by James Watson
At the State Serum Institute in Copenhagen, 1951. Günther Stent is on the far left, Ole Maaloe is third from left, Niels feme is standing, and I am sitting in front of Niels.
I would have considered such acculturation alone ample justification for my spending two months in Italy, but a small, high-level meeting on macromolecular structure in the Zoological Station auditorium provided an even better excuse. Until that mid-May gathering in Naples, I had assumed no one would soon understand the detailed, three-dimensional structure of DNA at the atomic level. Since genetic information, which was encoded within DNA, varied, each different DNA molecule most likely presented a different structure to solve. But my pessimism, born of chemical naivete, lifted dramatically after a talk by the youngish King's College London physicist Maurice Wilkins. Instead of revealing disorganized DNA molecules, DNA in his X-ray diffraction pictures was yielding patterns consistent with crystalline assemblies. Later he told me that the DNA structure might not be that difficult to solve since it was a polymeric molecule made up from only four different building blocks. If he was right, the essence of the gene would emerge not from the genetic approaches of the phage group but from the methodologies of the X-ray crystallographer.
Despite my obvious excitement at his results, Maurice did not seem to judge me a useful future collaborator. So upon arriving back in Copenhagen, I wrote Salva seeking help in finding another biologically oriented crystallographic lab in which I could learn the basic methodologies of the structural chemist. Salva delivered after a meeting in Ann Arbor at which he met the Cambridge University protein crystallographer John Kendrew. Then just thirty-four, John was seeking an even younger scientist to join him. With Salva having spoken well of my abilities, he agreed to my coming aboard to learn crystallographic methodologies from him and his colleagues at the recently established Medical Research Council (MRC) Unit for the Study of Structure of Biological Systems.
By then I was again studying the transmission of radioactive labels from parental to progeny phages, knowing that early in September Max Delbrück was coming to Copenhagen for an international poliomyelitis conference. When his ship arrived, Günther, Ole, and I went to the Copenhagen dock to greet Max with a large poster saying “Velkommen Max Mendelian Mater.” The congress itself was a routine affair except for dinner at Niels Bohr's home within the Carlsberg Brewery. Its founder had long before arranged that his opulent domicile should always be occupied by Denmark's preeminent citizen. Luckily, I was not seated near Bohr, who was likely to be expressing thoughts that no one around him, Danish or foreign, could understand.
Soon I was in England to meet John Kendrew's coworker Max Perutz, to make preparations for my coming to Cambridge in early October. Though John was still in the States, my meeting with Perutz and his boss, the Cavendish Professor of Physics, Sir Lawrence Bragg, went well and I took that night's train to Edinburgh for a two-day peek at the Scottish Highlands near Oban. In returning by train to London, I was engrossed in Evelyn Waugh's Brideshead Revisited. Delbrück was ending his European trip with visits to André Lwoff and Jacques Monod at the Institut Pasteur, and so from London I flew to Paris. There on a Sunday afternoon, after watching Monod nimbly scale the big boulders in the woods at nearby Fontainebleau, I said goodbye to Max as he boarded a plane at Orly Though Max was highly skeptical of my foray into a Pauling-like structural chemistry, he did not choose this occasion to say so. Instead he wished me well and I felt the creeping apprehension of knowing that I would no longer be part of the world in which grace and the fall from it could be comfortably predicted by asking, “What will Max say?” Soon I would be somewhere he did not matter.
Max Delbrück arrives in Copenhagen, September 1951. From left: Günther Stent, Ole Maaloe, Carsten Bresch, and Jim Watson
Remembered Lessons
1. Have a big objective that makes you feel special
No one within the phage group of 1950 would have denied our air of self-importance or our sense of being a happy few. The disciples of George Beadle and Ed Tatum working with Neurospora on gene-enzyme connections never came together with such esprit de corps. Max Delbrück's personality was a big factor. His reverence for deep truths and commitment to sharing them unselfishly was saint-like. But these virtues attend many uninspired minds as well and were never the key to the fervor of his acolytes. Instead it was his great commission that we go to the heart of the gene, in search of its genetic and molecular essences. To obssess over less fundamental goals made no sense to Max. Phages, being virtually naked genes that yielded answers after only a night's sleep, had to be the best biological tools for moving forward fast. Legions of graduate students across biology were pursuing things worth knowing but perhaps not worth devoting one's life to. The quest for such an unrivaled prize of indisputable significance fired in our imaginations a devotion such as religion fires in others', but without the irrationality.
2. Sit in the front row when a seminar's title intrigues you
By far the best way to profit from seminars that interest you is to sit in the front row. Not being bored, you do not risk the embarrassment of falling asleep in front of everybody's eyes. If you cannot follow the speaker's train of thought from where you are, you are in a good place to interrupt. Chances are you are not alone in being lost and most everyone in the audience will silently applaud. Your prodding may in fact reveal whether the speaker indeed has a take-home message or has simply deluded himself into believing he does. Waiting until a seminar is over to ask questions is pathologically polite. You will probably forget where you got lost and start questioning results you actually understood.
