The double helix, p.3

The Double Helix, page 3

 

The Double Helix
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  Snapshot taken at the microbial genetics meeting, held at the Institute for Theoretical Physics, Copenhagen, March 1951. First row: O. Maaløe, R. Latarjet, E. Wollman. Second row: N. Bohr, N. Visconti, G. Ehrensvaard, W. Weidel, H. Hyden, V. Bonifas, G. Stent, H. Kalckar, B. Wright, J. D. Watson, M. Westergaard.

  I thus welcomed Herman’s suggestion that I go that spring to the Zoological Station at Naples, where he had decided to spend the months of April and May. A trip to Naples made great sense. There was no point in doing nothing in Copenhagen, where spring does not exist. On the other hand, the sun of Naples might be conducive to learning something about the biochemistry of the embryonic development of marine animals. It might also be a place where I could quietly read genetics. And when I was tired of it, I might conceivably pick up a biochemistry text. Without any hesitation I wrote to the States requesting permission to accompany Herman to Naples. A cheerful affirmative letter wishing me a pleasant journey came by return post from Washington. Moreover, it enclosed a $200 check for travel expenses. It made me feel slightly dishonest as I set off for the sun.

  4

  MAURICE WILKINS also had not come to Naples for serious science. The trip from London was an unexpected gift from his boss, Professor J. T. Randall. Originally Randall had been scheduled to come to the meeting on macromolecules and give a paper about the work going on in his new biophysics lab. Finding himself overcommitted, he had decided to send Maurice instead. If no one went, it would look bad for his King’s College lab. Lots of scarce Treasury money had to be committed to set up his biophysics show, and suspicions existed that this was money down the drain.

  No one was expected to prepare an elaborate talk for Italian meetings like this one. Such gatherings routinely brought together a small number of invited guests who did not understand Italian and a large number of Italians, almost none of whom understood rapidly spoken English, the only language common to the visitors. The high point of each meeting was the day-long excursion to some scenic house or temple. Thus there was seldom chance for anything but banal remarks.

  By the time Maurice arrived I was noticeably restless and impatient to return north. Herman had completely misled me. For the first six weeks in Naples I was constantly cold. The official temperature is often much less relevant than the absence of central heating. Neither the Zoological Station nor my decaying room atop a six-story nineteenth-century house had any heat. If I had had even the slightest interest in marine animals, I would have done experiments. Moving about doing experiments is much warmer than sitting in the library with one’s feet on a table. At times I stood about nervously while Herman went through the motions of a biochemist, and on several days I even understood what he said. It made no difference, however, whether or not I followed the argument. Genes were never at the center, or even at the periphery, of his thoughts.

  Most of my time I spent walking the streets or reading journal articles from the early days of genetics. Sometimes I daydreamed about discovering the secret of the gene, but not once did I have the faintest trace of a respectable idea. It was thus difficult to avoid the disquieting thought that I was not accomplishing anything. Knowing that I had not come to Naples for work did not make me feel better.

  I retained a slight hope that I might profit from the meeting on the structures of biological macromolecules. Though I knew nothing about the X-ray diffraction techniques that dominated structural analysis, I was optimistic that the spoken arguments would be more comprehensible than the journal articles, which passed over my head. I was specially interested to hear the talk on nucleic acids to be given by Randall. At that time almost nothing was published about the possible three-dimensional configurations of a nucleicacid molecule. Conceivably this fact affected my casual pursuit of chemistry. For why should I get excited learning boring chemical facts as long as the chemists never provided anything incisive about the nucleic acids?

  The odds, however, were against any real revelation then. Much of the talk about the three-dimensional structure of proteins and nucleic acids was hot air. Though this work had been going on for over fifteen years, most if not all of the facts were soft. Ideas put forward with conviction were likely to be the products of wild crystallographers who delighted in being in a field where their ideas could not be easily disproved. Thus, although virtually all biochemists, including Herman, were unable to understand the arguments of the X-ray people, there was little uneasiness. It made no sense to learn complicated mathematical methods in order to follow baloney. As a result, none of my teachers had ever considered the possibility that I might do postdoctoral research with an X-ray crystallographer.

  Maurice, however, did not disappoint me. The fact that he was a substitute for Randall made no difference: I had not known about either. His talk was far from vacuous and stood out sharply from the rest, several of which bore no connection to the purpose of the meeting. Fortunately these were in Italian, and so the obvious boredom of the foreign guests did not need to be construed as impoliteness. Several other speakers were continental biologists, at that time guests at the Zoological Station, who only briefly alluded to macromolecular structure. In contrast, Maurice’s X-ray diffraction picture of DNA was to the point. It was flicked on the screen near the end of his talk. Maurice’s dry English form did not permit enthusiasm as he stated that the picture showed much more detail than previous pictures and could, in fact, be considered as arising from a crystalline substance. And when the structure of DNA was known, we might be in a better position to understand how genes work.

