by James Watson
That summer, Cold Spring Harbor Laboratory published Experiments in Molecular Genetics, a much expanded version of material taught by Jeffrey Miller two years before in our annual bacterial genetics course. Its intellectual sparkle and visual elegance would likely lead to its wide adoption and thus real money for the Lab. It was a bargain—maybe too much of one: more than 450 pages for only $11.95. Like Jeffrey and all our other authors, I also then wrote gratis for the Lab. At roughly the same time, I was about to finish two long introductory chapters for the Molecular Biology of Tumor Viruses. When first conceived, it was to be a short book. But it steadily grew to more than 750 pages in thirteen chapters, written by twenty-two authors who included David Baltimore and Howard Temin, who were to share the 1975 Nobel Prize for their research on retroviruses. Also writing much of the book was Joe Sambrook, whose great talents as a scientist I found equaled by his ability to produce succinct, readable prose as well as edit the lesser sentences of others, myself included. He refused, however, to share credit as one of the editors. The book spine later showed only the name of my former Harvard postdoc, John Tooze, then in central London helping Michael Stoker run the Imperial Cancer Research Fund Laboratory bordering on Lincoln's Inn Fields.
The Lab's next book was the small volume Biohazards, drawn from the proceedings of a meeting held in January 1973 at the Asilomar Conference Center near Monterey, California. Its three days of discussions were organized to codify lab procedures appropriate for working with tumor viruses. No consensus emerged, however, among the one hundred attendees as to what precautions, if any, should be taken.
Helping to organize the meeting as well as to edit the book was our recently appointed staff member Bob Pollack, continuing research on SV40-transformed cells that he began at New York University Medical School. Originally a physicist, Bob had anxieties like those of Charlie Thomas about the safety of tumor virus research. I sometimes shared those worries, and as a precaution discontinued positive air pressure in our James virus labs. Positive air pressure was widely used in microbiology, a relatively higher pressure in the room preventing microbial contaminants in the outside air from entering. By the time of the meeting we had put these rooms under negative pressure, with their air venting through HEPA niters to keep viruses from escaping into the outside air.
Of increasing concern to me then was the possible doubling in size of the fifty-slip Whaler's Cove Marina on the eastern shore of the inner harbor. As it was, it posed no real aesthetic threat to the tran-quility of our waterfront. But it had been purchased two years earlier by Arthur Knutson, principal owner of the larger marina operations in nearby Huntington Harbor, who shortly thereafter proposed to use the adjacent Captain White House to expand the local yacht club. This would turn Cold Spring Harbor into a very busy port indeed. Though neighbors had legally challenged Knutson's proposal, we were advised they were likely to lose. If our harbor was to be saved, the Lab somehow had to buy the marina.
Our able administrative director, Bill Udry, recruited Jerome Ambro, supervisor of the Town of Huntington, to help us. His intervention was critical since the town of Cold Spring Harbor did not exist as a legal entity—the eastern shore of the inner harbor was actually a part of Huntington. Bill and Jerry came to lunch at Osterhout, where we looked out on the marina while enjoying Liz's poached oysters. I was never privy to how Ambro subsequently persuaded Arthur Knutson to sell us the Whaler's Cove site. It was too bad, I thought, the Lab did not have means then also to buy the sea captain's handsome house.
The Board of Trustees approved the purchase early in June, just a week after the Robertson Research Fund formally came into existence. But their concordance was not as routine as expected. Arguing against the acquisition was our nearby neighbor Walter Page. Long an important Lab friend and a trustee during John Cairns's first years as director, Walter had left the board when the Morgan Bank sent him to London for several years to run their European operations. Upon his return, we asked him to rejoin the Board, but he begged off, citing his growing Morgan responsibilities. But when Charlie Robertson became our benefactor, Walter knew he had to come back to make sure our new riches would not be squandered. Spending $300,000 to buy a marina was not Walter's idea of a prudent first expenditure. I, however, believed that not to make the purchase was surely to waste perhaps our only chance to forever preserve the inner harbor's pristine state. An ideal setting for science is not a matter of purely utilitarian considerations. Sensing our fellow trustees swaying in Walter's direction, however, I threw a Hail Mary pass, threatening to resign if the marina was not purchased. After I made my announcement, I left the James seminar room and walked back to Osterhout Cottage, about a minute away.
