Avoid Boring People Part 3

Still to be ascertained was how the information conveyed by the sequence of DNA's four bases (adenine, guanine, thymine, and cyto-sine) determines the order of the amino acids in the polypeptide products of individual genes. Since there were known to be twenty amino acids and only four DNA bases, groups of several bases must be used to specify, or code for, a single amino acid. I initially thought the language of DNA then would be best approached not through further work on the DNA structure but by work on the 3-D structure of its close chemical relative ribonucleic acid (RNA). My decision to move on from DNA to RNA reflected the observation, already several years old, that polypeptide (protein) chains are not a.s.sembled on DNA-containing chromosomes. Instead they are made in the cytoplasm on small RNA-containing particles called ribosomes. Even before we found the double helix, I postulated that the genetic information of DNA must be pa.s.sed on to RNA chains of complementary sequences, which in turn function as the direct templates for polypeptide synthesis. Naively I then believed that amino acids bonded to specific cavities linearly located on the surfaces of the ribosome RNA components.

Three subsequent years of X-ray studies-the first two at Caltech and the last back with the "Unit" in Cambridge, England, in which I was joined by the Pauling- and Harvard Medical School-trained Alex Rich-frustratingly failed to generate a plausible 3-D structure for RNA. Though RNA from many different sources produced the same general X-ray diffraction pattern, the pattern's diffuse nature gave no solid clues as to whether the underlying RNA structure contained one or two chains. By early 1956 I decided to change my focus from X-ray studies on RNA to biochemical investigations on ribosomes when I began teaching in the fall at Harvard. Also then seeking a more tractable challenge was the Swiss-born biochemist Alfred Tissieres, then studying oxidative metabolism at the Molteno Inst.i.tute in Cambridge. He had already briefly dabbled with ribosomes from bacteria and liked the idea of our seeking out how they work across the Atlantic in the other Cambridge.

Alfred came from an old Valais family that long owned a bank in Sion. When he was less than a year old his banker father tragically died during the great influenza epidemic of 1918. Much later a minor inheritance let Alfred possess the sleek Bentley that he parked across the Cam on land adjacent to the school for the famed King's College boys' choir. An even greater source of pride than his car was Albert's election to the British Alpine Club in 1950. His formidable ascents of the south face of the Taschhorn and the north ridge of the Dent Blanche led to an invitation to join the Swiss 1951 Everest reconnaissance expedition. Regretfully he had to decline, giving priority to his research efforts in the Molteno Inst.i.tute that led, in 1952, to a research fellowship at King's. Climbing, however, always remained essential to his psyche. In the summer of 1954 he joined in the Alpine Club's reconnaissance of Pakistan's Rakaposhi, at almost eight thousand meters high one of the Karakoram's most daunting peaks.

Alfred Tissieres braves an airy traverse of the Gilgit River in northern Pakistan in 1954.

After I left for Harvard, my successor as the Unit's geneticist was to be the South African-born Sydney Brenner. We first met when he was working for a Ph.D. at Oxford following medical training in Johannesburg. In the spring of 1953, Sydney was among those to have come to Cambridge to have a peek at our big molecular model of the double helix. He entered our lives more importantly, however, during the summer of 1954, when Francis and I were at Woods Hole on Cape Cod, talking genetic codes with the Russian-born, big bang theoretical physicist George Gamow. Then learning bacterial genetics at Cold Spring Harbor, Sydney came to Woods Hole for several days, greatly impressing Gamow and Francis by his quickness to catch on to their ideas and to propose experiments to test them.

Gamow, then a professor at George Washington University, was first drawn to the double helix through his reading in the summer of 1953 of our second Nature Nature paper on the subject ("Genetical Implications of the Structure of DNA"). By early 1954, his seemingly wacky initial ideas had crystallized into a precise mechanics for the genetic code by which overlapping groups of three nucleotides coded for successive amino acids along polypeptide chains. On an early May 1954 visit to Berkeley, where George was on sabbatical, I proposed that we form a twenty-person code-seeking club, one member for every amino acid. George instantly reacted positively, much antic.i.p.ating designing a tie and stationery for our RNA Tie Club. paper on the subject ("Genetical Implications of the Structure of DNA"). By early 1954, his seemingly wacky initial ideas had crystallized into a precise mechanics for the genetic code by which overlapping groups of three nucleotides coded for successive amino acids along polypeptide chains. On an early May 1954 visit to Berkeley, where George was on sabbatical, I proposed that we form a twenty-person code-seeking club, one member for every amino acid. George instantly reacted positively, much antic.i.p.ating designing a tie and stationery for our RNA Tie Club.

