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ANNUAL REPORT 1981 COLD SPRING HARBOR LABORATORY Cold Spring Harbor Laboratory Box 100, Cold Spring Harbor, New York 11724 1981 Annual Report Editors: Annette Kirk, Elizabeth Ritcey Photo credits: 9, 12, Elizabeth Watson; 209, Korab, Ltd.; 238, Robert Belas; 248, Ed Tronolone. All otherphotos by Herb Parsons. Front and back covers: Sammis Hall, new residence facility at the Banbury Conference Center.Photos by K orab, Ltd. COLD SPRING HARBOR LABORATORY COLD SPRING HARBOR, LONG ISLAND, NEW YORK OFFICERS OF THE CORPORATION Walter H. Page, Chairman Dr. Bayard Clarkson, Vice-Chairman Dr. Norton D. Zinder, Secretary Robert L. Cummings, Treasurer Roderick H. Cushman, Assistant Treasurer Dr. James D. Watson, Director William R. Udry, Administrative Director BOARD OF TRUSTEES Institutional Trustees Individual Trustees Albert Einstein College of Medicine John F. Carr Dr. Matthew Scharff Emilio G. Collado Robert L. Cummings Columbia University Roderick H. Cushman Dr. Charles Cantor Walter N. Frank, Jr. John P. Humes Duke Mary Lindsay Dr. Robert Webster Walter H. Page William S. Robertson Long Island Biological Association Mrs. Franz Schneider Edward Pulling Alexander C. Tomlinson Dr. James D. Watson Massachusetts Institute of Technology Dr. Boris Magasanik Honorary Trustees Memorial Sloan-Kettering Cancer Center Dr. Bayard Clarkson Dr. Harry Eagle Dr. H. Bentley Glass New York University Medical Center Dr. Alexander Hollaender Dr. Claudio Basilico The Rockefeller University Dr. Norton D. Zinder State University of New York, Stony Brook Dr. Thomas E. Shenk University of Wisconsin Dr. Masayasu Nomura Wawepex Society Bache Bleeker Yale University Dr. Charles F. Stevens Officers and trustees are as of December 31, 1981 DIRECTOR'S REPORT 1981 The daily lives of scientists are much less filled now be solvable or whether we must await the re- with clever new ideas than the public must im- ception of some new facts that as yet do not exist. agine. To be sure, we have largely been educated Here we generally think ahead for a period of one with the best thoughts of the past, but as we all to several years, knowing we are likely to lose our learn in school, the reading of history does not letgrants or potential for further fellowships if we us predict the future. It is not that we are muchshow no progress. Even more important, failure too satisfied with the earlier triumphs of ouritself is not pleasant to live with, and our very youths. Even the most profound leaps forward be-sanity is likely to demand a move to a more realis- come boring if lectured on too often. I remembertic objective. that after giving only some six lectures on the dou- The question thus should be asked asto ble helix, I had gone stale and desperately neededwhether this past decade's massive preoccupation some new thought to emerge so as to regain thewith the nature of cancer cells was premature feeling of being alive. But wanting to be clevergiven that even today we know so little about nor- and achieving it are not the same. During thosemal cells. Most fortunately, we had not bitten off post-DNA semi-blues, I had moved to Caltech and more than we could chew. Our apparent gamble become friendly with Dick Feynmann, then thein pushing such large masses of federal monies in- brightest star on its or any other physics scene.to research on cancer, as opposed to, say, into de- Then he liked to tell others how hard it was forvelopmental biology, was never that far out a bet. him to develop a first-rate idea and that nothingFor already by the early 1960s unambiguous con- of value had come easily. There was always the nections between cancer and many different vi- possibility that Dick was exaggerating his strug- ruses had been established. It was not that viruses gles, to make those of us less intellectually en-were then thought to be the cause of most cancer. dowed more at ease with his brilliance. It seemedWhat we liked best about them was that they wisest, however, to take his words at face value.were the perfect tools to probe the molecular Success would not necessarily come with hardgenetics of higher vertebrate cells. Viruses gave work, but without its pain true advances wereus a logical handle to use our brains, as opposed unlikely to fall out. In the now almost 30 yearsto our emotions, in deciding what to do next. that have since elapsed, I have seen almost no ex- I first became aware of the possibility of using ceptions to this generalization and find that I viruses to study cancer in the fall of 1947 when, as quickly lose interest in a scientist ifI discover thata beginning graduate student at Indiana Universi- he lacks virtual monomaniacal interestinhis ty,I took Salva Luria's course on viruses. Not until work. 1959, however, did