"The Double Helix: A Personal Account of the Discovery of the Structure of DNA" ~ James D. Watson (Part 1 of 2)
Preface
HERE I relate my version of how the structure of DNA was discovered. In doing so I have tried to catch the atmosphere of the early postwar years in England, where most of the important events occurred. As I hope this book will show, science seldom proceeds in the straightforward logical manner imagined by outsiders. Instead, its steps forward (and sometimes backward) are often very human events in which personalities and cultura1 traditions play major roles. To this end I have attempted to recreate my first impressions of the relevant events and personalities rather than present an assessment which takes into account the many facts I have learned since the structure was found. Although the latter approach might be more objective, it would fail to convey the spirit of an adventure characterized both by youthful arrogance and by the belief that the truth, once found, would be simple as well as pretty. Thus many of the comments may seem one-sided and unfair, but this is often the case in the incomplete and hurried way in which human beings frequently decide to like or dislike a new idea or acquaintance. In any event, this account represents the way I saw things then, in 1951-1953: the ideas, the people, and myself.
I am aware that the other participants in this story would tell parts of it in other ways, sometimes because their memory of what happened differs from mine and, perhaps in even more cases, because no two people ever see the same events in exactly the same light. In this sense, no one will ever be able to write a definitive history of how the structure was established. Nonetheless, I feel the story should be told, partly because many of my scientific friends have expressed curiosity about how the double helix was found, and to them an incomplete version is better than none. But even more important, I believe, there remains general ignorance about how science is "done." That is not to say that all science is done in the manner described here. This is far from the case, for styles of scientific research vary almost as much as human personalities. On the other hand, I do not believe that the way DNA came out constitutes an odd exception to a scientific world complicated by the contradictory pulls of ambition and the sense of fair play. The thought that I should write this book has been with me almost from the moment the double helix was found. Thus my memory of many of the significant events is much more complete than that of most other episodes in my life. I also have made extensive use of letters Written at virtually weekly intervals to my parents. These were especially helpful in exactly dating a number of the incidents. Equally important have been the valuable comments by various friends who kindly read earlier versions and gave in some instances quite detailed accounts of incidents that I had referred to in less complete form. To be sure, there are cases where my recollections differ from theirs, and so this book must be regarded as my view of the matter.
IN THE summer of 1955, I arranged to join some friends who were going into the Alps. Alfred Tissieres, then a Fellow at King's, had said he would get me to the top of the Rothorn, and even though I panic at voids this did not seem to be the time to be a coward. So after getting in shape by letting a guide lead me up the Allinin, I took the two-hour postal bus trip to Zinal, hoping that the driver was not carsick as he lurched the bus around the narrow road twisting above the falling rock slopes. Then I saw Alfred standing in front of the hotel, talking with a long-mustached Trinity don who had been in India during the war. Since Alfred was still out of training, we decided to spend the afternoon walking up to a small restaurant which lay at the base of the huge glacier falling down off the Obergabelhorn and over which we were to walk the next day. We were only a few minutes out of sight of the hotel when we saw a party coming down upon us, and I quickly recognized one of the climbers. He was Willy Seeds, a scientist who several years before had worked at King's College, London, with Maurice Wilkins on the optical properties of DNA fibers. Willy soon spotted me, slowed down, and momentarily gave the impression that he might remove his rucksack and chat for a while. But all he said was, "How's Honest Jim?" and quickly increasing his pace was soon below me on the path. Later as I trudged upward, I thought again about our earlier meetings in London. Then DNA was still a mystery, up for grabs, and no one was sure who would get it and whether he would deserve it if it proved as exciting as we semisecretly believed. But now the race was over and, as one of the winners, I knew the tale was not simple and certainly not as the newspapers reported. Chiefly it was a matter of five people: Maurice Wilkins, Rosalind Franklin, Linus Pauling, Francis Crick, and me. And as Francis was the dominant force in shaping my part, I will start the story with him.
I am aware that the other participants in this story would tell parts of it in other ways, sometimes because their memory of what happened differs from mine and, perhaps in even more cases, because no two people ever see the same events in exactly the same light. In this sense, no one will ever be able to write a definitive history of how the structure was established. Nonetheless, I feel the story should be told, partly because many of my scientific friends have expressed curiosity about how the double helix was found, and to them an incomplete version is better than none. But even more important, I believe, there remains general ignorance about how science is "done." That is not to say that all science is done in the manner described here. This is far from the case, for styles of scientific research vary almost as much as human personalities. On the other hand, I do not believe that the way DNA came out constitutes an odd exception to a scientific world complicated by the contradictory pulls of ambition and the sense of fair play. The thought that I should write this book has been with me almost from the moment the double helix was found. Thus my memory of many of the significant events is much more complete than that of most other episodes in my life. I also have made extensive use of letters Written at virtually weekly intervals to my parents. These were especially helpful in exactly dating a number of the incidents. Equally important have been the valuable comments by various friends who kindly read earlier versions and gave in some instances quite detailed accounts of incidents that I had referred to in less complete form. To be sure, there are cases where my recollections differ from theirs, and so this book must be regarded as my view of the matter.
IN THE summer of 1955, I arranged to join some friends who were going into the Alps. Alfred Tissieres, then a Fellow at King's, had said he would get me to the top of the Rothorn, and even though I panic at voids this did not seem to be the time to be a coward. So after getting in shape by letting a guide lead me up the Allinin, I took the two-hour postal bus trip to Zinal, hoping that the driver was not carsick as he lurched the bus around the narrow road twisting above the falling rock slopes. Then I saw Alfred standing in front of the hotel, talking with a long-mustached Trinity don who had been in India during the war. Since Alfred was still out of training, we decided to spend the afternoon walking up to a small restaurant which lay at the base of the huge glacier falling down off the Obergabelhorn and over which we were to walk the next day. We were only a few minutes out of sight of the hotel when we saw a party coming down upon us, and I quickly recognized one of the climbers. He was Willy Seeds, a scientist who several years before had worked at King's College, London, with Maurice Wilkins on the optical properties of DNA fibers. Willy soon spotted me, slowed down, and momentarily gave the impression that he might remove his rucksack and chat for a while. But all he said was, "How's Honest Jim?" and quickly increasing his pace was soon below me on the path. Later as I trudged upward, I thought again about our earlier meetings in London. Then DNA was still a mystery, up for grabs, and no one was sure who would get it and whether he would deserve it if it proved as exciting as we semisecretly believed. But now the race was over and, as one of the winners, I knew the tale was not simple and certainly not as the newspapers reported. Chiefly it was a matter of five people: Maurice Wilkins, Rosalind Franklin, Linus Pauling, Francis Crick, and me. And as Francis was the dominant force in shaping my part, I will start the story with him.
