Stewart, the statuesque Girton student whom I originally met through Linda Pauling. For several years previously I had seen much of her when she and Gidon Gottlieb shared a flat near Harvard Square on Boylston Street, while he did further studies at Harvard Law School. The year before, though, they had gone their separate ways, neither able to keep each other in the style of life that their intellects needed. With Janet on the plane was a youthful-looking Etonian barrister, with whom she had been on a skiing holiday and whom she later married.

  The June 1963 Cold Spring Harbor Symposium saw the big labs of Marshall Nirenberg and Severo Ochoa racing to crack the genetic code through varying the base compositions of their synthetic RNA templates. Using this route, roughly half of the potential 64 codons (AAU, AAC, AAA, AAG, etc.) now had amino acids assigned to them. At the meeting, Wally Gilbert from our lab talked about polyribosomes and how growing polypeptide chains are held into ribosomes by their car-boxyl terminal transfer RNA molecules. And Leo Szilard again pigeonholed symposium attendees for facts he later wanted to put more cleverly together. The occasion provided the biggest gathering yet of the RNA Tie Club with five of its members present, including Geo Gamow and his ever-present whisky glass.

  That fall, my sister Betty was living again in Washington, her husband having been posted back from Cambodia. When briefly down for a PSAC meeting, I met at their home John Richardson, whose removal the week before as the CIA Station Chief in Saigon was widely taken to mean that the USA no longer backed the South Vietnamese Government. Two weeks later, again on PSAC business in the Executive Office Building, my meeting was interrupted by the news that President Kennedy had been shot in Dallas. Too soon afterwards we were told he was dead. That night I had dinner with the Szilards. By evening, Leo had already removed Jack Kennedy from his mind and was worrying how to influence Lyndon Johnson’s future decision about nuclear weapons. I had no wish to watch the funeral cortège pass down Pennsylvania Avenue and was back at Harvard by the time the funeral mass had started. I knew that my return visits to Washington would never be the same.

  Bad news came again soon when my father, then only 63, suffered a stroke and it was unclear whether he would ever walk again. But over the next several months he became able to move with a cane and continued living next to me in Cambridge until his death, seven years later, from smoking two packs of Camels a day for 40 years.

  Meanwhile, my Nobel monies had gone to make a $17,000 down payment on an early-nineteenth-century wooden house within walking distance of Harvard Square. Paying off the mortgage early was now within my means due to the widespread acceptance of my new book, The Molecular Biology of the Gene, published in time for the previous fall’s college classes. It was the first introductory textbook aimed at college students to emerge from our DNA revolution. In its first year, royalties effectively equaled my salary as a Harvard professor. So, even more, was I in want of a wife.

  Whenever I could go down to New York I would have dinner with Gidon Gottlieb, now practicing law in the city and living with his new wife Antoinette, who originated from Geneva, in a penthouse on Sheridan Square in Greenwich Village. Early in 1965 I mentioned to them that I had just seen in Boston Salvador Dalí’s massive new painting Galactosidal Nucleic Acid—Homage to Crick and Watson. Jokingly we mused whether Dalí might be the appropriate artist to illustrate “Honest Jim.” We knew that Dalí and his wife Gala lived during the winter in the St. Regis Hotel in New York, and the three of us taxied there in the hope of meeting him. From the hotel lobby I sent up a hastily scrawled message “The second brightest person in the world wishes to meet the brightest,” and signed it Jim Watson. Within minutes he was in the lobby and, in French (which the Gottliebs understood), asked me to lunch several days later at his hotel’s King Cole Restaurant.

  Initially I felt awkward over our small table as Gala tried to translate to me Dalí’s interest in holograms. Then, without warning, a super-pretty young girl with long blond hair came to our table and told me how pleased she was that Dalí was letting her meet the discoverer of DNA. She was an actress on the popular TV program Peyton Place, but as I did not then own a TV set I could not connect her incredibly fetching face and voice to her name. Then all too soon, unfortunately, she left to catch a plane for Los Angeles. Believing her to be at most 15 years old, I felt depressed that I, now 37, was unlikely ever to get to know her. Only two years later did I realize who the blond young angel was. After reading a magazine article about Dalí, I saw him at Knoedler’s 57th Street Gallery at an exhibition of his recent paintings. I told him I recognized her, and he smiled as he said “Oh, Mia.”

  From mid-October 1965 through into the New Year, I was across the Atlantic in old Cambridge to learn more facts from Francis so that I could complete “Honest Jim.” Only the final chapter remained unfinished when I was briefly back in Harvard early in January. In only two days I had polished it off, ending with the words “I was 25 and too old to be unusual.” Then I flew off for a six-week lecture tour sponsored by the Ford Foundation of East African universities. Afterwards I went on to Geneva for several months in Alfred Tissières’s lab, then largely devoted to ribosome studies. There Alfred told me that working for him was an attractive Iranian girl called Nasrine Chahidzadeh, who wanted to go to the States. So I took her out to dinner where she told me about her chemistry studies in Zurich. Then she wanted to know more about the Kennedys, having just met Teddy at a large lakeside house in Geneva. Our dinner had not ended when I let Nasrine know there was a job for her at Harvard if she wanted it.

  Bringing me back to the States in early June 1966 was the Cold Spring Harbor Symposium on the Genetic Code. By then, all the codons had been solidly established, helped much by Gobind Khorana’s combination of chemical and enzymatic tricks for making synthetic RNA of known repeating sequences. This symposium was very much one for Francis Crick to dominate—rather as I held forth at th
e 1953 gathering and Jacques Monod and Sydney Brenner did in 1961. The tone was set by Crick’s opening address entitled “Yesterday, Today and Tomorrow.” At the meeting’s end there was a mood of great triumph at the cocktail party on the Blackford lawn, which coincided with Francis’s fiftieth birthday. Knowing it was a more than noteworthy occasion, I had driven earlier with Paul Doty’s student Bob Thach to Entertainments Unlimited in Levittown. There, from a book of pictures, we chose “Fifi” as appropriate for a coming-out-of-a-cake-like act under the Blackford porch. Luigi Gorini, in the know, had his camera on hand to record Francis’s laughing reaction to his birthday present.

  Increasingly the potential gaiety of any such gathering was diminished by the thickening cloud of the escalating American involvement in Vietnam. We felt that Harvard itself was in trouble. To try and explain what our White House policy was, in June 1965 McGeorge Bundy came to Harvard and spoke to a packed Memorial Hall student audience. Sitting next to Paul Doty, I felt at first dissatisfied with Bundy’s answers and, later, sad, not wanting to believe that my former Harvard protector had become a spokesman for a war that could never be won. To my relief, Betty’s husband was no longer associated with our Southeast Asia doings. Long wanting to have a try at journalism he had just become the publisher of the new Washington Magazine that he founded with his University of Chicago roommate, Lauchlin Phillips.