I see any way to rationally Most of our days are thus spent not being cleverconnect viruses and cancer. Then I first learned of about the future, but somehow hopefully posi-Seymour Cohen's recent research showing that tioning ourselves so as to be thought clever atthe DNA molecules of the T-even bacteriophages some later period. To start with we must knowcoded for proteins involved in DNA synthesis. what we want to solve. If we start out to conquerThis discovery opened my mind to the possibility a minor goal, then the odds are hopelessly stack-that animal viruses might have similar genes, and ed against us. On the other hand, if we set oursoon I was telling everyone within reach that the sights on an important objective merely becausecancer-causing (oncogenic) capacity of the DNA it is there, we should not assume that its intrinsictumor viruses must arise through their possession importance in any way justifies inevitable failure.of genes that turn on DNA synthesis. But my idea We all know too many people who have set out tofailed to excite anyone else, in large part because crack the mysteries of the human brain and havethere was no way to test it. After a politely cool only invented new words to describe our continu-reception before a large audience at Massachu- ing deep ignorance of perception, memory, andsetts General Hospital, I returned to thinking learning. It is therefore essential to gain somehowabout protein synthesis. This was a wise move. In a feeling as to whether a given problem mightcontrast to cancer, there were hard facts to think 5 about, and we would soon be searching success- their functions was now feasible given sufficient fully for messenger RNA. funding. Soon afterwards, the exciting molecular nature In retrospect,I was far more optimistic than I of the newly discovered DNA tumor viruses, poly- should have been given the hard facts at my dis- oma and SV40, became known. They were among posal. Even then, almost 20 years after the dis- the smallest of any known viruses, having virtual- covery of the double helix, our tools for directly ly no more genetic information than the smallest analyzing DNA were primitive, with most of our bacteriophages. And they could be propagated in past successes with E. co/i the result of sophisti- cells growing in culture, thereby allowing the rou- cated genetic analyses that we saw little chance tine preparation of radioactively labeled virus. of soon duplicating with higher cells like those of Moreover, through the work of Dulbecco, Stoker, the mouse or humans. On the other hand, I knew and Sachs these tiny tumor viruses were shown to well that a rash of unexpected new discoveries be capable of converting cultured normal cells in- had allowed the genetic code to be elucidated to their cancerous ("transformed") equivalents. much sooner than any of us thought possible The stage was thus set to test directly whether the when we took on this objective after the dis- transformed cells contained new genetic informa- covery of the double helix. And so I hoped that tionacquired fromtheirrespectiveinducing during the 1970s many powerful new experimen- tumor viruses. These crucial experiments, first tal procedures would become availableif our done (1965-1968) in Dulbecco's lab at the Salk science continued to be well-funded. Institute,revealedthepresenceof polyoma But at first the SV40 work here, as in the other (SV40)-specific DNA (genes) within the trans- labs that had gone into the DNA tumor virus field, formed cells. There they had become inserted in as expected went painfully slowly. Wisely, we did the host-cell chromosomal DNA and most likely not ask ourselves too often where we were likely coded for cancer-inducing proteins. to have real answers that might excite us, much By this time (the late 1960s) the basic features less others. Then, almost without warning, the of the genetic code had been worked out, and restriction enzymes of Werner Arber were realiz- with the isolation of the first bacterial repressors ed to be the almost magical sequence-specific there was a widespread feeling among molecular DNA-cutting enzymes that we had so long dreamt biologists that the moment had arrived to tackle about but never seriously thought would exist. the structure and functioning of higher eucaryotic And happily there turned out to be many, many genes. And given that the most successful route cutting enzymes, with Richard Roberts here quick- into the genetic essence of E. coil had been ly changing the face of DNA chemistry through through its viruses, the phages, the most sensible his isolation, from a wide variety of bacteria, en- way to approach the vastly more genetically com- zymes that cut at a very large number of unique plex higher eucaryotic cells had to be through in- DNA sequences.