Though there was never a convention of all its members, "notes" that circulated within the RNA Tie Club greatly advanced thought about genetic codes. The most famous of these notes, by Francis, in time would totally change the way we thought about protein synthesis. In January 1955 he wrote to the RNA Tie Club correctly suggesting that amino acids, prior to being incorporated in polypeptide chains, would attach to small RNA adaptors that in turn bind to template RNA molecules. For each amino acid, Francis postulated, there must exist a specific adaptor RNA (now called transfer RNA). In the absence then of any experimental evidence for small RNA, much less their chemical binding to amino acids, even Francis could not long remain buoyant about his adaptors. Six months were to pa.s.s before he was to regain a manic mood, but this time it was over a 3-D model for collagen that he and Alex Rich built over the summer of 1955.

After Alex returned in December to his job at the National Inst.i.tutes of Health outside Washington, D.C., Francis and I focused for the winter of 1956 on the structures of small spherical RNA viruses, outlining how their cubic symmetry resulted from the regular aggregation of smaller asymmetrical protein building blocks. How their single long RNA chains were organized with their polyhelical protein sh.e.l.ls remained to be seen. Our last time as a team of two was at a Johns Hopkins University-organized symposium in mid-June 1956, ent.i.tled "The Chemical Basis of Heredity." Upon arriving at the Hotel Baltimore, Francis jubilantly pointed out that we had been a.s.signed adjacent rooms in the top-floor presidential suite.

After that occasion staying at the top was to be a challenge we would have to face separately.

Remembered Lessons 1. Choose an objective apparently ahead of its time Mopping up the details after a major discovery has been made by others will not likely mark you out as an important scientist. Better to leapfrog ahead of your peers by pursuing an important objective that most others feel is not for the current moment. The 3-D structure of DNA in 1951 was such an objective, regarded by virtually all chemists as well as biologists as unripe. One well-known scientist then toiling in DNA chemistry predicted that a hundred years would pa.s.s before we knew what the gene looked like at the chemical level. Before setting out, you need to figure out a new path by which to climb-or, even better, a new intellectual catapult that can potentially hurl you over creva.s.ses seemingly too broad to be leapt over by experimentation. The model-building approach to the DNA structure in 1951 had the potential to let us get where we needed to go at a time when the more orthodox approach, limited to a.n.a.lyzing X-ray diagrams, was far from straightforward. Given Pauling's recent success using molecular modeling to find the a-helix, using this approach on DNA was far from outlandish; actually, it was a no-brainer.

2. Work on problems only when you feel tangible success may come in several years Many big goals are truly ahead of their time. I, for one, would like to know now where exactly my home telephone number is stored in my brain. But none of my colleagues who think about the brain yet know even how to approach this problem. We might do very well by asking how the cells in the much, much smaller fly brain are wired so as to recognize the odor of a specific alcohol-that would be getting us somewhere.

I feel comfortable taking on a problem only when I believe meaningful results can come over a three-to-five-year interval. Risking your career on problems when you have only a tiny chance to see a finish line is not advisable. But if you have reason to believe you have a 30 percent chance of solving over the next two or three years a problem that most others feel is not for this decade, that's a shot worth taking.

3. Never be the brightest person in a room Getting out of intellectual ruts more often than not requires unexpected intellectual jousts. Nothing can replace the company of others who have the background to catch errors in your reasoning or provide facts that may either prove or disprove your argument of the moment. And the sharper those around you, the sharper you will become. It's contrary to human nature, and especially to human male nature, but being the top dog in the pack can work against greater accomplishments. Much better to be the least accomplished chemist in a super chemistry department than the superstar in a less l.u.s.trous department. By the early 1950s, Linus Pauling's scientific interactions with fellow scientists were effectively monologues instead of dialogues. He then wanted adoration, not criticism.

4. Stay in close contact with your intellectual compet.i.tors In pursuing an important objective, you must expect serious compet.i.tion. Those who want problems to themselves are destined for the backwaters of science. Though knowing you are in a race is nerve-racking, the presence of worthy compet.i.tors is an a.s.surance that the prize ahead is worth winning. You should feel more than apprehensive, however, if the field is too large. This usually means you are in a race for something too obvious, not enough ahead of its time to deter the more conservative and less imaginative majority. The presence of more than three or four compet.i.tors should tell you that your chance of winning is not only low but virtually incalculable since you are unlikely to have a detailed knowledge of the strengths and weaknesses of most of your compet.i.tion. The smaller the field, the better you can size it up, and the better the chance you will run an intelligent race.

Avoiding your compet.i.tion because you are afraid that you will reveal too much is a dangerous course. Each of you may profit from the other's help, and an effective dead heat that allows you to publish simultaneously is obviously preferable to losing. And if it happens that someone else does win outright, better it be someone with whom you are on good terms than some unknown compet.i.tor whom you will find it hard not to at least initially detest.