There Liz was entertaining Marilyn Zinder, whose husband, Norton, was attending the Trustees meeting. I announced my abrupt move, and we nervously waited some forty-five minutes until Bentley Glass came in to say that the trustees had just voted to purchase Whaler's Cove. I walked back with him to the meeting, rather sheepish at having got my way by reason of blackmail. I would never again challenge Walter, against whom one public victory was one too many. As Cold Spring Harbor's most respected resident and an old friend of the Lab, he should have been informed well in advance of the meeting of how strongly I felt. Harvard duties that spring, however, had kept Liz and me largely in Cambridge. There we were comfortably ensconced in a Harvard-owned Kirkland Place house, less than three hundred feet from Paul Doty's much bigger mansard-roofed mansion. It had become our Cambridge residence in the fall of 1971, giving us plenty of space in which to prepare for the impending birth of our son Duncan early in 1972.
I no longer had John Cairns to help me bat around the pros and cons of impending Lab decisions. In early March, he returned to England to take the directorship of Mill Hill Laboratory of the Imperial Cancer Research Fund. The previous four years, his position at Cold Spring Harbor had been happily stabilized and paid for by an American Cancer Society professorship. Soon after getting it, John threw a big wrench into the science of Arthur Kornberg by finding an E. coli mutant able to live without his famous enzyme DNA polymerase. Its existence soon led to several successive searches for alternative DNA polymerases. Without John's genetic approach, the inherent complexity of DNA replication would have remained unknown much longer.
The Cairns family's departure opened up the possibility of my family occupying Airslie, the large rambling wooden structure that had housed the Lab's directors for almost thirty years. Built in 1806 for Major William Jones, Airslie had come into the Lab's possession upon the wartime dissolution of the late Henry deForest's large estate to the immediate north along Bungtown Road. Before Liz and the children and I moved in, however, we undertook a badly needed massive renovation. The Lab had previously never had funds for anything except the occasional fresh coat of paint and, once, a new roof. Cold winter winds blew through Airslie during all the years of Demerec's and Cairns's occupancy.
An initial plan drawn up by a New York architect seemed wrong at first sight. He would have given Airslie a formal Federal style appropriate for rich New England merchants. Somehow we had to find an imaginative designer to give the place its own character. Luckily I had just read that the celebrated Yale architect Charles Moore was doing a low-cost housing project in nearby Huntington Station. The year before, staying in the “honeymoon suite” of Sea Ranch, the resort he created above San Francisco, Liz and I had much admired the daring of its multiple sloping roofs. I arranged for Moore's next visit to Long Island to include a brief visit with us. A week later, Liz and I were observing up close his playful mind reimagining Airslie.
Luckily Moore's plan was within the Lab's fiscal reach. Less than a month passed before we saw his final scheme while he was up at Harvard lecturing to architecture students. We were immediately taken with the way he opened up the front of the house into a three-story hall, giving Airslie for the first time a large central staircase. On our next visit down to Cold Spring Harbor I shared the plan with the trustees,
a little apprehensive imagining what they might make of the bold way Moore created large, open spaces from tight, smaller rooms. In particular, I worried what our new chairman and nearby neighbor, Bob Olney, would think. Happily, Bob approved, provided the local preservation society didn't object. On their subsequent visit, the society's president declared that Airslie lacked any design features worth preserving. His only concern was with saving some ancient panes of glass. Though it was rather impractical, we resolved to keep the small 150-year-old glass pieces that ran along both sides of the front door. And so early in the fall of 1973, when Airslie was no longer needed for overflow summer housing, the fourteen-month project started. The final cost of just under $200,000 seemed embarrassingly extravagant for housing the director. Once we moved in, we realized that Moore's unique design gave Liz and me a way of life usually enjoyed only by the very wealthy. But it occurred to me that one day this would help us lure my successor; contrary to stereotype, most scientists are far from indifferent to the finer things in life.
