by James Watson
Klaus's decision was already 90 percent made when Derek and Sissela Bok invited Liz and me for a late March Friday night dinner at Elmwood, the gracious old wooden house just off Fresh Pond Parkway where they lived with their four children. Upon Derek's becoming president, they chose not to live in the formal Quincy Street fishbowl successively occupied by Lowell, Conant, and Pusey Two years younger than I, Derek had concluded three very successful years as dean of Harvard's Law School. A graduate of Stanford, he was the first president of Harvard not a product of the college. That evening I tried to forget about the animal cell biology fiasco and Harvard's lack of a tumor virus future. I realized there was no longer a good reason for Cold Spring Harbor and Harvard to remain closely connected. Derek graciously kept our conversation on other matters, knowing only too well that my heart was now mostly at Cold Spring Harbor. Harvard had no one leading it into the future in the way David Baltimore was blazing the way for MIT biology.
Two weeks later, I drove over to the glass-faced MIT biology building for a meeting hosted by Paul Berg. There, with David Baltimore's help, he assembled a small group to discuss implications of the powerful new recombinant DNA technology developed at Stanford. Phil Handler, the president of the National Academy of Sciences, had asked Paul to come up with an appropriate response to a letter published in the September 21,1973, issue of Science. The academy had been called on to offer guidelines for recombinant DNA experiments that might create biohazards not only for the lab worker but also for the general public. That morning our small group, which included Dan Nathans and Norton Zinder, concluded the matter would best be dealt with by a much larger group assembled at the same Asilomar, California, site where we had considered potential biohazards of tumor virus research the year before. Until Asilomar II could be held, likely early the next year, we proposed a worldwide moratorium on recombinant DNA experiments in a letter to the journals Nature and Science. I then visualized the Lab publishing Asilomar II's proceedings. Unlike our first biohazard book, this one I expected to make real money.
All the world's major tumor virologists assembled three months later for the Lab's annual early June symposium. Joe Sambrook organized the DNA tumor virus sessions, and David Baltimore put together the ones on RNA retroviruses. Between Renato Dulbecco's introductory talk and David's concluding summary, there were 116 presentations, out of which 101 manuscripts were generated. They would fill our first two-volume symposium proceedings, consisting of almost twelve hundred pages. Though no scientific bombshell exploded, the meeting's highly charged atmosphere made it likely that a deep truth would emerge at any moment. More presentations came from Cold Spring Harbor scientists than from the faculty of any other institution, even London's better-funded Imperial Cancer Research Labs in Lincoln's Inn Fields. Klaus Weber and Mary Osborn notably reported upon their purification of the SV40 antigen. In their talk they provided strong presumptive evidence that the T antigen was the product of SV4o's A gene, one that functions early in the SV40 life cycle as well as in SV4o-transformed (cancerous) cells. Further studies might soon convincingly show it to be the primary cancer-causing genetic unit on SV4o's small circular chromosome.
I spent much of the remainder of the summer on Martha's Vineyard preparing the third edition of The Molecular Biology of the Gene.
Next to our old farmhouse was a small barn, whose large central room provided an ideal writing space. I was getting invaluable feedback from several science-oriented Harvard and Radcliffe students, who later extended the glossary and corrected the final proofs. Doing the many needed new illustrations was Keith Roberts, by then running his own plant cell biology lab at the John Innes Institute in Norwich, England. As a postdoc at Cambridge five years before, he had created the new drawings for the second edition as well.
Over the following academic year, I was again on leave, working full time at Cold Spring Harbor at a salary identical to what Harvard would have paid me for teaching. Our settled residence in Cold Spring Harbor allowed Liz to take two classes per week at the New York School of Interior Design. Often sitting near her was the petite, blond Barbara Lish, wife of the writer Gordon Lish, then America's most influential arbiter of fiction, whom we befriended. Most unexpectedly we bumped into the Lishes at an early December gathering of intellectuals on the Florida coast. Arthur Schlesinger, Gunnar Myrdal, Saul Bellow, Vernon Jordan, and I had all been assembled just north of Daytona Beach with the unexpressed purpose of drawing attention to ITT's big beachfront development called Palm Coast. It was still a day when public intellectuals could sell real estate. Attracting us to this most unlikely gathering was the generous $4,000 honorarium, a much more substantial monetary award than normally given for intellectual chitchat. Barbara and Gordon were there in pursuit of Truman Capote. At the meeting, Gordon persuaded Capote to let Esquire, where he reigned as “Captain Fiction,” to serialize his newest opus, Answered Prayers. Before arriving at Palm Coast, we visited Disney World, where Duncan, just shy of his third birthday, screamed all through the jungle boat ride.
We were just a month settled into Airslie, its new picture windows alluringly draped with Swedish cloth we found in the D&D building on Third Avenue. Its many rooms let Liz invite her parents and her two brothers and sister, as well as her aunt from California and grandmother from Philadelphia, to spend Christmas day with us. But the big Christmas feast, preparation for which included many hours basting two geese, did not go as planned. By the time the fowl were on the dining table everyone except the schoolteacher aunt and physician dad had come down with twenty-four-hour retching flu. The night before, we had received all the families in Lab housing for warm Christmas grog. I didn't know whether they had brought the contagion or whether one of Liz's family members was its origin. Fortunately, there was no sign of a Boxing Day epidemic.