5. Work with a teammate who is your intellectual equal Two scientists acting together usually accomplish more than two loners each going their own way. The best scientific pairings are marriages of convenience in that they bring together the complementary talents of those involved. Given, for example, Francis's penchant for high-level crystallographic theory, there was no need for me also to master it. All I needed were its implications for interpreting DNA X-ray photographs. The possibility, of course, existed that Francis might err in some fashion I couldn't spot, but keeping good relations with others in the field outside our partnership meant that he would always have his ideas checked by others with even greater crystallographic talents. For my part, I brought to our two-man team a deep understanding of biology and a compulsive enthusiasm for solving what proved to be a fundamental problem of life.

An intelligent teammate can shorten your flirtation with a bad idea. For all too long I kept trying to build DNA models with the sugar phosphate backbone in the center, convinced that if I put the backbone on the outside, there would be no stereochemical restriction on how it could fold up into a regular helix. Francis's scorn for this a.s.sertion made me reverse course much sooner than I would have otherwise. Soon I too realized that my past argument had been lousy and, in fact, the stereochemistry of the sugar-phosphate groups would of course move them to outer positions of helices that use approximately ten nucleotides to make a complete turn.

In general, a scientific team of more than two is a crowded affair. Once you have three people working on a common objective, either one member effectively becomes the leader or the third eventually feels a less-than-equal partner and resents not being around when key decisions are made. Three-person operations also make it hard to a.s.sign credit. People naturally believe in the equal partnerships of successful duos-Rodgers and Hammerstein, Lewis and Clark. Most don't believe in the equal contributions of three-person crews.

6. Always have someone to save you In trying to be ahead of your time, you are bound to annoy some people inclined to see you as too big for your britches. They will take delight if you stumble, believing your reversals of fortune are deserved. They may reveal themselves only in the moment of your discomfiture: often you find them controlling your immediate life by, say, determining whether you will get your fellowship or grant renewed. So it always pays to know someone of consequence-other than your parents-who is on your side. My hopes to go for broke with DNA by going to Cambridge would have gone nowhere if my phage-day patrons, Salvador Luria and Max Delbruck, had not come to my rescue when my request to move my fellowship from Copenhagen to Cambridge was turned down. I was then judged, not without cause, to be unprepared for X-ray crystallography and urged to move instead to Stockholm to learn cell biology. Immediately John Kendrew offered me a rent-free room in his home, while Luria, through a personal connection, got my fellowship extended for eight months. Soon after, Delbruck arranged a National Foundation for Poliomyelitis fellowship for the succeeding year. In finding the funds that kept me in Cambridge, Luria and Delbruck were hoping that my new career as a biological structural chemist would succeed and do them proud. But they fretted about my being too far from their fold, knowing that I would likely leave empty-handed from my long Cambridge stay. The second year of my fellowship was, in fact, to be spent at Caltech, giving me at least a measure of security in the event the DNA structure was solved by others. In leaving one field for another, it never makes sense to burn your past intellectual bridges at least until your new career has taken off.

7. MANNERS PRACTICED AS AN UNTENURED PROFESSOR.

THE HARVARD to which I moved in the fall of 1956 thought of itself as the best university in the United States. Most certainly it was the oldest, and with its endowment the largest of any university's, it saw no reason not to have the most distinguished faculty of any inst.i.tution on the planet. Before any tenure appointment, a group of eminent experts in the field were a.s.sembled to advise the president as to how the proposed candidate ranked among peers worldwide. The use of such ad hoc committees dated from the administration of James Conant, a distinguished organic chemist and only the second scientist ever to lead Harvard. Taking over from Lawrence Lowell in 1933, he presided for twenty years, resigning in 1953 to serve as U.S. high commissioner and later amba.s.sador to Germany. Deeply involved in the military-related science that helped the United States win World War II, he seized upon the improvements in the nation's scientific capability to raise the bar correspondingly at Harvard's mathematics, physics, and chemistry departments.

The Harvard biology faculty contained several world-cla.s.s scientists, in particular the vision biochemist George Wald and the evolution authority Ernst Mayr. But too many of its faculty had pedestrian outlooks incommensurate with the quality of most Harvard students. All too typical was the Biology Department's uninspired introductory course. It abounded in dull facts for its largely premedicai enrollees to memorize. One year its abject dreariness provoked the studentwritten "Confidential Guide" to suggest that one of its instructors might do well to shoot himself.

