Avoid Boring People: Lessons From a Life in Science (18 page)

Since my research achievements were already internationally noted and no one could say that I had either shirked or botched my teaching responsibilities, Paul Doty felt that fairness dictated that the Biology Department now also make up its mind as to whether it wanted me as a permanent member. Bundy happily agreed and unilaterally informed the Biology Department that he and Mr. Pusey wished to consider my appointment as well as that of Ed Wilson. With Wilson's offer from Stanford needing an answer soon, an ad hoc committee was formed even before a department vote, just before my thirtieth birthday on April 6. Through one of its members, the highly perceptive Rockefeller Foundation science executive Warren Weaver, Paul quickly learned that the verdict was thumbs up for both of us. By then Bundy had already told the Biology Department that he had President Pusey's permission to promote me as well as Wilson. So Frank Carpenter assembled his senior biology professors the next day to see whether they would concur with the ad hoc committee's decision.

I was more than worried that one too many of those dinosaurs would vote against me. In fact, a majority of them did, opting to postpone for one year the decision on my promotion. This I heard from Ernst Mayr, who wisely didn't identify those against me, and I couldn't contain my outrage. Retreating to the Doty house before I used the F-word in front of too many biology graduate students, I agitatedly awaited dinner with Paul and the Berkeley zoologist Dan Mazia. Over dinner Dan tried to console me by saying that at Berkeley they never would have tried to stave off what was so obviously inevitable. Paul Doty, trying to rescue his dinner party from the pall hanging over it, reassured me that the game was not over until it was over. McGeorge Bundy's power would be badly eroded if he let one of his second-rate departments defy him. Paul counseled me to try to refrain, at least for the time being, from further vulgar diatribes against my biology colleagues.

The subsequent weekend was inevitably tense, as I waited to see the color of the smoke emerging from University Hall. To my great relief, Bundy did play hardball, telling Frank Carpenter that no more tenured appointments or discretionary funds at the dean's disposal would go biology's way until they promoted me. Quickly those professors who only several days earlier were strongly opposed to me now implied they had acted too hastily. Upon further reflection they could now enthusiastically accept the ad hoc committee's recommendation.

Relieved not to have to consider offering myself to the Chemistry Department, I couldn't find it in me to gloat. But it was hard not to appreciate Seymour Benzer's later comment that the imbroglio attending my promotion made him even more certain that he had done the right thing turning down Harvard. Life was too short to share a department with so many prima donnas whose meager accomplishments scarcely justified even the status of has-been. Still, I did not regret moving to Harvard. More and more I was learning that the quality of your students matters much more than that of your faculty colleagues. In that regard Harvard couldn't be faulted.

    Remembered Lessons

1. Bring your research into your lectures

In the fall of 1956, there was simply not enough known about DNA to organize a whole course around it. So I opted to talk about DNA in the context of a course on viruses, wherein I could compare the elegant experiments of the phage group with the old-fashioned approaches of plant and animal virologists. Graduate students self-selected according to their attraction to my molecular messages. Reading through their term papers, I could also spot those who zoomed in on important issues and did not waste pages of type on observations of no consequence.

2. Challenge your students’ abilities to move beyond facts

Asking bright students to merely regurgitate the facts or ideas of others does not prepare them for the world outside classrooms. So my exams increasingly featured questions that assessed the plausibility of hypothetical headlines from the
New York Times
or
Nature.
For example, should they believe claims that a virus had been found that multiplied outside cells in a medium solely composed of the small-molecule precursors to DNA, RNA, and protein? Any student answering yes would have missed the essence of my course and so been advised not to choose a scientific career. Happily, no students failed to answer correctly.

3. Have your students master subjects outside your expertise

The best way to prepare your students for the independence they all want is by seeing that they are exposed to peripheral disciplines and to the technologies needed to move from the present to the future. During the late 1950s when we aimed to discover how information encoded within DNA molecules is expressed in cells, the answers had to be sought at the molecular level. So it was a no-brainer that I should have my prospective students acquire strong backgrounds in chemistry to complement my strengths as a biologist. During their first graduate year I made sure that they took rigorous courses in physical and organic chemistry. They might later use only a small fraction of this expertise, but they would never feel unqualified for experimentation at the molecular level.