  Suddenly I was excited about chemistry. Before Maurice’s talk I had worried about the possibility that the gene might be fantastically irregular. Now, however, I knew that genes could crystallize; hence they must have a regular structure that could be solved in a straightforward fashion. Immediately I began to wonder whether it would be possible for me to join Wilkins in working on DNA. After the lecture I tried to seek him out. Perhaps he already knew more than his talk had indicated—often if a scientist is not absolutely sure he is correct, he is hesitant to speak in public. But there was no opportunity to talk to him; Maurice had vanished.

  Not until the next day, when all the participants took an excursion to the Greek temples at Paestum, did I get an opportunity to introduce myself. While waiting for the bus I started a conversation and explained how interested I was in DNA. But before I could pump Maurice we had to board, and I joined my sister, Elizabeth, who had just come in from the States. At the temples we all scattered, and before I could corner Maurice again I realized that I might have had a tremendous stroke of good luck. Maurice had noticed that my sister was very pretty, and soon they were eating lunch together. I was immensely pleased. For years I had sullenly watched Elizabeth being pursued by a series of dull nitwits. Suddenly the possibility opened up that her way of life could be changed. No longer did I have to face the certainty that she would end up with a mental defective. Furthermore, if Maurice really liked my sister, it was inevitable that I would become closely associated with his X-ray work on DNA. The fact that Maurice excused himself to go and sit alone did not upset me. He obviously had good manners and assumed that I wished to converse with Elizabeth.

  As soon as we reached Naples, however, my daydreams of glory by association ended. Maurice moved off to his hotel with only a casual nod. Neither the beauty of my sister nor my intense interest in the DNA structure had snared him. Our futures did not seem to be in London. Thus I set off to Copenhagen and the prospect of more biochemistry to avoid.

  5

  I PROCEEDED to forget Maurice, but not his DNA photograph. A potential key to the secret of life was impossible to push out of my mind. The fact that I was unable to interpret it did not bother me. It was certainly better to imagine myself becoming famous than maturing into a stifled academic who had never risked a thought. I was also encouraged by the very exciting rumor that Linus Pauling had partly solved the structure of proteins. The news hit me in Geneva, where I had stopped for several days to talk with the Swiss phage worker Jean Weigle, who was just back from a winter of work at Cal Tech. Before leaving, Jean had gone to the lecture where Linus had made the announcement.

  Pauling’s talk was made with his usual dramatic flair. The words came out as if he had been in show business all his life. A curtain kept his model hidden until near the end of his lecture, when he proudly unveiled his latest creation. Then, with his eyes twinkling, Linus explained the specific characteristics that made his model—the α-helix—uniquely beautiful. This show, like all of his dazzling performances, delighted the younger students in attendance. There was no one like Linus in all the world. The combination of his prodigious mind and his infectious grin was unbeatable. Several fellow professors, however, watched this performance with mixed feelings. Seeing Linus jumping up and down on the demonstration table and moving his arms like a magician about to pull a rabbit out of his shoe made them feel inadequate. If only he had shown a little humility, it would have been so much easier to take! Even if he were to say nonsense, his mesmerized students would never know because of his unquenchable self-confidence. A number of his colleagues quietly waited for the day when he would fall flat on his face by botching something important.

  But Jean could not then tell me whether Linus’ α-helix was right. He was not an X-ray crystallographer and could not judge the model professionally. Several of his younger friends, however, trained in structural chemistry, thought the α-helix looked very pretty. The best guess of Jean’s acquaintances, therefore, was that Linus was right. If so, he had again accomplished a feat of extraordinary significance. He would be the first person to propose something solidly correct about the structure of a biologically important macromolecule. Conceivably, in doing so, he might have come up with a sensational new method which could be extended to the nucleic acids. Jean, however, did not remember any special tricks. The most he could tell me was that a description of the α-helix would soon be published.

  Linus Pauling with his atomic models.

  By the time I was back in Copenhagen, the journal containing Linus’ article had arrived from the States. I quickly read it and immediately reread it. Most of the language was above me, and so I could only get a general impression of his argument. I had no way of judging whether it made sense. The only thing I was sure of was that it was written with style. A few days later the next issue of the journal arrived, this time containing seven more Pauling articles. Again the language was dazzling and full of rhetorical tricks. One article started with the phrase, “Collagen is a very interesting protein.” It inspired me to compose opening lines of the paper I would write about DNA, if I solved its structure. A sentence like “Genes are interesting to geneticists” would distinguish my way of thought from Pauling’s.

  So I began worrying about where I could learn how to solve X-ray diffraction pictures. Cal Tech was not the place—Linus was too great a man to waste his time teaching a mathematically deficient biologist. Neither did I wish to be further put off by Wilkins. This left Cambridge, England, where I knew that someone named Max Perutz was interested in the structure of the large biological molecules, in particular, the protein hemoglobin. I thus wrote to Luria about my newly found passion, asking whether he knew how to arrange my acceptance into the Cambridge lab. Unexpectedly, this was no problem at all. Soon after receiving my letter, Luria went to a small meeting at Ann Arbor, where he met Perutz’ coworker, John Kendrew, then on an extended trip to the States. Most fortunately, Kendrew made a favorable impression on Luria; like Kalckar, he was civilized and in addition supported the Labor Party. Furthermore, the Cambridge lab was understaffed and Kendrew was looking for someone to join him in his study of the protein myoglobin. Luria assured him that I would fit the bill and immediately wrote me the good news.

