What mattered most then were the phage facts and ideas, not the individuals who brought them forth. This was Max's biggest impact on the phage group and it allowed us to take real joy in the discoveries of others instead of being jealous of them for providing our intellectual excitement of the moment. In retrospect, Max's unchallenged scientific collectivism was helped by the still so-mysterious nature of the gene. It was not then clear what types of phage experiments could lead to a real breakthrough, and no two individuals were pursuing the same experimental approaches. Only with the 1952 Hershey-Chase experiment did the primacy of DNA became clear The discovery a year later of its double helical structure started us thinking about how genetic information is encoded by the sequences of base pairs. The ways to pin down how DNA functions in protein synthesis, however, long remained partly clouded. So for the next 15 years, we remained in the happy situation where there were more important problems to solve than scientists opting for their challenges.

By then I was on the Harvard faculty, and it was easy to propose potentially important thesis topics for my students without worrying whether someone else would be doing similar experiments. Just one of my students had his thesis work made largely irrelevant by more incisive findings elsewhere, and only once, when searching for the molecular nature of nonsense suppressors, did we consciously find ourselves racing against another lab. Happily we won that race when, in 1965, Mario Cappechi and Gary Gussin found mutant tRNAs to be the molecular entities that misread nonsense codons as sense. In retrospect, the pace of research up through the end of the 1960s was not that hurried, and summers could still be used as low-key periods for recharging our intellectual batteries. Life at Cold Spring Harbor correspondingly remained much as when I first came here, with the students taking the summer courses occasionally bringing along wives, if not families, and regulars like Rollin Hotchkiss coming each year for the occasional summer experiment in Jones lab.

After I became Director of the Laboratory in February 1968, I brought here for the coming summer some of the better of the younger scientists working on phage l. At that time, my Harvard lab was increasingly focused on this most fascinating lysogenic phage and I saw great advantage in having my so-oriented students come in long contact with their peers from elsewhere. Max and Manny were once again regular summer visitors, with Max, at John Cairns' urging, having started in 1965 a workshop on Phycomyces, the mold then used as a model system for studying biological responses to light. Each summer, the Delbrücks were domiciled in the utilitarian Page Motel. Perfect for outside-oriented visitors, it easily allowed Max and Manny to assemble friends on the lawn outside for barbecues. I had just married Liz, and Max and Manny, knowing that all too many young scientists are not people-oriented, graciously made her welcome in their homeaway-from-home. The Delbrücks were to return for five more workshops between 1971 and 1976, by which time Max was 70 and saw the need for others to assume leadership of Phycomyces research.

During the early 1970s, improving Laboratory finances allowed us to install heating systems and modernize many of our run-down older buildings that were formerly relegated to summer activities. Cold Spring Harbor as a summer-dominated institution began to vanish as we strove to become one of the world's more exciting sites for tumor virus research. In particular, by focusing on the small DNA tumor viruses SV40 and adenovirus, we hoped to identify genes that make cells cancerous. Initially, our tumor virus lab, led by Joe Sambrook, had almost the aura of a tiny frontier mining encampment filled with upstarts waiting to take big risks. Each was hoping that their next experiment would lead to a gold strike. In so prospecting, they needed brains and brawn as well as luck. Those not of strong will and guts knew they were out of place and moved elsewhere. On Friday nights, our Blackford Hall bar had the swagger of a western saloon awaiting the inevitable gun fights that would come during our impending tumor virus meetings. Certain personalities were bound to prove more than others could bear.

These tensions, so ready to explode, were still those of the academics searching primarily for intellectual glory. The academic powers to be won were likely to be marked by family cars bearing no more cachet than a Chevrolet. No one here then thought he might soon have facts or ideas about cancer cells that would have commercial applications. Like most pure academic biologists, we looked more with disdain than envy on those chemist acquaintances whose industrial contacts let them live in homes almost suitable for bankers. So with sufficient monies coming from the War on Cancer to support our experiments, I saw no reason to taint our reputation for academic purity by unnecessarily promoting commercial activities. With no hesitation I turned down Richard Roberts' request that our Lab help start a company to commercialize the new restriction enzymes that he was isolating. For several years, he had been providing them gratis to scientist acquaintances, but now he was receiving more requests than he could handle.

The rough saloon camaraderie of tumor virology research persisted through our 1979 Viral Oncogenes Symposium. Its record-breaking 141 presentations allowed virtually everyone with a true result to speak up and be heard. Then, as the powerful new procedures of recombinant DNA became available, key objectives became much easier to reach and our cowboy era was over. Once one mastered the new gene cloning procedures, experimental success was almost foreordained. So oncogenes quickly moved from being largely hypothetical constructs to definitive DNA sequences. Correspondingly, which experiments to do next became more obvious, with the road maps to reach key objectives often available to all. Lab sizes had to grow to keep others from mining important quarries that in the past were treated as personal possessions. Summer became no different from any other time of year, and once a tumor virus meeting was over, its participants quickly departed back to their labs.