Unlike Caltech, where genetics was the dominant biological discipline, Harvard's department, then chaired by the pedantic amber insect specialist Frank Carpenter, did not treat one field of biology as any more important than another. Together with his forlorn a.s.sistant, the former Rhodes scholar Orin Sandusky, Carpenter lumberingly oversaw the department's day-to-day activities in the ma.s.sive five-story Biological Laboratories. It was built in the early 1930s in brick textile factory style, much of the money for its construction coming from the General Education Board of the Rockefeller Foundation, whose members wanted the benefaction to promote research as opposed to teaching. The nonexistence of a Biolabs lecture hall big enough for large biology cla.s.ses was thus not a mistake but a matter of principle.

By the time the construction of the Biolabs started in 1932, the Depression had arrived and funds to outfit the north wing never materialized. Twenty-five years later, this wing's long empty factorylike floors suggested themselves to me as more than sufficient s.p.a.ce for DNA-based biology to thrive at Harvard if the university was so inclined. Equally important to this objective, many senior faculty members were on the verge of retiring. Their large square corner offices, connecting to secretarial areas, themselves big enough for professors in less prestigious inst.i.tutions, would soon be free. No lunchroom existed within the Biolabs either, and at noon the notables set off for the Georgian-style Faculty Club on Quincy Street. There they invariably lunched by themselves around the same rectangular table just inside the main dining room. Administrative minutiae, not ideas, dominated most conversations, with food chosen from a menu featuring horse steak, a proud holdover from wartime's austerity. Off the main dining room and usually entered by its own outside entrance was a separate room for women guests. Then there were effectively no women on Harvard's Faculty of Arts and Sciences.

With its corridor walls seemingly unpainted for at least a decade, the Biolabs' only sparkle came from the two enormous bronze rhinoceros that flanked the main entranceway. They had been sculpted by a talented friend of President Lowell's, who also designed the friezes of wild animals that ran above the courtyard. The vision of biology these figures conveyed meshed well with the mission of Harvard's nearby Department of Geographical Exploration, its building still topped by the radio antenna once used to keep in touch with members out beyond the fringes of Western civilization. But that department no longer existed. Rumor had it that President Lowell had been horrified to learn that several of its members were h.o.m.os.e.xuals. So its handsome one-story brick edifice was now the center of Harvard's Far Eastern studies, where the savvy John King Fairbank and Edwin O. Reischauer held sway.

Even closer to the Biolabs along Divinity Avenue was the Semitic Museum, donated by the banker Jacob Schiff at the end of World War I to encourage the study of ancient Jewish culture. But now most of its facilities were occupied by the Bob Bowie- and Henry Kissinger-led Harvard Center for International Affairs (HCIA), whose acronym encoded the ident.i.ty of its secret government funder, which had an interest in training Harvard's students as the possible future leaders of the free world.

On the far side of the elm-lined gra.s.sy courtyard in front of the Biolabs stood what once had been the princ.i.p.al dormitory of the Harvard Divinity School. Ralph Waldo Emerson was said to have lived there early in the nineteenth century. But such historical facts mattered little to James Conant, under whose presidency the Divinity School's long minor role in Protestant theological training had withered almost to extinction. Just before my arrival, religion at Harvard was given a new lease on life through the appointment of Nathan Marsh Pusey as its next president. Born in Iowa in 1907, Pusey had studied cla.s.sics as a Harvard undergraduate and had obtained his Ph.D. there at the age of thirty. After teaching at Lawrence, Scripps, and Wesleyan colleges, he returned to Wisconsin as president of Lawrence College in 1944. There he was to achieve postwar renown by speaking out against his state's junior senator, Joseph McCarthy. In choosing him as James Conant's successor, the five members of the Harvard Corporation saw themselves reaffirming the importance of a strong moral overtone in higher education. They were not unduly concerned that Pusey did not have the intellectual distinction to be a member of its faculty. Later they were to silently realize that his writings never sparkled and that his addresses to both students and faculty were occasions of neither enlightenment nor inspiration. And when they inevitably built a library in his memory, it was a below-ground structure intended to store archives.

To Pusey's credit, he accepted the Corporation's advice to appoint a first-cla.s.s dean of the Faculty of Arts and Sciences. Whether he knew that in McGeorge Bundy he was choosing someone who would outcla.s.s him on virtually any occasion they were together, we will never know. A Boston blueblood by birth, Bundy came to Harvard via Groton and a brilliant undergraduate career at Yale. At Harvard he was initially one of the elite junior members of the Society of Fellows, later joining the Government Department and securing tenure by the time he became Harvard's most important dean. All appointments to the Faculty of Arts and Sciences would be administered by him, and it was he who would choose the ad hoc committees whose deliberations he and President Pusey invariably attended.