4. Never let your students see themselves
as research assistants

It makes sense to have your students pursuing thesis objectives that genuinely interest you. At the same time you should take care that they never see themselves as working primarily for your professional advancement. Students function best when they can be assured of enjoying most of the credit for their efforts. After they came into my lab, generally only a month or two would pass before I backed away from their daily progress. I then let them work at their own pace and come into my office when they had results, either positive or negative, that I should be aware of. You know that they have become truly independent when they give thoughtful seminars before their lab peers. Novice speakers can profit from taking their licks when their conclusions go beyond what is justified by their data. Nothing banishes illogical conclusions from one's brain like the need to present them to others. Later I made it a point that my name never be included with theirs on research papers emerging from their experiments.

5. Hire spunky lab helpers

As an untenured scientist, most of your nonsleeping hours are spent in lab-related activities. Those working with me were effectively my surrogate family, with whom I would eat many meals and go to the beach or go skiing. So when hiring assistants to help with more routine lab management, I wanted to surround myself with faces that laughed at the right times and whose inherent positive outlook would be a calming influence when our experiments went nowhere. The best to have around were unmarried people of my own age; not yet saddled with family responsibilities, they were therefore not obliged to keep strictly regular hours. They could be called on for help in the evening hours or on weekends when we wanted our answers fast. In return, I treated them more as friends than as employees and didn't expect them to hang around when there was nothing particular to do.

6. Academic institutions do not easily change themselves

Most academic battles involve space or faculty appointments and promotions. All too often, academic life is a zero-sum game, with an equivalent loser for every winner. Sadly, most academic department heads and deans do not display long-term consistency, often maintaining their own academic power by giving to a professor what he or she was denied the year before. Before I went to Harvard, Leo Szilard told me that it moved only lethargically, an assessment based no doubt on his never having been asked to join its Physics Department. But he was also familiar with academia's general love of orthodoxy and warned that I should be realistic about how much change I could expect to see in a place as fossilized as Harvard's Biology Department. His pessimism would have been dead on had it not been for McGeorge Bundy's determination to see through a radical upgrade of biology at Harvard. University leaders with such strong convictions are rare.

8. MANNERS DEPLOYED FOR ACADEMIC ZING

U
PON the return of the Dotys from England, I needed a new place to live and luckily stumbled upon a vacant one-bedroom flat on the thousand-foot-long Appian Way, less than a five-minute walk from Harvard Square. Appian Way runs between Garden and Brattle Streets and is bordered on its northern side by Radcliffe Yard, where once virtually all of Radcliffe's classes were taught by Harvard professors. But with the disappearance of separate classes for women, the former classroom space in the Yard's Longfellow Hall was now used by the School of Education. Soon after my moving onto Appian Way, the Education School was to expand across it, in the process tearing down all its modest wooden homes except for number 10—the mid-nineteenth-century house, long owned by the Noon family, in which I occupied second-floor quarters. I regularly wrote out my bimonthly checks to Theodore W Noon, who had been at Harvard at the turn of the century and an instructor at Lawrenceville before the first Great War. Long retired from teaching, he was nearing eighty, and would eventually live to almost a hundred.

I was pleased to be told that among former 10 Appian Way tenants were the writers Owen Wister and Sean O'Faolain. The building's ancient central heating system was less charming. In winter I routinely needed an electric blanket to sleep. My flat's Spartan features were made for inexpensive furniture I bought from the Door Store on Massachusetts Avenue on the way to Central Square. Soon to complement its simplicity was a big-planked New Hampshire harvest table that I found in an antiques store near Falmouth on Cape Cod. I hoped its inherent elegance would inspire some Radcliffe girls to test their cooking talents in my tiny kitchen.

By early fall I had lost all hope that the astute geneticist Guido Pon-tecorvo would move from Glasgow to fill the senior geneticist's slot turned down by Seymour Benzer. Six months before, the ad hoc committee called to look over Benzer had also judged Ponte's accomplishments worthy of a major offer, a conclusion simultaneously reached by the electors of the soon-to-open chair of genetics at Cambridge. But Ponte had strong attachments to Glasgow, where his colleagues had solidly stood by him during the difficulties that followed his physicist brother Bruno's sudden flight to Moscow just before he was to be charged with treason for passing atomic bomb secrets to Soviet agents. Ponte, in turn, stood by his friends by refusing to go to either Cambridge.

That fall, knowing that I would be teaching undergraduates in the spring, I gave a graduate-level course on the biochemistry of cancer. During my previous winter weeks at the University of Illinois, I learned that uncontrolled cell growth should be the province of the biologist as well as the medic. There the biochemist Van Potter, from the University of Wisconsin, gave an evening colloquium on cancer, making me aware that at any given time most adult animal cells are not undergoing cell division. To duplicate their chromosomes and divide, these cells must receive molecular signals that initiate chains of events culminating in the production of enzymes involved in DNA synthesis. In contrast, cancer cells very likely do not require external signals to enter into cycles of growth and replication. Future searches for such intrinsic mitosis-inducing signals would quite likely involve the already long-known tumor viruses. Upon infecting so-called non-permissive normal cells, they do not initiate rounds of viral multiplication but rather transform the healthy cells into their cancerous equivalents. The Shope papilloma virus, already known for more than two decades to induce warts on rabbit skin, particularly intrigued me. Only a few genes were likely to be found along its tiny DNA molecules, made up of a mere five thousand or so base pairs.