The following year, Robertson Research Fund money let us readapt Jones Laboratory into a year-round neurobiology facility. Charles Moore and his highly talented young coworker Bill Grover imaginatively placed the four specialized neurobiology modules as freestanding aluminum-covered boxes accented by boldly colored wooden strips. Charles Robertson and his new wife, Jane, came to its dedication ceremonies. Earlier in the summer, the Robertsons had invited all the speakers at the June symposium on the synapse for a late afternoon party. It marked our gracious host's last year in the home he had so lovingly occupied for almost forty years. By then he had given up plans to build a modest summer home next door to our proposed conference center, accepting that his and Jane's future would be mainly spent in Florida at his large waterfront estate in Delray Beach.
Even before Airslie was gutted and the electricity turned off, Liz and I wondered whether it soon might be our year-round home. How long Harvard would continue to let me be away so much was not yet settied.
Living in two places, moreover, would become less practical once Rufus reached kindergarten age. Early in 1973-74 I informed Harvard that I might move out of Kirkland Place when my spring term responsibilities ended. Many of its furnishings would go to Airslie and others to the house we had just bought on Martha's Vineyard.
I had wanted a summer home on the Seven Gates Farm on Martha's Vineyard since becoming aware more than a decade before of its thousand-acre vastness, on which corn was still grown. I knew several of the farm's civilized summer denizens very well, including our Cold Spring Harbor neighbor Amyas Ames, former chairman of Lincoln Center, who had presided over LIBA in the last year of Milislav Demerec's directorship. Owning one of its only thirty houses, however, seemed beyond my means until late August, when a Vineyard Haven real estate agent took us to a simple early-nineteenth-century farmhouse just put up for sale by a man about to retire to low-tax New Hampshire. Were we to sell the house on Brown Street in Cambridge, bought using my Nobel Prize monies, we could just cover the purchase price. The idea became irresistible once we imagined ourselves basking in the shade of the two magnificent American elms overhanging the wide farmhouse lawn. Equally important, only five miles away was Ed and Lucy Pulling's West Chop beachfront summerhouse.
From 1971 to 1973, my main teaching responsibility was a yearlong introductory undergraduate course on biochemistry and molecular biology (Biochemistry 10). In preparing for a spring 1972 lecture on DNA replication, I saw the need to point out the commonly accepted 5'→3’ DNA chain elongation mechanism led to incomplete double helices with single-stranded tails. Some molecular mechanism had to prevent DNA molecules growing ever shorter during each round of replication. Until then, no one understood why identical, redundant DNA sequences were found at the two ends of all linear phage DNA molecules. Suddenly I knew why. Redundant ends allowed right and left single-stranded DNA tails to hydrogen-bond to each other to form dimers. Further cycles of DNA replication would lead to ever longer phage DNA molecules. No longer mysterious to me was why replicating phage DNA molecules are many times the length of infecting phage DNA molecules. Excited by my brainstorm, I told it to my Biochem 10 students and, afterward, wrote it up for an article in an October 1972 issue of Nature.
Salvador Luria, Nancy Hopkins, and David Baltimore at the MIT Cancer Center in 1973
Soon my main concern at Harvard turned to making the Biological Laboratories another major site for tumor virus research; after coming strong into the molecular age, Harvard was risking again being behind the curve. In April 1973, however, the National Cancer Institute turned down Harvard's application for construction monies for animal cell facilities. The proposal's reviewers were not convinced that the building addition would be used in a way that well served NCI's mission. True enough, given my Cold Spring Harbor responsibilities, I would likely never directly oversee a tumor virus lab in Cambridge. Nor was it clear whether Mark Ptashne would abandon gene regulation in bacteria to work on retroviruses. And Klaus Weber might go back to Germany were he offered a high-level appointment. In contrast, MIT's application for NCI construction funds was approved without a hitch.
Actually, it was a shoo-in with David Baltimore and Salvador Luria as its main drivers. Soon they would conscript two Cold Spring Harbor initiates into tumor virus research: Nancy Hopkins, after two years in Bob Pollock's lab, and Phil Sharp, after three highly productive years in James Lab.