That year, the newly winterized Davenport Lab was utilized by three supermotivated yeast geneticists on sabbaticals: David Botstein from MIT, Gerry Fink from Cornell, and John Roth from the University of California at Berkeley.
After Christmas, our yeast trio and the tumor virologists began to discuss what should happen at Asilomar II, scheduled for February 1975.1 increasingly worried about restrictions that might be imposed on the use of recombinant DNA technologies to clone putative cancer-causing genes. In fact, these procedures would greatly reduce whatever risks we were now incurring using live SV40 virus or adenovirus 2. Our call for a moratorium, however, created the mistaken impression, magnified by each successive press conference, that working with recombinant DNA was a potential major public health hazard possibly equal to nuclear weapons. Even before the meeting started, Joe Sambrook had been asked to join fellow tumor virologists in coming up with guidelines that could only retard the development of recombinant DNA technology.
When I arrived at Asilomar, I found that virtually all the 140 participants were inclined toward accepting restrictions of one sort or another. Only Stanley Cohen, Joshua Lederberg, and I thought they were the wrong way to go. To no avail we voiced the impossibility of regulating an unquantifiable risk. Harm to someone or something had to be demonstrated before regulation could be rational, and to our knowledge no tumor virologist had come down with a cancer likely to have been caused by lab exposure. But for Paul Berg and his Asilomar II co-organizers, there seemed no way out of accepting some form of NIH-imposed guidelines. If we attendees did not accept them, the wrath of public opinion would surely descend upon all of us. And if we did not propose them they would be imposed upon us in more draconian form. At the meeting's end, virtually all participants warily voted to approve the mildly restrictive rules prepared by the several working groups. If the public found them satisfactory, recombinant DNA experimentation should not be too badly set back. On the small feeder plane taking participants back to the San Francisco airport, however, I was full of foreboding. I believed that trying to look good, as opposed to doing good, could only backfire.
A week after Asilomar I flew up to Boston to speak at the dedication of
MIT's Cancer Center. In my talk, I offered my view on how to fight the escalating “war on cancer.” I proposed that money would be best spent initially on creating centers filled with Ph.D.'s, as opposed to M.D.'s. I did not see the big clinical cancer centers then as having the potential to attract the very bright young scientists who could find the molecular essences of cancer. And without those molecular keys all the money in the world would only little improve what clinicians could do. Only after my speech did I learn that an inexperienced young stringer for the Washington Post had been in the audience. To my horror, the next day the Post ran his story over the headline “Nobelist Calls War on Cancer a Failure.” I immediately wrote Dick Rauscher, the RNA tumor virologist now heading the NCI, to say that I had been badly misquoted. Fortunately, someone on his staff, Phil Stansley, also heard my talk, and backed me up.
With my $1,000 MIT honorarium I soon acquired for the Lab a Milton Avery-like abstract painting by the talented Long Island artist Stan Brodsky. It gave real style to the fireplace room of Blackford Hall until it was damaged by a large spoon thrown during a summer banquet food fight. After repairs costing almost half the original purchase price, it went back on the same wall until the next food fight damaged it again. This time the harm was slight, and it was only a few days before its subtle red, pink, and blue colors could again be admired.
In the fall of 1975, I resumed teaching at Harvard, flying up to Boston to spend Sunday and Monday nights at the Harvard Faculty Club. My lectures on tumor virus and animal cells were updated versions of those I had given three years before, using as a text the Lab's monograph The Molecular Biology of Tumor Viruses. This was to be the last course I would teach at Harvard. Matt Meselson was unwilling to appeal to the dean for an exception to Harvard's long-standing prohibition against sharing faculty with other institutions. And so I was informed that, as of July 1,1976, I would no longer be a professor at Harvard. It was a situation of my own making, but all the same I was much annoyed, if not insulted, since Jack Strominger had recently become director of research at the Dana Färber Cancer Institute across the river while retaining his professorship in our department. Jack, moreover, now was being paid by both institutions, while I would have been content with only one salary if I could keep both jobs. There were many things I knew I would miss about Harvard, but by far the first would be its students; the obligation to lecture to them forced me to extend my own thinking, and occasionally the most extraordinary ones came down for research at Cold Spring Harbor, enriching the intellectual fellowship there.
Just after Christmas, I flew to the West Coast with Liz, Rufus, and Duncan for a two-week visit that started in southern California, where for a week we stayed in an apartment on California Avenue just west of Caltech. There Max Delbrück had arranged for me to give a lecture honoring the recently deceased Jean-Jacques Weigle. I had always enjoyed Jean's nimble brain both at Caltech and when visiting him in his hometown of Geneva, where he did phage experiments in the summer. Afterward we drove up to San Francisco, where W. A. Benjamin held a book party to mark the appearance of the third edition of The Molecular Biology of the Gene. Like the first and second editions, its sales over five years would approach a hundred thousand copies.