It is highly unlikely that Bundy had any role in Pusey's ill-fated decision, made in his second year as president, to deny the request of a Jewish student to be married in Harvard's imposing Memorial Church, built in the 1920s in memory of the American fallen of the First World War. In so doing, Pusey aroused the wrath of his faculty. A prominent delegation came to his office to tell him that Harvard's church should be open to those of all faiths, not restricted to Christians. It was a grievance rooted in history. Many years before, Jews had been effectively blackballed from faculty positions. Those faculty who had come to the president's office were determined that such bigotry as had stained Harvard's past would not corrupt its present. Sensing a fight that would effectively destroy the moral authority for which he was appointed, Pusey reversed his edict and the incident soon faded from view.

For Harvard's president, however, it was deeply wounding to be told that his initial response, which he regarded a reaffirmation of his inst.i.tution's long Protestant heritage, was an expression of anti-Semitism.

From that moment on, Pusey never again saw his faculty as allies and became socially isolated from them during his remaining eighteen years as president. For friendship, he and his wife, Anne, would turn to the governing boards. They became summer residents of Seal Harbor on Mt. Desert Island, Maine, close to the home of David Rockefeller, soon to become chairman of Harvard's Board of Overseers. Both leaders felt similarly about the importance of religion, with Rockefeller making a major gift to strengthen the faculty of the Divinity School.

My decision to leave Caltech for Harvard was facilitated by a growing friendship with the chemist Paul Doty, whose laboratory in Gibbs Lab was just across Divinity Avenue from the Biolabs. Paul, trained initially as a physical chemist and then a polymer chemist, began physical-chemical studies of DNA only after moving to Harvard in 1948. Eight years older than I, he had just become a full professor when I arrived at Harvard. Fortunately for me, he was one of a handful of key faculty to whom McGeorge Bundy regularly turned for advice. So while many Harvard biologists remained uncertain as to whether I belonged in their department or in chemistry, Bundy, through Paul, knew I was a true biologist and hoped I'd help make the biology department into one comparable in stature to the ones in chemistry and physics.

Rea.s.suring me that my academic life would not be totally at the whim of old-fashioned biologists was the recent formation of the Committee for Higher Degrees in Biochemistry, whose members were to be drawn from suitable individuals in the Biology and Chemistry departments. As a member from Biology, I would help choose the first cla.s.s of graduate students and advise on appropriate courses for their first year. My first research student, Bob Risebrough, had been admitted as a Biology Department graduate student. As an undergraduate at Cornell, his main focus had been ornithology. Now he was excited by DNA, and his best introduction to it, I decided, might be to do a thesis on the properties of phage 9174, then reported to be much smaller than any other known phage. Its DNA molecules might be correspondingly smaller, thus perfectly suited to Paul Doty's physical chemistry instrumentation. Later I put my first biochemistry graduate student, Julian Fleischman, to work on the task of establishing the sizes of the DNA molecules in the much bigger T2 phage. Conceivably each T2 particle contained several DNA molecules held together end to end by protein linkers. Studying them might provide a good model for how DNA is arranged in the chromosomes of higher cells.

When Paul Doty ominously told me that promotions to tenure were often decided based on teaching evaluations, I realized I couldn't give the old-fashioned biologists a reason to suggest I might be better suited to a pure research inst.i.tution or medical school. My attention focused sharply in my first months on my teaching a.s.signments. Invariably worried that I would not have enough material memorized to occupy the next instructional hour, I meticulously outlined all my coming lectures. By doing so, I could offer my virus course students, largely advanced undergraduates, copies of the outlines, thereby relieving them of the need to take notes. Few students, however, availed themselves of this opportunity, continuing to be so soph.o.m.or-ically absorbed in note taking that their faces never revealed whether they were following my arguments. Fortunately, not too many stumbled in the hourlong midterm exam. And remembering the long-term benefits that had accrued to me at Indiana University from writing term papers on personally intriguing research topics, I asked them to write ten to fifteen pages on something in the course that particularly caught their fancy.

Initially I hoped to effect my social integration into the Harvard scene by living in one of the large undergraduate residence halls. Called houses, their creation realized President Lowell's wish to establish between Harvard Yard and the Charles River replicas of the Cambridge and Oxford colleges. As such, they would have young unmarried "tutors" living in specially designed suites. I asked my departmental chairman, Frank Carpenter, about the possibility, and he advised I try Leverett House, where the master was the embryolo-gist Leigh Hoadley. Though he had long given up even a pretense of being a scientist, I saw no reason to a.s.sume Leigh would prove equally useless as a house master. All too soon, however, I discovered that the "bunny hutch," as Leverett House was then known, was never a first choice for undergraduates and that its so-called high table was the ant.i.thesis of what I had known in Cambridge. We ate the same uninspired food as the undergraduates, and conversation followed the lead of Master Hoadley, incapable of either levity or deep thought.

