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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 three-dimensional 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 100 years would pass 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 crevasses 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 of analyzing x-ray diagrams was far from straightforward. Given Pauling’s recent success using molecular modeling to find the alpha helix, using this approach on DNA was far from outlandish; actually, it was a no-brainer.

2) Only work on problems 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 only feel comfortable taking on a problem when I feel meaningful results can come over a three- to five-year interval. Risking your career on problems when you have only a tiny chance of seeing the 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, 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 lustrous department. By the early 1950s, Linus Pauling’s scientific interactions with fellow scientists were effectively monologues instead of dialogues. He wanted adoration, not criticism.

4) Stay in close contact with your intellectual competitors

In pursuing an important objective, you must expect serious competition. 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 competitors is an assurance 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 competitors 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 competition. The smaller the field, the better you can size it up, and the better the chance you will run an intelligent race.

Avoiding your competition 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 competitor 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 his or her 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 to also 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 having kept good relations with others in the field outside our partnership, he would always have his ideas checked by others with even more 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 assertion 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, that the stereochemistry of the sugar-phosphate groups would of course move them to outer positions of helices that use approximately 10 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 person 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 assign 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 come to nothing if my phage-day patrons, Salvador Luria and Max Delbrück, 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, Delbrück arranged a National Foundation for Poliomyelitis fellowship for the succeeding year. In finding the funds that kept me in Cambridge, Luria and Delbrück were hoping that my new career as a biological structural chemist would be successful 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, you should never burn your past intellectual bridges, at least until your new career has taken off.

James Watson’s Avoid Boring People: And Other Lessons from a Life in Science will be published by Knopf in September.

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Tagged: Biomedicine

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