Avoid Boring People: Lessons From a Life in Science (38 page)

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.