1.
I HAVE never seen Francis Crick in a modest mood. Perhaps in other company he is that way, but I have never had reason so to judge him. It has nothing to do with his present fame. Already he is much talked about, usually with reverence, and someday he may be considered in the category of Rutherford or Bohr. But this was not true when, in the fall of 1951, I came to the Cavendish Laboratory of Cambridge University to join a small group of physicists and chemists working on the three-dimensional structures of proteins. At that time he was thirty-five, yet almost totally unknown. Although some of his closest colleagues realized the value of his quick, penetrating mind and frequently sought his advice, he was often not appreciated, and most people thought he talked too much. Leading the unit to which Francis belonged was Max Perutz, an Austrian-born chemist who came to England in 1936. He had been collecting X-ray diffraction data from hemoglobin crystals for over ten years and was just beginning to get somewhere. Helping him was Sir Lawrence Bragg, the director of the Cavendish. For almost forty years Bragg, a Nobel Prize winner and one of the founders of crystallography, had been watching X-ray diffraction methods solve structures of everincreasing difficulty.* The more complex the molecule, the happier Bragg became when a new method allowed its elucidation.
Thus in the immediate postwar years he was especially keen about the possibility of solving the structures of proteins, the most complicated of all molecules. Often, when administrative duties permitted, he visited Perutz' office to discuss recently accumulated X-ray data. Then he would return home to see if he could interpret them. Somewhere between Bragg the theorist and Perutz the experimentalist was Francis, who occasionally did experiments but more often was immersed in the theories for solving protein structures. Often he came up with something novel, would become enormously excited, and immediately tell it to anyone who would listen. A day or so later he would often realize that his theory did not work and return to experiments, until boredom generated a new attack on theory. There was much drama connected with these ideas. They did a great deal to liven up the atmosphere of the lab, where experiments usually lasted several months to years. This came partly from the volume of Crick's voice he talked louder and faster than anyone else and, when he laughed, his location within the Cavendish was obvious. Almost everyone enjoyed these manic moments, especially when we had the time to listen attentively and to tell him bluntly when we lost the train of his argument. But there was one notable exception. Conversations with Crick frequently upset Sir Lawrence Bragg, and the h sound of his voice was often sufficient to make Bragg move to a safer room. Only infrequently would he come to tea in the Cavendish, since it meant enduring Crick's booming over the tea room. Even then Bragg was not completely safe. On two occasions the corridor outside his office was flooded with water pouring out of a laboratory in which Crick was working. Francis, with his interest in theory, had neglected to fasten securely the rubber tubing around his suction pump.
Thus in the immediate postwar years he was especially keen about the possibility of solving the structures of proteins, the most complicated of all molecules. Often, when administrative duties permitted, he visited Perutz' office to discuss recently accumulated X-ray data. Then he would return home to see if he could interpret them. Somewhere between Bragg the theorist and Perutz the experimentalist was Francis, who occasionally did experiments but more often was immersed in the theories for solving protein structures. Often he came up with something novel, would become enormously excited, and immediately tell it to anyone who would listen. A day or so later he would often realize that his theory did not work and return to experiments, until boredom generated a new attack on theory. There was much drama connected with these ideas. They did a great deal to liven up the atmosphere of the lab, where experiments usually lasted several months to years. This came partly from the volume of Crick's voice he talked louder and faster than anyone else and, when he laughed, his location within the Cavendish was obvious. Almost everyone enjoyed these manic moments, especially when we had the time to listen attentively and to tell him bluntly when we lost the train of his argument. But there was one notable exception. Conversations with Crick frequently upset Sir Lawrence Bragg, and the h sound of his voice was often sufficient to make Bragg move to a safer room. Only infrequently would he come to tea in the Cavendish, since it meant enduring Crick's booming over the tea room. Even then Bragg was not completely safe. On two occasions the corridor outside his office was flooded with water pouring out of a laboratory in which Crick was working. Francis, with his interest in theory, had neglected to fasten securely the rubber tubing around his suction pump.
At the time of my arrival, Francis' theories spread far, beyond the confines of protein crystallography. Anything important would attract him, and. he frequently visited other labs to see which new experiments had been done. Though he was generally polite and considerate of colleagues who did not realize the real meaning of their latest experiments, he would never hide this fact from them. Almost immediately he would suggest a rash of new experiments that should confirm his interpretation. Moreover, he would not refrain from subsequently telling all who would listen how his clever new idea might set science ahead. As a result, there existed an unspoken yet real fear of Crick, especially among his contemporaries who had yet to establish their reputations. The quick manner in which he seized their facts and tried to reduce them to coherent patterns frequently made his friends' stomachs sink with the apprehension that, all too often in the near future, he would succeed, and expose to the world the fuzziness of minds hidden from direct view by the considerate, well-spoken manners of the Cambridge colleges.
Though he had dining rights for one meal a week at Caius College, he was not yet a fellow of any college. Partly this was his own choice. Clearly he did not want to be burdened by the unnecessary sight of undergraduate tutees. Also a factor was his laugh, against which many dons would most certainly rebel if subjected to its shattering bang more than once a week. I am sure this occasionally bothered Francis, even though he obviously knew that most High Table life is dominated by pedantic, middle aged men incapable of either amusing or educating him in anything worthwhile. There always existed King's College, opulently nonconformist and clearly capable of absorbing him without any loss of his or its character. But despite much effort on the part of his friends, who knew he was a delightful dinner companion, they were never able to hide the fact that a stray remark over sherry might bring Francis smack into your life.
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| Mesopotamian Anunnaki and Tree of Life |
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| Nammu and the Tree of Life at Ur |
2.
BEFORE my arrival in Cambridge, Francis only occasionally thought about deoxyribonucleic acid (DNA) and its role in heredity. This was not because he thought it uninteresting. Quite the contrary. A major factor in his leaving physics and developing an interest in biology had been the reading in 1946 of What Is Life? by the noted theoretical physicist Erwin Schrodinger. This book very elegantly propounded the belief that genes were the key components of living cells and that, to understand what life is, we must know how genes act. When Schrodinger wrote his book (1944) there was general acceptance that genes were special types of protein molecules. But almost at this same time the bacteriologist 0. T. Avery was carrying out experiments at the Rockefeller Institute in New York which showed that hereditary traits could be transmitted from one bacterial cell to another by purified DNA molecules.