Now, if you have suspicions that a seminar will bore you but are not sure enough to risk skipping it, sit in the back row. There a dull, glazed expression will not be conspicuous, and if you walk out, your departure may be thought temporary and compelled by the call of nature. Szilard did not follow this advice, habitually sitting in a front row and getting up abruptly in the middle of talks when he'd had too much of too little. Those outside his close circle of friends were relieved when his inherent restlessness made him move on to a potentially more exciting domicile.
3. Irreproducible results can be blessings in disguise
A desired result in science is gratifying, but there is no contentment until you have repeated your experiments several times and got the same answer. AI Hershey called such moments of satisfaction “Her-shey heaven.” Just the opposite feeling of maddening inferno comes from irreproducible results. Albert Keiner and Renato Dulbecco felt it before they found that visible light can reverse much UV damage. Del-briick, struck by how long this phenomenon remained undiscovered, put it down to fastidiousness. He described what he called “the principle of limited sloppiness.” If you are too sloppy, of course you never get reproducible results. But if you are just a little sloppy, you have a good chance of introducing an unsuspected variable and possibly nailing down an important new phenomenon. In contrast, always doing an experiment in precisely the same way limits you to exploring conditions that you already suspect might influence your experimental results. Before the Kelner-Dulbecco observations, no one had cause to suspect that under any conditions visible light could reverse the effects of UV irradiation. Great inspirations are often accidents.
4. Always have an audience for your experiments
Before starting an experiment, be sure others are interested in the premise. Mindless minor variations on prior good science will generate yawns in the world beyond your lab. Though such almost repetitive motions are good ways for students to learn lab techniques, they should be seen as exercises and not as real science, with their results publishable only in journals that hotshot scientists never read. Now, trying to break new ground may lead to consequences that seem worse than yawns, and you must be prepared for most of your peers to think you are out of your mind. If, however, you cannot think of at least one and preferably several bright individuals who can take appreciative notice of what you are doing, your tenacity may very w
ell indicate that you are either stupid or crazy.
5. Avoid boring people
Social gatherings of even successful academics are no different from gatherings of any professional cohort. The truly interesting are inevitably a small subset of any group. Don't be surprised when arriving at some senior colleague's house for dinner if you feel an unexplainable desire to leave when you learn whom you're seated next to. Routinely reading the New York Times at breakfast will expose you to many more facts and ideas than you are ever likely to acquire during evenings with individuals who in most instances haven't had to think differently since getting tenure. Unless you have reason to anticipate a very good meal or the presence of a fetching face, take care not to accept outright any invitations to senior faculty's homes. Leave open the possibility that a sixteen-hour experiment might keep you from coming. If you later find out that someone you want to meet will be there, make known your sudden availability and come gallantly with a small box of chocolates to enjoy with the coffee.
6. Science is highly social
In high school there is a domain of facts and ideas in which you can succeed separate from the world of hanging out with your peers. Once you get into science, however, worlds collide, and not only your fun but also your professional success demands you know as much about your peers’ personality quirks as you do about their experiments. Gossip is a fact of life also among scientists, and if you are out of the loop of what's new you are working with one hand tied behind your back. The intellectual vitality of the phage group drew not only from its meetings but also from constant visits to one another's labs, often for joint experiments. Particularly at the start of your career, you should seize any chance to see how other labs function and talk about results that might be interpreted in new ways. It's all too natural when young to see one's peers merely as competitors. Some ofthat is necessary and appropriate, but scientific knowledge is not a zero-sum game: there is always something more to be discovered, and getting to know your colleagues can only help you get a piece of the prize.
7. Leave a research field before it bores you
When I decided to abandon the genetic approach of the phage group in favor of learning X-ray crystallography to go after the three-dimensional structure of DNA in Cambridge, I was in no way bored with the work of Max Delbrück and Salva Luria. My last phage experiments in Copenhagen were still very rewarding. By then, however, I was more and more drawn to finding the DNA structure, and meeting Wilkins gave me good reason to believe the phage group, for all its high purpose, was not the way. In science, as in other professions and in personal involvements, individuals too often wait for abject misery before effecting change that makes perfect sense. In fact, there is no good reason ever to be on the downward slope of experience. Avoid it and you'll still be enjoying life when you die.
6. MANNERS NEEDED FOR IMPORTANT SCIENCE
I ARRIVED in Cambridge in the fall of 1951 sensing a majesty of place and intellectual style unmatched anywhere in the world. Its great university, reflecting almost nine hundred years of English history, first centered itself along the banks of the river Cam, whose modest waters move northeast across East Anglia to the market city of Ely. There its massive twelfth-century cathedral had long towered over the vast flat fenland marshes that emptied into the Cam forty miles from the shallow waters of the Wash, over which tidal waters from the North Sea still roar twice daily. It was the draining of the fens over many centuries that created the rich agricultural fields and wealth of the great East Anglia estate owners. Their benefactions in return helped create along the “backs” of the Cam the many elegant student residences, dining halls, and chapels that already many centuries ago marked out Cambridge as a market city of extraordinary grace and beauty.