Over the past summer at the Marine Biological Laboratory in Woods Hole, I had met the biochemist Seymour Cohen, then very upbeat about his lab's recent discovery that T2 phage DNA contains genes that code for enzymes involved in DNA synthesis. Initially I did not attach the proper importance to Cohen's finding, but I abruptly changed my mind several months later when preparing a lecture on Shope papilloma tumor virus. Then I found myself asking whether its chromosomes, like those of T2, also code for one or more proteins that trigger DNA synthesis. Since at any given moment the vast majority of adult cells do not contain the large complement of enzymes necessary to make DNA, conceivably all DNA animal viruses had genes whose function was to activate synthesis of these enzymes. Even more important, these genes, if somehow integrated into cellular chromosomes, might make the respective cells cancerous. I was in a virtually manic state as I presented these thoughts to my class. At last I understood the essence of a tumor virus. Over the following days, however, I realized that my excitement did not infect those about me. Only those who come up with the seductively simple ideas initially get hysterical about them. Everyone else demands experimental proof before joining the conga line.

I was still high on my theory by the time of a Sunday cocktail party given early in 1959 by David Samuels, the British-Israeli chemist who had recently arrived at Harvard as a senior postdoc under the bio-organic chemist Frank Westheimer. David was in line to be a British lord, like his father and his grandfather, the first Viscount Samuels, an influential early backer of a Jewish state in the holy land. Now he was still saddened over the death of his cousin Rosalind Franklin from ovarian cancer the past April. They had seen each other often during their school years. But after he chose Oxford and she Cambridge for their education as chemists, their paths less often crossed. It was only now that I realized that Rosalind had come from no modest background. Had she wished, she easily could have moved into the world of moneyed society that David now so obviously enjoyed when not applying himself as a serious chemist.

The most striking of David's guests that afternoon was the Radcliffe senior Diana de Vegh. Quickly making a move to her side, I learned that her investment banker father, Imre de Vegh, was a Hungarian, while her mother was a Social Register Jay. As such, she had sampled both Brearley and Miss Porter's School before being admitted to Rad-cliffe, where she had effectively managed to avoid any science. Now she lived in one of the off-campus houses favored by her fellow private school friends. Her comings and goings were much less conspicuous than would have been those of an inhabitant of one of the large red brick dorms surrounding the Radcliffe Quad up Garden Street. David, in observing Diana give me her telephone number as she went off to another party, took immediate pleasure in telling me that she had earlier attracted the attention of Senator John Kennedy. His official car recently had been sent from Boston to fetch her upon one of his recent returns to check in on his Massachusetts constituents.

Soon I was to phone Diana to ask her to lunch after one of my Biology 2 lectures. This new course, a one-term offering, was intended for students already possessing some background in biology. They would have benefited most from a coherent series of lectures given by one person, in the manner of the long-successful Chemistry 2 taught by Leonard Nash. But my department had opted for Biology 2 to have four instructors, thereby ensuring a virtual potpourri of facts and ideas for its students to master. But with me as one of its four instructors, DNA was bound to be much talked about.

The theme running through all my talks was the need to understand biological phenomena as expressions of the information carried within DNA molecules. Many, and I hoped most, students must have been desperate after nine lectures presented by the physiologist Edward Castle. The tall, thin Castle was bright but sad, habitually seen hurrying home by bike early each afternoon to a wife long stricken with multiple sclerosis. His lectures were a time warp back into the thirties. After listening to his opening talk, I could not have preserved my sanity listening to another. Three weeks later, before the same one hundred students in the Geological Museum auditorium, my first words were a promise that they would hear nothing more about the rabbit. The loud laughs that roared back assured me that I had broken the ice. After my last lecture, which was to be about cancer, I took Diana de Vegh to Henri IV, the French restaurant on Winthrop Street just off Harvard Square, run by the formidable Genevieve McMillan. Genevieve had masterminded the transformation of a modest wooden house into a popular space to have stylish French food with conversationally inclined companions. Looking into Diana's big eyes, I was in high spirits, for my lectures had gone well, with my impromptu attempts at humor appreciated.