Given the fact that DNA was known to occur in the chromosomes of all cells, Avery's experiments strongly suggested that future experiments would show that all genes were composed of DNA. If true, this meant to Francis that proteins would not be the Rosetta Stone for unravelling the true secret of life. Instead, DNA would have to provide the key to enable us to find out how the genes determined, among other characteristics, the color of our hair, our eyes, most likely our comparative intelligence, and maybe even our potential to amuse others.
Of course there were scientists who thought the evidence favoring DNA was inconclusive and preferred to believe that genes were protein molecules. Francis, however, did not worry about these skeptics. Many were cantankerous fools who unfailingly backed the wrong horses. One could not be a successful scientist without realizing that, in contrast to the popular conception supported by newspapers and mothers of scientists, a goodly number of. scientists are not only narrowminded and dull, but also just stupid.
Francis, nonetheless, was not then prepared to jump into the DNA world. Its basic importance did not seem sufficient cause by itself to lead him out of the protein field which he had worked in only two years and was just beginning to master intellectually. In addition, his colleagues at the Cavendish were only marginally interested in the nucleic acids, and even in the best of financial circumstances it would take two or three years to set up a new research group primarily devoted to using X rays to look at the DNA structure.
Moreover, such a decision would create an awkward personal situation. At this time molecular work on DNA in England was, for all practical purposes, the personal property of Maurice Wilkins, a bachelor who worked in London at King's College* Like Francis, Maurice had been a physicist and also used X-ray diffraction as his principal tool of research. It would have looked very bad if Francis had jumped in on a problem that Maurice had worked over for several years. The matter was even worse because the two, almost equal in age, knew each other and, before Francis remarried, had frequently met for lunch or dinner to talk about science.
It would have been much easier if they had been living in different countries. The combination of England's coziness – all the important people, if not related by marriage, seemed to know one another plus the English I sense of fair play would not allow Francis to move in on Maurice's problem. In France, where fair play obviously did not exist, these problems would not have arisen. The States also would not have permitted such a situation to develop. One would not expect someone at Berkeley to ignore first-rate problem merely because someone at Cal Tech had started first. In England, however, it simply l would not look right.
Even worse, Maurice continually frustrated Francis by never seeming enthusiastic enough about DNA. He appeared to enjoy slowly understating important arguments. It was not a question of intelligence or common sense Maurice clearly had both; witness his seizing DNA before almost everyone else. It was that Francis felt he could never get the message over to Maurice that you did not move cautiously when you were holding dynamite like DNA. Moreover, it was increasingly difficult to take Maurice's mind off his assistant, Rosalind Franklin.
Not that he was at all in love with Rosy, as we called her from a distance. Just the opposite a1most from the moment she arrived in Maurice's lab, they began to upset each other. Maurice, a beginner in X-ray diffraction work, wanted some professional help and hoped that Rosy, a trained crystallographer, could speed up his research. Rosy, however, did not see the situation this way. She claimed that she had been given DNA for her own problem and would not think of herself as Maurice's assistant.
I suspect that in the beginning Maurice hoped that Rosy would calm down. Yet mere inspection suggested that she would not easily bend. By choice she did not emphasize her feminine qualities. Though her features were strong, she was not unattractive and might have been quite stunning had she taken even a mild interest in clothes. This she did not. There was never lipstick to contrast with her straight black hair, while at the age of thirty-one her dresses showed all the imagination of English bluestocking adolescents. So it was quite easy to imagine her the product of an unsatisfied mother who unduly stressed the desirability of professional careers that it could save bright girls from marriages to dull men. But this was not the case. Her dedicated, austere life could not be thus explained she was the daughter of a solidly comfortable, erudite banking family.
Clearly Rosy had to go or be put in her place. The former was obviously preferable because, given her belligerent moods, it would be very difficult for Maurice to maintain a dominant position that would allow him to think unhindered about DNA. Not that at times he didn't see, some reason for her complaints – King's had two combination rooms, one for men, the other for women, certainly a thing of the past. But he was not responsible, and it was no pleasure to bear the cross for the added barb that the women's combination room remained dingily pokey whereas money had been spent to make life agreeable for him and his friends when they had their morning coffee.
Unfortunately, Maurice could not see any decent way to give Rosy the boot. To start with, she had been given to think that she had a position for several years. Also, there was no denying she had a good brain. If she could only keep her emotions under control, there would be a good chance that she could really help him. But merely wishing for relations to improve was taking something of a gamble, for Cal Tech's fabulous chemist Linus Pauling was not subject to the confines of British fair play. Sooner or later Linus, who had just turned fifty, was bound to try for the most important of an scientific prizes. There was no doubt that he was interested. Our first principles told us that Pauling could not be the greatest of all chemists without realizing that DNA was the most golden of all molecules. Moreover, there was definite proof. Maurice had received a letter from Linus asking for a copy of the crystalline DNA X-ray photographs. After some hesitation he wrote back saying that he wanted to look more closely at the data before releasing the pictures. All this was most unsettling to Maurice. He had notes carped into biology only to find it personally as objection able as physics with its atomic consequences. The combination of both Linus and Francis breathing down his neck often made it very difficult to sleep. But at least Pauling was six thousand miles away, and even Francis was separated by a two-hour rail journey. The real problem, then, was Rosy. The thought could not be avoided that the best home for a feminist was in another person's.
3.
IT WAS Wilkins who had first excited me about X-ray work on DNA. This happened at Naples when a small scientific meeting was held on the structures of the large molecules found in living cells. Then it was the spring of 1951, before I knew of Francis Crick's existence. Already I was much involved with DNA, since I was in Europe on a postdoctoral fellowship to learn its biochemistry. My interest in DNA had grown out of a desire, first picked up while a senior in college, to learn what the gene was. Later, in graduate school at Indiana University, it was my hope that the gene might be solved without my learning any chemistry. This wish partially arose from laziness since, as an undergraduate at the University of Chicago, I was principally interested in birds and managed to avoid taking any chemistry or physics courses which looked of even medium difficulty. Briefly the Indiana biochemists encouraged me to learn organic chemistry, but after I used a bunsen burner to warm up some benzene, I was relieved from further true chemistry. It was safer to turn out an uneducated Ph.D. than to risk another explosion.
So I was not faced with the prospect of absorbing chemistry until I went to Copenhagen to do my postdoctoral research with the biochemist Herman Kalckar. Journeying abroad initially appeared the perfect solution to the complete lack of chemical facts in my head, a condition at times encouraged by my Ph.D. supervisor, the Italian trained microbiologist Salvador Luria. He positively abhorred most chemists, especially the competitive variety out of the jungles of New York City. Kalckar, however, was obviously cultivated, and Luria hoped that in his civilized, continental company I would learn the necessary tools to do chemical research, without needing to react against the profit-oriented organic chemists.