In the early 1980s, tumor virology moved beyond the concept of oncogenes to embrace the equally important concept of tumor suppressors. These were genes whose loss could also lead to the cancerous phenotype. Oncogenes became seen as the accelerators of cell growth and division, whereas tumor suppressor genes were perceived as the corresponding brakes. It was here at Cold Spring Harbor that these two means of cancer causation first effectively came together. In our new Sambrook Lab, Ed Harlow made his seminal 1988 finding that the E1A oncogene of adenoviruses acted by neutralizing the key cellular tumor suppressor Rb protein. Through this watershed observation, we at last knew how to go after the molecular mechanisms by which the various forms of human cancer arise, either by oncogene acquisitions or by tumor suppressor gene losses. Immediately, we foresaw a rapidly escalating pace of cancer research, since the number of human oncogenes and human tumor suppressor genes was likely to be large.

In our current search for the vast multiplicity of genetic changes that underlie human cancer, the social fabric under which we work bears little relation to the cowboy days of the 1970s. Virtually all of our research objectives have human implications, and we must increasingly face the fact that our scientific competitors are now located in commercially based, as well as academic, institutions. In a real sense we should be happy, because this now means that those financial types who control big sums of money believe that soon there will be real payoffs from our cancer research. On their horizons are scores of new diagnostic tests as well as the successful utilization of cancer-gene-derived molecular targets for the generation of powerful new classes of anti-cancer drugs.

Now that commercial, as well as academic, gold lies within our potential grasp, past ways to achieve socially acceptable balances between competition and cooperation among scientists will be even harder to maintain. Our scientists will see the need not only to publish first, but also to be the first to file concomitant patent applications. In the past, scientific civility was greatly helped by individuals deciding to publish simultaneously even though one group might have been one to two months ahead in reaching the main conclusion. Unfortunately, patent law does not forgive being a few days late and the winner gets all.

For the foreseeable future, research sweat, as opposed to research fun, will thus increasingly dominate the day-to-day atmosphere of cancer research. We should not, however, moan too long for our past days of academic purity. Instead, we must accept our frenzied states as manifestations of our increasing scientific optimism that the splendid science of the past 30 years will soon lead to reduced feelings of dread when the physician's verdict is "cancer." But for us as academics to continue as vital forces in cancer research, we will necessarily have to act more and more like our more commercial compatriots. Expensive new genome technologies, for example, must not remain restricted to big pharmaceutical laboratories or well-capitalized biotech firms. Instead, they must become available to the academic community. Luckily, this is a year when federal funding for cancer research may greatly increase. If it is deployed well, academics such as ourselves can continue to be major players in turning cancer knowledge into cancer cures.

In so working to remain an important player in cancer research, we must also see to it that Cold Spring Harbor Laboratory retains its cherished role in the broader world of biology and medicine. We must remain an institution primarily focused on the generation and dissemination of ideas as opposed to their commercial exploitation. One way to so continue is to strengthen even further our advanced teaching programs. Now we offer 25 courses in contrast to just one in 1945, when Max Delbrück taught the first phage course. But to keep our courses first-rate, we must constantly improve their laboratory facilities and equipment. Now, for example, only seven years after completion of our Beckman Lab, its teaching facilities are inadequate for teaching the new nerve cell imaging techniques. So we have just started construction of our new Edwin and Nancy Marks Imaging Building, with its completion anticipated as the new millennium starts.

We will always need warm and wise friends, like the Marks, who come to our aid when we need to move forward quickly. Manny Delbrück long helped us in this way. Soon after I became Director, she provided the funds that allowed us to transform the then-derelict Wawepex Laboratory into new dormitory space. In this way we were able to house the students for the new neurobiology courses to be given in newly renovated teaching space in McClintock Laboratory. Manny's help also made possible the new tennis courts on Bungtown Road on the way to the sand spit. Sadly, upon her death early this January, we have lost our last close connection to the first heroic period of phage research. Now, however, we should not weep too long for Manny but instead rejoice that she was so long a part of our lives. In the same way, we must not dwell too much on our loss of the former coziness of those Cold Spring Harbor summers that witnessed the coming of the phage world.

There will always exist those individuals who, like the early pioneers of the phage world or tumor virology, feel happiest in moving upon uncharted water. Today, the way precise information is stored in and retrieved from the human brain appears equally, if not more, mysterious than the necessarily fuzzy way I perceived the storing of genetic information during my first Cold Spring Harbor experience some 50 years ago. Small groups of young scientists, attracted by the prospect of not following their elders' paths, are bound to assemble again to meet this challenge.

As long as we remain a home for tough risk-takers, not caring too much whether or not there might be gunslingers among them, we should not worry too much about how the start of the forthcoming millennium will find us.