Moving much too slowly were the joint efforts of the Biology Department and BMB to recruit a tenure-level RNA retrovirologist. Though discussions began in the fall of 1972, letters seeking advice from eleven referees did not go out until six months later, in February. The referees were asked to compare as candidates Mike Bishop, Peter Duesberg, Howard Temin, Peter Vogt, and Robin Weiss. Temin's name was high on most lists, although with the caveat that he was not a consistently good lecturer. Two respondents advised that we also consider Harold Varmus. Mike Bishop was not on top of any list except for Bob Huebner's, who called him a highly intelligent biochemist as well as a lucid teacher.
On July 10, 1973, I went to University Hall to see the economist Henry Rosovsky, who had just replaced his fellow economist John Dunlop as dean of the Faculty of Arts and Sciences. Dunlop had hurriedly taken on the role during the April 1969 University Hall occupation when Franklin Ford suffered a mild stroke. I was then BMB's new chairman, a task I was to have only until February 1975, when Matt Meselson replaced me. During my brief tenure, I wanted to ensure that Harvard somehow acquired animal cell facilities equal to those MIT would have in eighteen months. That morning with Rosovsky, I stressed how important it was for him to ensure Klaus Weber's return to Harvard, a commitment Klaus could not make until up-to-date animal cell facilities were available in the Biological Laboratories or, better still, in the proposed new animal cell annex. Six weeks later, I took Klaus to Henry's offices to give Henry personal assurance that Klaus would come back to Cambridge if he could continue the experiments he and Mary Osborn had started at Cold Spring Harbor. By then Harvard decided to resubmit its application to NCI for construction monies, now opting for a completely separate new building on roughly the same site proposed for the annex. Several of the Biology Department faculty had become queasy about living with possible biohazards in their midst.
Harvard's president, Derek Bok, became actively involved on November n when the ad hoc committee met to consider whether Howard Temin should be offered tenure. I appeared as an early witness, sensing there would be no objection. Soon the question became whether he would agree to come. To answer it, he and his wife came to visit Harvard in mid-December. Their main host was Matt Meselson, a close friend of Howard's since their days together at Caltech in the late 1950s. I was worried from the start that his population geneticist wife, Rayla, would not want to leave the University of Wisconsin at Madison. Matt, however, thought we had a good chance of getting them to join us.
In January 1974, Henry Rosovsky scheduled a day to hear everyone out about
the proposed NCI grant resubmission. Carroll Williams expressed concern that receipt of NCI monies would force Harvard to use all of the government-financed space for work with cultured animal cells and their viruses. If the federal funds came forth, he thought BMB should relinquish some of its space in the Biolabs to let the Cellular and Developmental Biology subdepartment increase its numbers. In contrast, I argued for Harvard's quickly recruiting several animal cell hotshots who would create a high-powered cancer center like the one at MIT. It was my belief that all outstanding research on animal cells would easily fall within the purview of the NCI mission. Until we understood how cells sent out and received molecular signals to divide, we could not get at the essence of cancer, and understanding the mechanism was plenty to keep an animal cell group busy. I then told Henry the building would function best with a director reporting directly to the dean, which Carroll Williams resisted, seeing it would diminish the power of department chairmen. But I felt the chair's usual three-year term did not allow him or her to take on necessary long-term funding objectives.
The animal cell building proposal went to NCI in January just ahead of the deadline. The cover letter, signed by Derek Bok, was essentially written by me, with the requested construction money adjusted to $5.76 million, reflecting our architect's prediction of further inflation, which was then bedeviling the entire American economy. In its final form, the proposal was my vision—not Carroll Williams's—of how animal cell science should proceed at Harvard. But its realization much depended upon whether Howard Temin joined our faculty. More than a month of uncertainty passed before Howard finally turned us down, saying his wife saw her life diminished by moving to Harvard. No job she might find in Boston would be as good as the one she had with the population geneticist Jim Crow in Madison. To keep our NCI application alive, an offer was made to the English retrovirologist Robin Weiss. But soon he turned us down, as he had MIT the year before. My dominos continued to fall when Klaus Weber in early April formally accepted an offer to head a Max Planck Institute in Göttingen, Germany. It would provide even better facilities than could be fixed up for him within the confines of the Bio-labs. Harvard then had no choice but to tell NCI it no longer could claim a future in tumor viruses.