The ersatz high table might have mattered less if I had been provided with adequate living quarters. But my so-called suite did not look out on the Charles, its only view being to the opaque bathroom window of the master's apartment. My psyche was not helped by Hoadley's later admission that he might have given me accommodations more appropriate for a dog. I saw no reason to immediately let him know when I moved to a one-room flat carved out of a large house on nearby Francis Avenue. My first lab a.s.sistant, Celia Gilbert, daughter of the radical journalist I. F. Stone, had told me that her father's friend Helen Land had a vacancy nearby. It was one of several such small flats that I later realized were rented mainly to individuals with leftist connections. As I moved in, the journalist-to-be Jonathan Mirsky was moving out of the same building. His apartment was later occupied by a government graduate student, Jim Thomson, whom I would later meet when he became a member of the National Security Council.

In coming to Harvard still unmarried, I was more than conscious of goings-on at the once quite separate women's college, Radcliffe. Its residence halls were less than a mile away, and after the war cla.s.ses at both colleges became entirely coeducational. Only the undergraduate Lamont Library remained out of bounds for women. How to go about meeting Radcliffe girls was not obvious, as their occasional mixers, then called jolly-ups, never seemed to bring forth the ones you would want to be seen with. Luckily, the geneticist Jack Schultz had a daughter, Jill, whom I had known earlier in Cold Spring Harbor, and who was now a Radcliffe senior living in a small wooden house off campus on Ma.s.sachusetts Avenue. Soon I was to meet several of her housemates and gradually acquired the confidence to show up unannounced for after-dinner coffee.

Eating by myself in the faculty club was never an event to be antic.i.p.ated and so I always greatly welcomed invitations to dine with the Dotys, now living less than a thousand feet from Paul's lab in a huge mansard-roofed house on Kirkland Place. Equally important in maintaining my morale were dinners at Wally and Celia Gilbert's equally proximate flat. We had met the year before at Cambridge University, where Wally had gone from Harvard as a young theoretical physicist. Knowing that they soon would be going back to Harvard upon completion of Wally's Cambridge Ph.D., I offered Celia, who had been an English major at Smith, a job at my lab starting in the fall. With Celia about, even routine lab manipulations became moments of conversational mischief. But after only four Biolab months, she was struck with mononucleosis. Her illness ended her tenure in my lab and, perhaps as a small consolation, the anxiety she suffered when called upon to dilute phage solutions by factors as big as a million.

Subtle conversational moments returned in March when Alfred Tissieres, with his Bentley, arrived from Cambridge. Soon finding himself a room in a house off Brattle Street, he took on the task of finding a lab technician to replace Celia. Happily, Kathy Coit, whose parents were now housing Alfred, expressed interest in joining us. Finding her not only intelligent but also an enthusiastic rock climber, Alfred persuaded her to become our factotum. Though this was her first exposure to science, Kathy's cheerful common sense soon made her indispensable to our day-to-day lab progress.

Covering Alfred's salary was a grant that I had obtained from the National Science Foundation to study the ribosomes of bacteria. Those funds also allowed us to buy a preparative Spinco ultracentrifuge needed to spin them away from other bacterial components. A more expensive a.n.a.lytic Spinco that could measure how fast ribosomes sedimented was needed, too, but my grant wouldn't stretch that far. Luckily, we had one at our disposal thanks to the protein chemist John Edsall on the floor above.

Most evenings I would be back in the lab, having already spent the daylight hours there. After hours, we were required to sign the night watchman's sign-in book. There was no good reason for its existence except catching an errant husband in a lie concerning his whereabouts of an evening. One night I entered and was pleased to find it had gone missing, with no untoward consequences for the building's proper function. More frustrating was the bolting of the departmental library when the dour librarian went home. Though faculty members had keys, graduate students didn't and could not search out journal references in the evenings or on weekends. My continued pestering for the department to pay students to guard the entrance finally led to that reform for the common good.

Harvesting tobacco mosaic virus in 1958. From left to right: Julian Fleischman, Kathy Coit, John Mendelson, and Chuck Kurland Nathan Pusey regularly opened Harvard's stately President's House to his faculty and their spouses for Sunday afternoon tea and cakes. Paul Doty urged me to sample such an occasion, and I semiawkwardly presented myself at the front door when my fall term lectures were nearing their end. Led by a maid into the main drawing room, where I introduced myself to the Puseys, I soon was pa.s.sed along to talk with the late-thirtyish Swedish theologian Krister Stendahl and his equally youthful wife, Brita. A prize catch in Pusey's efforts to resurrect the Divinity School, Stendahl had a strong, angular, slightly distorted face that struck me as that of a troubled minister in an Ingmar Bergman film. Liking his reasoned openness to the complexities of human life, I nevertheless could not even affect interest in the Evangelist Matthew, about whom he had just completed a scholarly tome. Later, when Anne Pusey moved to be near me, I felt much more at ease talking about my Chicago education and how fortunate I felt to be part of the Harvard scene. Simultaneously I tried to overhear what our president was saying to others. Later, as I walked out onto Quincy Street, I wondered whether any conversational gambit could possibly elicit from him an animated response.