For most of its history, Cambridge University was highly decentralized, with the teaching exclusively carried out by its residential colleges, among which Trinity was long the grandest, having enjoyed the matchless patronage of Henry Vili. In a room off the Great Court had lived the young Newton, whose greatest science was done in his twenties and thirties before he went up to London to be master of the mint.
Until the mid-eighteenth century, the primary role of the colleges was to educate clergy for the Church of England, the mission carried out by fellows (dons) who were themselves required to remain unmarried while part of college life. Only in the nineteenth century did scienee become an important part of the Cambridge teaching scene. Charles Darwin's serious excitement about natural history and geology came from his exposure in the early 1830s to these disciplines at Christ's College. Over the next half century, the responsibility for instruction increasingly shifted away from the colleges to newly created academic departments under university control. In 1871, the Duke of Devonshire, Henry Cavendish, donated funds for the creation of the Cavendish Laboratory and the appointment as the first Cavendish Professor of James Clerk Maxwell, whose eponymous equations first unified the dynamics of electricity and magnetism. Upon Maxwell's early death at age forty-nine in 1879, the twenty-nine-year-old John William Strutt (Lord Rayleigh), famed for his ideas on optics, became the second Cavendish Professor of Physics. In 1904, he was to win a Nobel Prize, as would the next four successors to the chair: J. J. Thomson (1906), Ernest Rutherford (1908), William Lawrence Bragg (1915), and Nevill Mott (1977).
By the start of the twentieth century, Cambridge stood out as one of the world's leading centers for science, of the same rank as the best German universities—Heidelberg, Göttingen, Berlin, and Munich. Over the next fifty years, Cambridge would remain in that rarefied league, but Germany's place would be supplanted by the United States, much strengthened by its absorption of many of the better Jewish scientists forced to flee Hitler. England similarly much benefited from the arrival of some extraordinary Jewish intellectuals. If Max Perutz had not had the good sense to leave Austria in 1936 as a young chemist, there would have then been no reason for my now moving along the Cam.
Though winning the great struggle against Hitler had drained England financially, the country's intellectuals took pleasure in knowing that their country's great victory was much of their own making. Without the physicists who provided radar for British aviators during the Battle of Britain, or the Enigma code breakers of Bletchley Park who successfully pinpointed the German U-boats assaulting the Allies’ Atlantic convoys, things might have turned out very differently.
Emboldened by the war to think boldly, the then tiny Medical Research Council (MRC) unit for the Study of Structure of Biological Systems was doing science in the early 1950s that most chemists and biologists thought ahead of its time. Using X-ray crystallography to establish the 3-D structure of proteins was likely to be orders of magnitude more difficult than solving the structures of small molecules such as penicillin. Proteins were daunting objectives, not only because of their size and irregularity but because the sequence of the amino acids along their polypeptide chains was still unknown. This obstacle, however, was soon likely to be overcome. The biochemist Fred Sanger, working less than half a mile away from Max Perutz and John Kendrew at the MRC lab, was far along the path to establish the amino acid sequences of the two insulin polypeptides. Others following in his steps would soon be working out the amino acid sequences of many other proteins.
Polypeptide chains within proteins were then thought to have a mixture of regularly folded helical and ribboned sections intermixed with irregularly arranged blocks of amino acids. Less than a year before, the nature of the putative helical folds was still not settled, with the Cambridge trio of Perutz, Kendrew, and Bragg hoping to find their way by building Tinkertoy-like, 3-D models of helically folded polypeptide chains. Unfortunately, they received a local chemist's bad advice about the conformation of the peptide bond and, in late 1950, published a paper soon shown to be incorrect. Within months they were upstaged by Caltech's Linus Pauling, then widely regarded as the world's best chemist. Through structural studies on dipeptides, Pauling inferred that peptide bonds have strictly planar
configurations and, in April 1951, he revealed to much fanfare the stereochemically pleasing a-helix. Though Cambridge was momentarily stunned, Max Perutz quickly responded using a clever crystallographic insight to show that the chemically synthesized polypeptide, polybenzylgluta-mate, took up the a-helical conformation. Again the Cavendish group could view itself as a major player in protein crystallography.
The unit's resident theoretician was by then the physicist Francis Crick, who at thirty-five was two years younger than Max Perutz and one year older than John Kendrew. Francis was of middle-class, nonconformist, Midlands background, though his father's long-prosperous shoe factories in Northampton failed during the Great Depression of the 1930s. It was only with the help of a scholarship from Northampton Grammar School that Francis moved to the Mill Hill School in North London, where his father and uncle had gone. There he liked science but never pulled out the grades required for Oxford or Cambridge. Instead he studied physics at University College London, afterward staying on for a Ph.D. financially sponsored by his uncle Arthur, who after Mill Hill had chosen to open an antacid-dispensing pharmacy instead of joining the family shoe business.