Then Luria's experiments largely dealt with the multiplication of bacterial viruses (bacteriophages, or phages for short). For some years the suspicion had existed among the more inspired geneticists that viruses were a form of naked genes. If so, the best way to find out what a gene was and how it duplicated was to study the properties of viruses. Thus, as the simplest viruses were the phages, there had sprung up between 1940 and 1950 a growing number of scientists (the phage group) who studied phages with the hope that they would eventually learn how the genes controlled cellular heredity. Leading this group were Luria and his German-born friend, the theoretical physicist Max Delbrück, then a professor at Cal Tech. While Delbrück kept hoping that purely genetic tricks could solve the problem, Luria more often wondered whether the real answer would come only after the chemical structure of a virus(gene) had been cracked open. Deep down he knew that it is impossible to describe the behavior of something when you don't know what it is. Thus, knowing he could never bring himself to learn chemistry, Luria felt the wisest course was to send me, his first serious student, to a chemist.
He had no difficulty deciding between a protein chemist and a nucleic acid chemist. Though only about one half the mass of a bacterial virus was DNA (the other half being protein), Avery's experiment made it smell like the essential genetic material. So working out DNA's chemical structure might be the essential step in learning how genes duplicated. Nonetheless, in contrast to the proteins, the solid chemical facts known about DNA were meager. Only a few chemists worked with it and, except for the fact that nucleic acids were very large molecule built up from smaller building blocks, the nucleotides, there was almost nothing chemical that the geneticist could grasp at. Moreover, the chemists who did work on DNA were almost always organic chemists with no interest in genetics. Kalckar was a bright exception. In the summer of 1945 he had come to the lab at Cold Spring, Harbor, New York, to take Delbrück's course on bacterial viruses. Thus both Luria and Delbrück hoped the Copenhagen lab would be the place where the combined techniques of chemistry and genetics might eventually yield real biological dividends.
Their plan, however, was a complete flop. Herman did not stimulate me in the slightest. I found myself just as indifferent to nucleic acid chemistry in his lab as I had been in the States. This was partly because I could not see how the type of problem on which he was then working (the metabolism of nucleotides) would lead to anything of immediate interest to genetics. There was also the fact that, though Herman was obviously civilized, it was impossible to understand him. I was able, however, to follow the English of Herman's close friend Ole Maaløe. Ole had just returned from the States (Cal Tech), where he had become very excited about the same phages on which I had worked for my degree. Upon his return he gave up his previous research problem and was devoting full time to phage. Then he was the only Dane working with phage and so was quite :pleased that I and Gunther Stent, a phage worker from Delbrück's lab, had come to do research with Herman. Soon Gunther and I found ourselves going regularly to visit Ole's lab, located several miles from Herman's, and within several weeks we were both actively doing experiments with Ole.
At first I occasionally felt ill at ease doing conventional phage work with Ole, since my fellowship was explicitly awarded to enable me to learn biochemistry with Herman; in a strictly literal sense I was violating its terms. Moreover, less than three months after my arrival in Copenhagen I was asked to propose plans for the following year. This was no simple matter, for I had no plans. The only safe course was to ask for funds to spend another year with Herman. It would have been risky to say that I could not make myself enjoy biochemistry. Furthermore, I could see no reason why they should not permit me to change my plans after the renewal was granted. I thus wrote to Washington saying that I wished to remain in the stimulating environment of Copenhagen. As expected, my fellowship was then renewed. It made sense to let Kalckar (whom several of the fellowship electors knew personally) train another biochemist.
There was also the question of Herman's feelings. Perhaps he minded the fact that I was only seldom around. True, he appeared very vague about most things and might not yet have really noticed. Fortunately, however, these fears never had time to develop seriously. Through a completely unanticipated event my moral conscience became clear. One day early in December, I cycled over to Herman's lab expecting another charming yet totally incomprehensible conversation. This time, however, I found Herman could be understood. He had something important to let out: his marriage was over, and he hoped to obtain a divorce. This fact was soon no secret everyone else in the lab was also told. Within a few days it became apparent that Herman's mind was not going to concentrate on science for some time, for perhaps as long as I would remain in Copenhagen. So the fact that he did not have to teach me nucleic-acid biochemistry was obviously a godsend. I could cycle each day over to Ole's lab, knowing it was clearly better to deceive the fellowship electors about where I was working than to force Herman.to talk about biochemistry.
At times, moreover, I was quite pleased with my current experiments on bacterial viruses. Within three months Ole and I had finished a set of experiments on the fate of a bacterial-virus particle when it multiplies inside a bacterium to form several hundred new virus particles. There were enough data for a respectable publication and, using ordinary standards, I knew I could stop work for the rest of the year without being judged unproductive. On the other hand, it was equally obvious that I had not done anything which was going to tell us what a gene was or how it reproduced. And unless I became a chemist, I could not see how I would.
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.
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| Anu - garden trees |
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. H I 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 ta1k on nucleic acids to be given by Randall. At that time almost nothing was published about the possible three-dimensional configurations of a nucleic acid 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?
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. H I 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 ta1k on nucleic acids to be given by Randall. At that time almost nothing was published about the possible three-dimensional configurations of a nucleic acid 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 ta1k 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 Xray 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 ta1k I had worried about the possibility that the gene might be fantastically irregu1ar. 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 a1ready 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 Paestu, did I get an opportunity to introduce myse1f. 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 comer 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 day: dreams 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.
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 Xray 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 ta1k I had worried about the possibility that the gene might be fantastically irregu1ar. 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 a1ready 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 Paestu, did I get an opportunity to introduce myse1f. 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 comer 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 day: dreams 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.
 |
| Lucas Cranach the Elder, Adam and Eve |
5.
I PROCEEDED to forget Maurice, but not this 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 cou1d not tell me whether 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 a 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.
By the time I was back to 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, Jobn 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 i insights; he seemed bored speaking about it. Even my in I.formation 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.
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 cou1d not tell me whether 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 a 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.
By the time I was back to 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, Jobn 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 i insights; he seemed bored speaking about it. Even my in I.formation 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.
 |
| Adam and Eve”, painting from the late III century (Cemetery of the Saints Peter and Marcellinus, Rome) |
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 he1ix. 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.
W e 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 f 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 r 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.
Naturally I was not at all prepared to receive a letter refusing permission. Ten days after my return to Cambridge, Herman forwarded the depressing news, which had been sent to my Copenhagen address. The Fellowship Board would not approve my transfer to a lab from which I was totally unprepared to profit. I was told to reconsider my plans, since I was unqualified to do crystallographic work. The Fellowship Board would, however, look favorably on a proposal that I transfer to the cellphysiology laboratory of Caspersson in Stockholm.