Later during the monthly meetings of the Faculty of Arts and Sciences, I was no more successful at discerning the feelings that occupied what he considered to be his soul. We always turned to Bundy for hints of what was coming next. Pusey seemed to come to life only when presenting honorary M.A.'s to those newly tenured faculty whose actual degrees had been conferred elsewhere. Through this gesture of sanctification, Harvard saw itself as ensuring that all faculty felt equally valued.

My social life at Harvard still left much to be desired. I had flown to London just before Christmas, and then for the New Year had gone by train up to the home of d.i.c.k and Naomi Mitchison on the Mull of Kintyre in the Scottish Highlands. My first visit to their Carradale House had been five years before, when I was invited by their youngest son, Avrion, then doing his Ph.D. thesis in Oxford on the immunolog-ical response. Av's mother was a distinguished writer of leftist persuasion, so I could again count on being part of an intellectual house party that featured long walks over boggy moors, heated conversations much more about politics than science, and hearty but never inspiring food. Still, I knew it would be much more fun than going back to the small home in the Indiana sand dunes to which my parents had moved after my sister's graduation from the University of Chicago. I would later regret not having been a more dutiful son when my mother, only fifty-seven, died of a sudden heart attack not long after the holidays. She never had the pleasure of visiting Harvard to see me as a member of its faculty. When I went home for her funeral, I could see my father was unlikely ever to recover entirely from her unexpected death.

At the end of July, I was happy to be able to bring my father along to the Isle of Skye, where I was to be the best man at Av Mitchison's wedding to Lorna Martin. It was my first chance to meet Av's intellectually powerful research supervisor, Peter Medawar. He came up from London with his strong-willed wife, Jean, and fetching bright daughter, Caroline, then intending to escape from much unwanted parental dating advice by going up to Cambridge. In the middle of the reception, I had no difficulty in spiriting Caroline away for a long car ride through the wild beauty of Skye, remaining absent long enough for Peter and Jean to grow worried that Caroline and I might have found each other perfect. But she had other plans for the next few weeks. And after putting my father on a plane back to Chicago, I antic.i.p.ated intersecting in Tuscany with a Radcliffe girl I knew from the off-campus house on Ma.s.sachusetts Avenue, who was traveling in Europe. Several letters from the prior locales on her itinerary gave me to believe that she would greet me warmly when our paths finally crossed in a.s.sisi. But as we looked up at the Giotto frescos on the walls of its fifteenth-century basilica, I sensed that her affections were already subscribed; I later learned she was smitten with a young cla.s.sics instructor.

Even before I went off to Europe, momentum was building for the appointment of a super geneticist to the biology faculty. Bagging such a star had been on Harvard's agenda since the late 1940s, when an offer failed to lure Tracy Sonneborn away from Indiana. Now the introductory course was being taught by Paul Levine, whose recent promotion to a tenured position had been a dicey matter. In so proposing him, the senior biology faculty had to emphasize his highly praised teaching, since his middling research on Drosophila Drosophila was far from noteworthy. Given Bundy's known determination to prevent his out-of-date biology faculty from perpetuating their inherent mediocrity, the promotion had hints of a compromise between him and Pusey The letter from University Hall to the Biology Department stated that Levine's appointment was conditional upon the department's next tenured slot being reserved for a geneticist whose research was world-cla.s.s. Initially I feared that they might somehow find a candidate who, though clever, did not yet feel it necessary to think in terms of the double helix. Fortunately, I could not have been more wrong. was far from noteworthy. Given Bundy's known determination to prevent his out-of-date biology faculty from perpetuating their inherent mediocrity, the promotion had hints of a compromise between him and Pusey The letter from University Hall to the Biology Department stated that Levine's appointment was conditional upon the department's next tenured slot being reserved for a geneticist whose research was world-cla.s.s. Initially I feared that they might somehow find a candidate who, though clever, did not yet feel it necessary to think in terms of the double helix. Fortunately, I could not have been more wrong.

The subsequent departmental committee made the Purdue University phage geneticist Seymour Benzer, already my close friend, number one on their list. Decisive was the maize geneticist Paul Mangelsdorf's highly positive reaction to Benzer's recent talk before the International Congress of Genetics in Toronto. Within days of Seymour's coming to Harvard to talk about his fine-structure genetic map of the r2 gene of phage T4, my senior biology colleagues voted unanimously for his appointment. Seymour, of course, had been earlier apprised of the department's intentions. Paul Doty and I both told him that it was virtually impossible for any properly const.i.tuted ad hoc committee not to back his addition to the Harvard faculty.