Course notes for Biology 2, Lecture 1: “What Is Life”

That term Francis Crick was at Harvard as a visiting professor of chemistry. Even now, six years after the double helix had been found, Cambridge University had yet to provide him and his new South African-born collaborator, the prodigiously clever experimentalist Sydney Brenner, decent research space. Their experiments were being done in a wartime hut erected next to the Austin wing of Cavendish Lab, where the DNA base pairs had come together. The Harvard Chemistry Department, always wanting the best, had just offered Francis a professorship, but without much expectation of his acceptance. Here they were right, as Francis soon got news that the Medical Research Council would provide funds for the construction of a new laboratory building expressly for molecular biology. In fine intellectual fettle because his long-ignored adaptor hypothesis was now a widely accepted fact, Francis conversed endlessly on the details of how specific amino acids first become attached to their respective tRNA molecules. When he and I were awarded the Warren Triennial Prize at Massachusetts General Hospital, my talk surely was much less convincing than his, as I took the opportunity to propose my as yet unproven theory that the essence of DNA tumor viruses was their possession of genes that initiated DNA synthesis.

Ribosomal particles were proving much more structurally complicated than we anticipated, and Alfred Tissières persuaded the Welsh protein chemist Ieuan Harris to come over temporarily from Cambridge to help us. We initially had thought the particles would have the molecular simplicity of small plant viruses. But from his first amino end group analysis, Ieuan saw that ribosomes contained many more proteins than he could effectively cope with using current separation methodologies. So he took solace for the remainder of the spring in sampling American beers still new to him.

My lab group's size was steadily expanding despite the unwanted fleeing of my first graduate student, Bob Risebrough, to sea on the Woods Hole oceanographic sailing boat
Atlantis.
Much more content at their first contacts with molecular biology were two new graduate students, David Schlessinger and Charles Kurland. After working with Alfred to more firmly establish the two-subunit composition of ribosomes, David briefly went to Caltech to see if Matt Meselson's CsCi banding technique would reveal how long these subunits stayed together during multiple rounds of protein synthesis. That he came back empty-handed reflected his finding that even the ribosomal sub-units are unstable in high levels of CsCi. But the visit was far from a total loss: at Caltech David met the girl that he would later marry. He also discovered David Zipser, a very disenchanted first-year graduate student eager for a fresh chance at happiness at Harvard.

Chuck Kurland's first results on ribosomal structure were not at all what I expected. He found single RNA chains in each ribosomal sub-unit, with those present in the larger subunit twice the length of those in the smaller subunits. Before his observations we had anticipated a variety of RNA chain lengths, reflecting their respective functions to convey information for different-sized polypeptide chains. A year later, Matt Meselson and Rick Davern discovered that once made, these ribosomal RNA chains were very stable under optimal conditions for protein synthesis. Yet at the time of our discoveries, Francois Jacob, Jacques Monod, and Arthur Pardee at the Institut Pasteur in Paris had evidence that the RNA templates for so-called induced enzymes had fleeting lives of only a few minutes. This apparent contradiction came to a head at a Copenhagen meeting in the late summer of 1959, at which Jacques Monod questioned the view that RNA had to be the template for all protein synthesis. Could, in fact, DNA molecules be the templates for the synthesis of the so-called induced enzymes? I rejected this hypothesis during my terse report of our ribo-some discoveries. Unfortunately, my talk's only lively moment came at its start, and not from its content. Everyone in the front row brought out a copy of the
New York Times
to read—a brainchild of Sydney Brenner, who had long noticed with envy my ability to follow talks while simultaneously keeping abreast of daily events.

Earlier in the summer the Japanese biochemist Masayasu Nomura, then a postdoc in Sol Spiegelman's Urbana lab, came briefly to my lab on his way to the 1959 phage course at Cold Spring Harbor. He had spent the previous summer with me and Alfred characterizing abnormal ribosomes made under conditions of chloromycetin inhibition of protein synthesis. Now a year later and still unable to judge their biological significance, I suggested to Masayasu that he use his forthcoming phage course experience to look at the molecular form of the unstable RNA made during T2 infection. I had been long attracted to T2 RNA because its base composition was almost identical to that of the T2 phage DNA and possibly represented RNA copies of the information present in T2 DNA genes. Though potentially very important, the phenomenon eluded further characterization. What T2 RNA was should at last be revealed by the new techniques of sucrose gradient centrifugation, which required only small amounts of RNA and would potentially provide information about its function through measurements of the sedimentation rate of its radioactively labeled molecules.