Then working at Cold Spring Harbor developing a powerful new way to clone genes was the thirty-two-year-old Tom Maniatis. His highly innovative experiments at Harvard as a postdoc with Mark Ptashne had led to his recent appointment as assistant professor. Initially he was to come to Cold Spring Harbor Laboratory for only a year for work, returning to Harvard upon its building of facilities for animal cell experimentation. In collaboration with Argiris Efstratiadis of Fotis Kafatos's Harvard lab, Tom was using messenger RNA molecules from red blood reticulocytes as templates to make full-length double-stranded DNA copies of the ß globin gene. No biohazard possibilities could arise from such experiments, so despite the recombinant DNA moratorium, Tom and his four young collaborators were able to move full steam ahead in their Demerec Laboratory space.
With Rufus (right) and Duncan in 1973
By then, his well-directed intelligence had also caught the attention of Caltech's biology department. Caltech let Tom know it was prepared to make him a tenured member of its faculty. Upon learning this, Mark Ptashne got BMB to ask Henry Rosovsky to move quickly in assembling an ad hoc committee and win approval to offer him a tenured associate professorship. In February I went back to Harvard to attest to Tom's accomplishments before Derek Bok. As expected, Tom was approved.
Resignation…
The worry for Harvard all too soon became the possibility that Tom might choose to accept Caltech's offer anyway. The ever more vocal in-house opposition to recombinant DNA experimentation within the Biological Laboratories was hardly an inducement to prefer Harvard. The newly appointed assistant professor Ursula Goodenough and George Wald's wife, Ruth Hubbard, also a scientist, were claiming recombinant DNA experimentation using E. coli might put the women in the Bio Labs at risk of cystitis. Both should have known that over the past ten years live E. coli cells had been regularly ground up by the pound by men and women alike without a single case of illness.
…and response
Initially Mark and Tom did not worry, knowing that Henry Rosovsky was not one to be intimidated by such nonsense, whose source was mainly left-wing elements that had been gaining ground on campus ever since the occupation of University Hall, and which after Vietnam had been further energized by Watergate. It did not matter to Rosovsky that at a public meeting in late May more students had been moved by the rhetoric of Richard Lewontin, Harvard's population geneticist, railing against future capitalistic exploitation of DNA research than had been stirred by my pleas to get on with cancer research using recombinant DNA. Henry Rosovsky sided with scientific progress and gave Harvard scientists the go-ahead to continue the controversial research. So Harvard's “science for the people” leaders took their case to the Cambridge City Hall and its populist mayor, Alfred Vellucci, always keen to put the Harvard elite in their place. At George Wald's urging, he and his fellow councilmen held hearings on June 27 and July 7, 1976, after which they voted for a three-month moratorium on recombinant DNA research within Cambridge city limits. Tom now felt going back to Harvard would be to enter a state of chaos, and so he accepted Caltech's offer, as feared.
Before reaching that decision, Tom had seen me very angered by Harvard for very different reasons when I appeared in his Cold Spring Harbor lab late in the evening directly following my return from several days in Cambridge. Derek Bok had invited me to his office in Massachusetts Hall, and I was expecting that Harvard would bid me farewell in some meaningful way. But for my presence at the Biological Laboratories for the past twenty years, its science would have commanded much less attention from the outside world. Wally Gilbert might very well still be a physicist, while Matt Meselson, and likely also Mark Ptashne, would be teaching in California. To my dismay, Derek's goodbye was entirely perfunctory, giving not a hint that my departure was any loss for Harvard or any detriment to its future.
At the start of June, I flew back to Boston for my last visit to University Hall as a member of its faculty. That afternoon, Henry Rosovsky and I tried hard not to focus on the fact that I was soon to be gone. It was easier to talk about George Wald's pretentious irresponsibility in opposing recombinant DNA. After twenty minutes of not wanting to say goodbye, I thanked Henry for trying so hard to get Harvard on the animal cell bandwagon. If I had not become irreversibly committed to Cold Spring Harbor, together we would have won. Realizing it was almost time for his next appointment, Henry, to my surprise, revealed that in looking over my salary history he noticed that I had always been paid too little. It was his way of saying he liked me. He and I knew that I would be sad walking out of Harvard Yard that day. Even I was not entirely immune to the old chestnut that there is no life after Harvard.
Remembered Lessons
1. Avoid boring people
Never make dull speeches that easily could
be delivered by someone else. Predictable words naturally compel audiences to tune out and lock their pocketbooks. Just as tedious is bringing small groups of busy people together for committee meetings with no opportunity for them to offer real input. This is on a par with holding meetings where talk is not followed by meaningful decisions. In both circumstances, committee members will likely soon stop attending gatherings they know will be a waste of their time. Not boring others, of course, requires that you take pains not to become boring, as often happens when you begin to bore yourself. A leader's mind must continually be reconfigured through exposure to new patterns of acting and thinking. Reading the same papers and magazines as everyone else around you is not likely to make you an interesting dinner guest, let alone alter your consciousness. In my case, a subscription to the Times Literary Supplement, courtesy of my father-in-law, made me more interesting to sit beside than someone whose diet was limited to Time, Newsweek, or the Economist—or Nature for that matter.