Alfred Tissieres was now Bentley-less. In July he was to marry in Colorado the equally strong-willed Virginia Wachob, a girl of Scottish descent from Denver, whom he first met at Caltech during a year away from King's. Supporting both a wife and a Bentley, which soon might need a major engine overhaul, would not be possible given that Alfred's Harvard salary was slightly lower than mine. The Bentley now belonged to a much more handsomely rewarded law school professor.

With the a.s.sembling of the ad hoc committee taking longer than expected, it was early February 1958 before Seymour had his formal offer and an invitation back to Harvard to meet with Bundy Then he wanted rea.s.surance that DNA-based biological thinking would have the continued strong support of the administration. To my distress, Seymour didn't immediately accept, implying worry at having greater teaching responsibilities than at Purdue. And so it was a great relief when Bundy happily called me early the next week with news that Seymour's letter of acceptance was on his desk.

Going off soon thereafter to the University of Illinois, as its George D. Miller Visiting Lecturer in Bacteriology, I could finally rest a.s.sured that the days of backward thinking in Harvard's Biology Department were numbered. My visit was arranged by Salva Luria, who by then had been a professor at Urbana for more than five years. My lectures on macromolecular replication and cell growth were a preview of ones I wanted to deliver later to Harvard undergraduates. Over the three weeks of my visit, I enjoyed much stimulation from the Urbana science scene. Especially enjoyable was talking with the diminutive, manic Sol Spiegelman, then also focusing much of his research on ribosomes.

Flying back to Boston on an intellectual high, I came back down to earth at Harvard with a thud. Seymour Benzer now claimed a heart condition that forced him to reverse his decision to come. Staying in Purdue, with its almost nonexistent teaching responsibilities, would be much less taxing, and he had to think of his health. The disappointment might have been unbearable if Av Mitchison had not happened to be in residence for the spring term, giving an advanced course on immunology. To my delight, he and his new wife, Lorna, together with Alfred Tissieres and I, were temporarily occupying the Dotys' big house on Kirkland Place while the Dotys spent Paul's long-overdue sabbatical in the other Cambridge. Parked next to my MG TF beneath the Dotys' main bedroom was Alfred's consolatory sleek new Alfa Romeo sedan.

Had it not been for Doty's occasional flights back to oversee his ever-growing lab group, my direct line to McGeorge Bundy would have been cut off when I most needed it. With virtually no warning, I learned that an ad hoc committee soon would a.s.semble to consider simultaneously the promotions from a.s.sistant professor to tenured a.s.sociate professorship of Edward O. Wilson and myself. That I was to be considered a year prematurely was not at all the original intent of the Biology Department. Their concern primarily was Wilson, whom they needed to promote to keep him from accepting the same terms from Stanford. After undergraduate education as a naturalist in his home state of Alabama, Ed had moved north to Harvard to pursue a Ph.D. Proving his brilliance during his initial studies on ants and their behavior, he became a junior fellow, then considered the best stepping-stone to an eventual permanent position on the faculty. Since my arrival, we seldom had reason to speak: I was a midwesterner, he a southern boy; he was par excellence a naturalist, while I knew nothing about ants, having by then lost all my earlier interest in animal behavior. But the vast museums of Harvard's past glory were not to vanish, and it appeared that Wilson might very well have the intelligence and drive needed to move Harvard's evolutionary tradition into the future.

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 a.s.sembled 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, rea.s.sured 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 cla.s.srooms. So my exams increasingly featured questions that a.s.sessed the plausibility of hypothetical headlines from the New York Times New York Times or or Nature. 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. 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 a.s.sistants 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 a.s.sured of enjoying most of the credit for their efforts. After they came into my lab, generally only a month or two would pa.s.s 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 s.p.u.n.ky 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 a.s.sistants 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 inst.i.tutions do not easily change themselves Most academic battles involve s.p.a.ce 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 a.s.sessment 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.

UPON 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 cla.s.ses were taught by Harvard professors. But with the disappearance of separate cla.s.ses for women, the former cla.s.sroom s.p.a.ce 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 Ma.s.sachusetts 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 pa.s.sing 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 cla.s.s. 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 c.o.c.ktail 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 Ma.s.sachusetts const.i.tuents.

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 a.s.sured 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 s.p.a.ce 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 s.p.a.ce. 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 Ma.s.sachusetts 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 antic.i.p.ated, and Alfred Tissieres 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 a.n.a.lysis, 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. 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. Much more content at their first contacts with molecular biolog