The source of the trouble was all too apparent. The head of the Fellowship Board no longer was Hans Clarke, a kindly biochemist friend of Herman's, then about to retire from Columbia. My letter had gone in~ stead to a new chairman, who took a more active interest in directing young people. He was put out that I had overstepped myself in denying that I would profit from biochemistry. I wrote to Luria to save me. He and the new man were casual acquaintances, and so when my decision was set in proper perspective, he might reverse his decision.
At first there were hints that Luria's interjection might cause a change back to reason. I was cheered up when a letter arrived from Luria that the situation might be, smoothed over if we appeared to eat crow. I was to write Washington that a major inducement in my wanting to be in Cambridge was the presence of Roy Markham, an English biochemist who worked with plant viruses. Markham took the news quite casually when I walked into his office and told him that he might acquire a model student who would never bother him by cluttering up his lab with experimental apparatus. He regarded the scheme as a perfect example of the inability of Americans to know how to behave. Nonetheless, he promised to go along with this nonsense.
Armed with the assurance that Markham would not squeal, I humbly wrote a long letter to Washington, outlining how I might profit from being in the joint presence of Perutz and Markham. At the end of the letter I thought it honest to break the news officially that I was in Cambridge and would remain there until a decision was made. The new man in Washington, however, did not play ball. The clue came when the return letter was addressed to Herman's lab. The Fellowship Board was considering my case. I would be informed when a decision had been made. Thus it did not seem prudent to cash my checks, which were still sent to Copenhagen at the beginning of each month.
Fortunately, the possibility of my not being paid in the forthcoming year for working on DNA was only annoying and not fatal. The $3000 fellowship stipend that I had received for being in Copenhagen was three times that required to live like a well-off Danish student. Even if I had to cover my sister's recent purchase of two fashionable Paris suits, I would have $1000 left, enough for a year's stay in Cambridge. My landlady was also helpful. She threw me out after less than a month's residence. My main crime was not removing my shoes when I entered the house after 9:00 P.M., the hour at which her husband went to sleep. Also I occasionally forgot the injunction not to flush the toilet at similar hours and, even worse, I went out after 10:00 P.M. Nothing in Cambridge was then open, and my motives were suspect. John and Elizabeth Kendrew rescued me with the offer, at almost no rent, of a tiny room in their house on Tennis Court Road. It was unbelievably damp and heated only by an aged electric heater. Nonetheless, I eagerly accepted the offer. Though it looked like an open invitation to tuberculosis, living with friends was infinitely preferable to any other digs I might find at this late moment so without any reluctance I decided to stay at Tennis Court Road until my financial picture improved.
7.
FROM my first day in the lab I knew I would not leave Cambridge for a long time, Departing would be idiocy, for I had immediately discovered the fun of talking to Francis Crick. Finding someone in Max's lab who knew that DNA was more important than proteins was real luck. Moreover, it was a great relief for me not to spend full time learning X ray analysis of proteins. Our lunch conversations quickly centered on how genes were put together. Within a few days after my arrival, we knew what to do: imitate Linus Pauling and beat him at his own game.
Pauling's success with the polypeptide chain had naturally suggested to Francis that the same tricks might also work for DNA. But as long as no one nearby thought DNA was at the heart of everything, the potential personal difficulties with the King's lab kept him from moving into action with DNA. Moreover, even though hemoglobin was not the center of the universe, Francis' previous two years at the Cavendish certainly had not been dull. More than enough protein problems kept popping up that required someone with a bent toward theory. But now, with me around the lab always wanting to talk about genes, Francis no longer kept his thoughts about DNA in a back recess of his brain. Even so, he had no intention of abandoning his interest in the other laboratory problems. No one should mind if, by spending only a few hours a week thinking about DNA, he helped me solve a smashingly important problem.
As a consequence, John Kendrew soon realized that I was unlikely to help him solve the myoglobin structure. Since he was unable to grow large crystals of horse myoglobin, he initially hoped I might have a greener thumb. No effort, however, was required to see that my laboratory manipulations were less skillful than those of a Swiss chemist. About a fortnight after my arrival in Cambridge, 37 we went out to the local slaughterhouse to get a horse heart for a new myoglobin preparation. If we were lucky, the damage to the myoglobin molecules which prevented crystallization would be averted by immediately freezing the ex racehorse's heart. But my subsequent attempts at crystallization were no more successful than John's. In a sense I was almost relieved. If they had succeeded, John might have put me onto taking X ray photographs.
No obstacle thus prevented me from talking at least several hours each day to Francis. Thinking all the time was too much even for Francis, and often when he was stumped by his equations he used to pump my reservoir of phage lore. At other moments Francis would endeavor to fill my brain With cyrstallographic facts, ordinarily available only through the painful reading of professional journals. Particularly important were the exact arguments needed to understand how Linus Pauling had discovered the α-helix.
I soon was taught that Pauling's accomplishment was a product of common sense, not the result of complicated mathematical reasoning. Equations occasionally crept into r his argument, but in most cases words would have sufficed. The key to Linus' success was his reliance on the simple Laws of structural chemistry. The α-helix had not been found by only staring at X ray pictures; the essential trick, instead, was to ask which atoms like to sit next to each other. In place of pencil and paper, the main working tools were a set of molecular models superficially resembling the toys of preschool children.
We could thus see no reason why we should not solve DNA in the same way. All we had to do was to construct a set of molecular models and begin to play with luck, the structure would be a helix. Any other type of configuration would be much more complicated. Worrying about complications before ruling out the possibility that the answer was simple would have been damned foolishness. Pauling never got anywhere by seeking out messes.
From our first conversations we assumed that the DNA molecule contained a very large number of nucleotides linear~ linked together in a regular way~ Again our reasoning was partially based upon simplicity. Although organic chemists in Alexander Todd's nearby lab thought this the basic arrangement, they were still a long way from chemically establishing that all the internucleotide bonds were identical. If this was not the case, however, we could not see how the DNA molecules packed together to form the crystalline aggregates studied by Maurice Wilkins and Rosalind Franklin. Thus, unless we found all future progress blocked, the best course was to regard the sugar phosphate backbone as extremely regular and to search for a helical three-dimensional configuration in which all the backbone groups had identical chemical environments.
Immediately we could see that the solution to DNA might be more tricky than that of the α-helix. In the α-helix, a single polypeptide ( a collection of amino acids) chain folds up into a helical arrangement held together by hydrogen bonds between groups on the same chain. Maurice had told Francis, however, that the diameter of the DNA molecule was thicker than would be the case of only one polynucleotide ( a collection of nucleotides ) chain were present. This made him think that the DNA molecule was a compound helix composed of several polynucleotide chains twisted about each other. If true, then before serious model building began, a decision would have to be made whether the chains would be held together by hydrogen bonds or by salt linkages involving the negatively charged phosphate groups.