  It was then early August, just a month before my original fellowship would expire. This meant that I could not long delay writing to Washington about my change of plans. I decided to wait until I was admitted officially into the Cambridge lab. There was always the possibility that something would go wrong. It seemed prudent to put off the awkward letter until I could talk personally with Perutz. Then I could state in much greater detail what I might hope to accomplish in England. I did not, however, leave at once. Again I was back in the lab, and the experiments I was doing were fun, in a second-class fashion. Even more important, I did not want to be away during the forthcoming International Poliomyelitis Conference, which was to bring several phage workers to Copenhagen. Max Delbrück was in the expected group, and since he was a professor at Cal Tech he might have further news about Pauling’s latest trick.

  Delbrück, however, did not enlighten me further. The α-helix, even if correct, had not provided any biological insights; he seemed bored speaking about it. Even my information that a pretty X-ray photograph of DNA existed elicited no real response. But I had no opportunity to be depressed by Delbrück’s characteristic bluntness, for the poliomyelitis congress was an unparalleled success. From the moment the several hundred delegates arrived, a profusion of free champagne, partly provided by American dollars, was available to loosen international barriers. Each night for a week there were receptions, dinners, and midnight trips to waterfront bars. It was my first experience with the high life, associated in my mind with decaying European aristocracy. An important truth was slowly entering my head: a scientist’s life might be interesting socially as well as intellectually. I went off to England in excellent spirits.

  6

  MAX PERUTZ was in his office when I showed up just after lunch. John Kendrew was still in the States, but my arrival was not unexpected. A brief letter from John said that an American biologist might work with him during the following year. I explained that I was ignorant of how X rays diffract, but Max immediately put me at ease. I was assured that no high-powered mathematics would be required: both he and John had studied chemistry as undergraduates. All I need do was read a crystallographic text; this would enable me to understand enough theory to begin to take X-ray photographs. As an example, Max told me about his simple idea for testing Pauling’s α-helix. Only a day had been required to get the crucial photograph confirming Pauling’s prediction. I did not follow Max at all. I was even ignorant of Bragg’s Law, the most basic of all crystallographic ideas.

  We then went for a walk to look over possible digs for the coming year. When Max realized that I had come directly to the lab from the station and had not yet seen any of the colleges, he altered our course to take me through King’s, along the backs, and through to the Great Court of Trinity. I had never seen such beautiful buildings in all my life, and any hesitation I might have had about leaving my safe life as a biologist vanished. Thus I was only nominally depressed when I peered inside several damp houses known to contain student rooms. I knew from the novels of Dickens that I would not suffer a fate the English denied themselves. In fact, I thought myself very lucky when I found a room in a two-story house on Jesus Green, a superb location less than ten minutes’ walk from the lab.

  The following morning I went back to the Cavendish, since Max wanted me to meet Sir Lawrence Bragg. When Max telephoned upstairs that I was here, Sir Lawrence came down from his office, let me say a few words, and then retired for a private conversation with Max. A few minutes later they emerged to allow Bragg to give me his formal permission to work under his direction. The performance was uncompromisingly British, and I quietly concluded that the white-mustached figure of Bragg now spent most of its days sitting in London clubs like the Athenaeum.

  The thought never occurred to me then that later on I would have contact with this apparent curiosity out of the past. Despite his indisputable reputation, Bragg had worked out his Law just before World War I, so I assumed he must be in effective retirement and would never care about genes. I politely thanked Sir Lawrence for accepting me and told Max I would be back in three weeks for the start of the Michaelmas term. I then returned to Copenhagen to collect my few clothes and to tell Herman about my good luck in being able to become a crystallographer.

  Herman was splendidly cooperative. A letter was dispatched telling the Fellowship Office in Washington that he enthusiastically endorsed my change in plans. At the same time I wrote a letter to Washington, breaking the news that my current experiments on the biochemistry of virus reproduction were at best interesting in a nonprofound way. I wanted to give up conventional biochemistry, which I believed incapable of telling us how genes work. Instead I told them that I now knew that X-ray crystallography was the key to genetics. I requested the approval of my plans to transfer to Cambridge so that I might work at Perutz’ lab and learn how to do crystallographic research.

  I saw no point in remaining in Copenhagen until permission came. It would have been absurd to stay there wasting my time. The week before, Maaløe had departed for a year at Cal Tech, and my interest in Herman’s type of biochemistry remained zero. Leaving Copenhagen was of course illegal in the formal sense. On the other hand, my request could not be refused. Everyone knew of Herman’s unsettled state, and the Washington office must have been wondering how long I would care to remain in Copenhagen. Writing directly about Herman’s absence from his lab would have been not only ungentlemanly but unnecessary.

 

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