A further complication arose from the fact that four types of nucleotides were found in DNA. In this sense, DNA was not a regular molecule but a highly irregular one. The four nucleotides were not, however, completely different, for each contained the same sugar and phosphate components. Their uniqueness lay in their nitrogenous bases, which were either a purine (adenine and guanine) or a pyrimidine (cytosine and thymine). But since the linkages between the nucleotides involved only the phosphate and sugar groups, our assumption that the same type of chemical bond linked all the nucleotides together was not affected. So in building models we would postu1ate that the sugar phosphate backbone was very regular, and the order of bases of necessity very irregular. If he base sequences were always the same, all DNA molecules would be identical and there would not exist the variability that must distinguish one gene from another. (Fig. 1)
 |
| Fig. 1. A short section of DNA as envisioned by Alexander Todd’s research group in 1951. They thought that all the internucleotide links were phosphodiester bonds joining sugar, carbon atom #5 to sugar carbon atom #5 of the adjacent nucleotide. As organic chemists they were concerned with how the atoms were linked together, leaving to crystallographers the problem of the 3-D arrangement of the atoms. |
Though Pauling had got the α-helix almost without the X ray evidence, he knew of its existence and to a certain extent had taken it into account. Given the X ray data, a large variety of possible three-dimensional configurations for the polypeptide chain were quickly discarded. The exact X ray data should help us go ahead much faster with the more subtly constructed DNA molecule. Mere inspection of the DNA X-ray picture should prevent a number of false starts. Fortunately, there already existed one ha1f good photograph in the published literature. It was taken five years previously by the English crystallographer W.T. Astbury, and could be used to start us off. Y et possession of Maurice's much better crystalline photograph's might save us from six months' to a year's work. The painful fact that the pictures belonged to Maurice could not be avoided.
There was nothing else to do but talk to him. To our surprise, Francis had no problem in persuading Maurice to come up to Cambridge for a weekend. And there was no need to force Maurice to the conclusion that the structure was a helix. Not only was it the obvious guess, but Maurice already had been talking in terms of helices at a summer meeting in Cambridge. About six weeks before I first arrived there, he had shown X ray diffraction pictures of DNA which revealed a marked absence of reflections on the meridian. This was a feature that his colleague, the theoretician Alex Stokes, had told him was compatible with α-helix. Given this conclusion, Maurice suspected that three polynucleotide chains were used to construct the helix.
There was nothing else to do but talk to him. To our surprise, Francis had no problem in persuading Maurice to come up to Cambridge for a weekend. And there was no need to force Maurice to the conclusion that the structure was a helix. Not only was it the obvious guess, but Maurice already had been talking in terms of helices at a summer meeting in Cambridge. About six weeks before I first arrived there, he had shown X ray diffraction pictures of DNA which revealed a marked absence of reflections on the meridian. This was a feature that his colleague, the theoretician Alex Stokes, had told him was compatible with α-helix. Given this conclusion, Maurice suspected that three polynucleotide chains were used to construct the helix.
He did not, however, share our belief that Pauling's model building game would quickly solve the structure, at least not until further X ray results were obtained. Most of our conversation, instead, centered on Rosy Franklin. More trouble than ever was coming from her. She was now insisting that not even Maurice himself should take any more X-ray photographs of DNA. In trying to come to terms with Rosy, Maurice made a very bad bargain. He had handed over to her all the good crystalline DNA used in his original work and had agreed to confine his studies to other DNA, which he afterward found did not crystallize. (Fig. 2)
 |
| Fig. 2. The chemical structures of the four DNA bases as they were often drawn about 1951. Because the electrons in the five- and six-membered rings are not localized, each base has a planar shape with a thickness of 3.4 Å. |
The point had been reached where Rosy would not even tell Maurice her latest results. The soonest Maurice was likely to learn where things stood was three weeks hence, the middle of November. At that time Rosy was scheduled to give a seminar on her past six months' work. Naturally I was delighted when Maurice said I would be welcome at Rosy's ta1k. For the first time I had a real incentive to learn some crystallography: I did not want Rosy to speak over my head.
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| Lilith with the apple and the serpent by Gail Potocki |
8.
MOST unexpectedly, Francis' interest in DNA temporarily fell to almost zero less than a week later. The cause was his decision to accuse a colleague of ignoring his ideas. The accusation was leveled at none other than his Professor. It happened less than a month after my arrival, on a Saturday morning. The previous day Max Perutz had given Francis a new manuscript by Sir Lawrence and himself, dealing with the shape of the hemoglobin molecule. As he rapidly read its contents Francis became furious, for he noticed that part of the argument depended upon a theoretical idea he had propounded some nine months earlier. What was worse, Francis remembered, having enthusiastically proclaimed it to everyone in the lab. Yet his contribution had not been acknowledged. A1most at once, after dashing in to tell Max and John Kendrew about the outrage, he hurried to Bragg's office for an explanation, if not an apology. But by then Bragg was at home, and Francis had to wait until the following morning. Unfortunately, this delay did not make the confrontation any more successful.
Sir Lawrence flatly denied prior knowledge of Francis' efforts and was thoroughly insulted by the implication that he had underhandedly used another scientist's ideas. On the other hand, Francis found it impossible to believe that Bragg could have been so dense as to have missed his oft-repeated idea, and he as much as told Bragg this. Further conversation became impossible, and in less than ten minutes Francis was out of the Professor's office.
For Bragg this meeting seemed the final straw in his relations with Crick. Several weeks earlier Bragg had come into the lab greatly excited about an idea that came to him the previous evening, one that he and Perutz subsequently incorporated in their paper. While he was explaining it to Perutz and Kendrew, Crick happened to join the group. To his considerable annoyance, Francis did not accept the idea immediately but instead stated that he would go away and check whether Bragg was right or wrong. At this stage Bragg had blown his top and, with his blood pressure all too high, returned home presumably to tell his wife about the latest antics of their problem child.
This most recent tussle was a disaster for Francis, and he showed his uneasiness when he came down to the lab. Bragg, in dismissing him from his room, had angrily told him that he would consider seriously whether he could continue to give Fra1icis a place in the laboratory after his Ph.D. course was ended. Francis was obviously worried that he might soon have to find a new position. Our sub-sequent lunch at the Eagle, the pub at which he usually ate, was restrained and unpunctuated by the usual laughter.
His concern was not without reason. Although he knew he was bright and could produce novel ideas, he could claim no clear-cut intellectual achievements and he was still without his Ph.D. He came from a solid middle-class family and was sent to school at Mill Hill. Then he read physics at University College, London, and had commenced work on an advanced degree when the war broke out. Like-almost all other English scientists, he joined the war effort and became part of the Admiralty's scientific establishment. There he worked with great vigor, and, al-though many resented his nonstop conversation, there was a war to win and he was quite helpful in producing ingenious magnetic mines. When the war was over, however, some of his colleagues saw no sound reason to have him about forever, and for a period he was given to believe that he had no future in the scientific civil service.
Moreover, he had lost all desire to stay in physics and decided instead to try biology. With the help of the physiologist A. V. Hill, he obtained a small grant to come up to Cambridge in the fall of 1947.At first he did true biology at the Strangeways Laboratory, but this was obviously trivial and two years later he moved over to the, Cavendish, where he joined Perutz and Kendrew. Here he again became excited about science and decided that per-haps he should finally work for a Ph.D. He thus enrolled as a research student ( of Caius College ) with Max as his supervisor. In a sense, this pursuit of the Ph.D. was a bore to a mind that worked too fast to be satisfied with the tedium involved in thesis research. On the other hand, his decision had yielded an unforeseen dividend in this moment of crisis, he could hardly be dismissed before he got his degree.
Max and John quickly came to Francis' rescue and interceded with the Professor. John confirmed that Francis, had previously written an account of the argument in question, and Bragg acknowledged that the same idea had occurred independently to both. Bragg by that time had calmed down, and any question of Crick's going was quietly shelved. Keeping him on was not easy on Bragg. One day in a moment of despair, he revealed that Crick, made his ears buzz. Moreover, he remained unconvinced that Crick was needed. Already for thirty-five years he had not stopped talking and almost nothing of fundamental value had emerged.
Sir Lawrence flatly denied prior knowledge of Francis' efforts and was thoroughly insulted by the implication that he had underhandedly used another scientist's ideas. On the other hand, Francis found it impossible to believe that Bragg could have been so dense as to have missed his oft-repeated idea, and he as much as told Bragg this. Further conversation became impossible, and in less than ten minutes Francis was out of the Professor's office.
For Bragg this meeting seemed the final straw in his relations with Crick. Several weeks earlier Bragg had come into the lab greatly excited about an idea that came to him the previous evening, one that he and Perutz subsequently incorporated in their paper. While he was explaining it to Perutz and Kendrew, Crick happened to join the group. To his considerable annoyance, Francis did not accept the idea immediately but instead stated that he would go away and check whether Bragg was right or wrong. At this stage Bragg had blown his top and, with his blood pressure all too high, returned home presumably to tell his wife about the latest antics of their problem child.
This most recent tussle was a disaster for Francis, and he showed his uneasiness when he came down to the lab. Bragg, in dismissing him from his room, had angrily told him that he would consider seriously whether he could continue to give Fra1icis a place in the laboratory after his Ph.D. course was ended. Francis was obviously worried that he might soon have to find a new position. Our sub-sequent lunch at the Eagle, the pub at which he usually ate, was restrained and unpunctuated by the usual laughter.
His concern was not without reason. Although he knew he was bright and could produce novel ideas, he could claim no clear-cut intellectual achievements and he was still without his Ph.D. He came from a solid middle-class family and was sent to school at Mill Hill. Then he read physics at University College, London, and had commenced work on an advanced degree when the war broke out. Like-almost all other English scientists, he joined the war effort and became part of the Admiralty's scientific establishment. There he worked with great vigor, and, al-though many resented his nonstop conversation, there was a war to win and he was quite helpful in producing ingenious magnetic mines. When the war was over, however, some of his colleagues saw no sound reason to have him about forever, and for a period he was given to believe that he had no future in the scientific civil service.
Moreover, he had lost all desire to stay in physics and decided instead to try biology. With the help of the physiologist A. V. Hill, he obtained a small grant to come up to Cambridge in the fall of 1947.At first he did true biology at the Strangeways Laboratory, but this was obviously trivial and two years later he moved over to the, Cavendish, where he joined Perutz and Kendrew. Here he again became excited about science and decided that per-haps he should finally work for a Ph.D. He thus enrolled as a research student ( of Caius College ) with Max as his supervisor. In a sense, this pursuit of the Ph.D. was a bore to a mind that worked too fast to be satisfied with the tedium involved in thesis research. On the other hand, his decision had yielded an unforeseen dividend in this moment of crisis, he could hardly be dismissed before he got his degree.
Max and John quickly came to Francis' rescue and interceded with the Professor. John confirmed that Francis, had previously written an account of the argument in question, and Bragg acknowledged that the same idea had occurred independently to both. Bragg by that time had calmed down, and any question of Crick's going was quietly shelved. Keeping him on was not easy on Bragg. One day in a moment of despair, he revealed that Crick, made his ears buzz. Moreover, he remained unconvinced that Crick was needed. Already for thirty-five years he had not stopped talking and almost nothing of fundamental value had emerged.
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| From right: art by Albrecht Dürer |
9.
A NEW opportunity to theorize soon brought Francis back to normal form. Several days after the fiasco with Bragg, the crystallographer V.Vand sent Max a letter containing a theory for the diffraction of X rays by helical molecules. Helices were then at the center of the lab's interest, largely because of Pauling's α-helix. Yet there was still lacking a general theory to test new models as well as to confirm the finer details of the α-helix. This is what Vand hoped his theory would do.
Francis quickly found a serious flaw in Vand's efforts, became excited about finding the right theory, and bounded upstairs to talk with Bill Cochran, a small, quiet Scot, then a lecturer in crystallography at the Cavendish. Bill was the cleverest of the younger Cambridge X-ray people, and even though he was not involved in work on the large biological macromolecules, he always provided the most astute sounding board for Francis' frequent ventures into theory. When Bill told Francis that an idea was unsound or would lead nowhere, Francis could be sure that professional jealousy was not involved. This time, however, Bill did not voice skepticism, since independently he had found faults in Vand's paper and had begun to wonder what the right answer was. For months both Max and Bragg had been after him to work out the helical theory, but he had not moved into action. Now, with the additional pressure from Francis, he too began seriously to ponder how the equations should be set up.
The remainder of the morning Francis was silent and absorbed in mathematical equations. At lunch at the Eagle a bad headache came on, and he went home instead of returning to the lab. But sitting in front of the gas fire doing nothing bored him, and again he took up his equations. To his delight, he soon saw that he had the answer. Nonetheless, he stopped his work, for he and his wife, Odile, were invited to a wine tasting at Matthews', one of Cambridge's better wine merchants. For several days his morale had been buoyed by the request to sample the wines. It meant acceptance by a more fashionable and amusing part of Cambridge and allowed him to dismiss the fact that he was not appreciated by a variety of dull and pompous dons.
He and Odile were then living at the "Green Door," a tiny, inexpensive flat on top of a several-hundred-year-old house just across Bridge Street from St. John's College. There were only two rooms of any size, a living room and a bedroom. All the others, including the kitchen, in which the bathtub was the largest and most conspicuous object, were almost nonexistent. But despite the cramp, its great charm, magnified by Odile's decorative sense, gave it a cheerful, if not playful, spirit. Here I first sensed the vitality of English intellectual life, so completely absent during my initial days in my Victorian room several hundred yards away on Jesus Green.
They had then been married for three years. Francis' first marriage did not last long, and a son, Michael, was looked after by Francis' mother and aunt. He had lived alone for several years until Odile, some five years his junior, came to Cambridge and hastened his revolt against the stodginess of the middle classes, which delight in unwicked amusements like sailing and tennis, habits particularly unsuited to the conversational life. Neither was politics or religion of any concern. The latter was clearly an error of past generations, which Francis saw no reason to perpetuate. But I am less certain about their complete lack of enthusiasm for political issues. Perhaps it was the war, whose grimness they now wished to forget. In any case, The Times was not present at breakfast, and more attention was given to Vogue, the only magazine to which they subscribed and about which Francis could converse at length.
By then I was often going to the Green Door for dinner. Francis was always eager to continue our conversations, while I joyously seized every opportunity to escape from the miserab1e English food that periodically led me to worry about whether I might have an ulcer. Odile's French mother had imparted to her a thorough contempt for the unimaginative way in which most Englishmen eat and house themselves. Francis thus never had reason to envy those college fellows whose High Table food was undeniably better than their wives' drab mixtures of tasteless meat, boiled potatoes, colorless greens, and typical trifles. Instead, dinner was often gay, especially after the wine turned the conversation to the currently talked-about Cambridge popsies.
There was no restraint in Francis' enthusiasms about young women-that is, as long as they showed some vitality and were distinctive in any way that permitted gossip and amusement. When young, he saw little of women and was only now discovering the spark1e they added to life. Odile did not mind this predilection, seeing that it went along with, and probably helped, his emancipation from the dullness of his Northampton upbringing. They would talk at length about the somewhat artsy-craftsy world in which Odile moved and into which they were frequently invited. No choice event was kept out of our conversations, and he would show equal gusto in telling of his occasional mistakes. One occurred when there was a costume party and he went looking like G. B. Shaw in a full red beard. As soon as he entered he realized that it was a ghastly error, since not one of the young women enjoyed being tickled by the wet, scraggly hairs when he came within kissing distance.
But there were no young women at the wine tasting. To his and Odile's dismay, their companions were college dons contentedly talking about the burdensome administrative problems with which they were so sadly afflicted. They went home early and Francis, unexpectedly sober, thought more about his answer.
The next morning he arrived in the lab and told Max and John about his success. A few minutes later, Bill Cochran walked into his office, and Francis started to re-peat the story. But before he could let loose his argument, Bill told him that he also thought he had succeeded. Hurriedly they went through their respective mathematics and discovered that Bill had used an elegant derivation compared to Francis' more laborious approach. Gleefully, however, they found that they had arrived at the same final answer. They then checked the α-helix by visual inspection with Max's X-ray diagrams. The agreement was so good that both Linus' model and their theory had to be correct.
Within a few days a polished manuscript was ready and jubilantly dispatched to Nature. At the same time, a copy was sent to Pauling to appreciate. This event, his first unquestionable success, was a signal triumph for Francis. For once the absence of women had gone along with luck.
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| Tree of life and death |
10.
BY mid-November, when Rosy's talk on DNA rolled about, I had learned enough crystallographic argument to follow much of her lecture.. Most important, I knew what to focus attention upon. Six weeks of listening to Francis had made me realize that the crux of the matter was whether Rosy's new X-ray pictures would lend any sup-port for a helical DNA structure. The really relevant experimental details were those which might provide clues in constructing molecular models. It took, however, only a few minutes of listening to Rosy to realize that her determined mind had set upon a different course of action.
She spoke to an audience of about fifteen in a quick, nervous style that suited the unornamented old lecture hall in which we were seated. There was not a trace of warmth or frivolity in her words. And yet I could not regard her as totally uninteresting. Momentarily I wondered how she would look if she took off her glasses and did something novel with her hair. Then, however, my main concern was her description of the crystalline X-ray dif-fraction pattern.
The years of careful, unemotional crystallographic training had left their mark. She had not had the advantage of a rigid Cambridge education only to be so foolish as to misuse it. It was downright obvious to her that the only way to establish the DNA structure was by pure crystallographic approaches. As model building did not appeal to her, at no time did she mention Pauling's triumph over the α-helix. The idea of using tinker-toy-like models to solve biological structures was clearly a last resort. Of course Rosy knew of Linus' success but saw no obvious reason to ape his mannerisms. The measure of his past triumphs was sufficient reason in itself to act differently; only a genius of his stature could play like a ten-year-old boy and still get the right answer.
Rosy regarded her talk as a preliminary report which, by itself, would not test anything fundamental about DNA. Hard facts would come only when further data had been collected which could allow the crystallographic analyses to be carried to a more refined stage. Her lack of immediate optimism was shared by the small group of lab people who came to the talk. No one else brought up the desirability of using molecular models to help solve the structure. Maurice himself only asked several questions of a technical nature. The discussion then quickly stopped with the expressions on the listeners' faces indicating either that they had nothing to add or that, if they did wish to say something, it would be bad form since they had said it before. Maybe their reluctance to utter anything romantically optimistic, or even to mention models, was due to fear of a sharp retort from Rosy. Certainly a bad way to go out into the foulness of a heavy, foggy November night was to be told by a woman to refrain from, venturing an opinion about a subject for which you were not trained. It was a sure way of bringing back unpleasant memories of lower school.
Following some brief and, as I was later to observe, characteristically tense small talk with Rosy, Maurice and I walked down the Strand and across to Choy's Restaurant in Soho. Maurice's mood was surprisingly jovial. Slowly and precisely he detailed how, in spite of much elaborate crystallographic analysis, little real progress had been made by Rosy since the day she arrived at King's. Though her X-ray photographs were somewhat sharper than his, she was unable to say anything more positive than he had already. True, she had done some more de-tailed measurements of the water content of her DNA samples, but even here Maurice had doubts about whether she was really measuring what she claimed.
To my surprise, Maurice seemed buoyed up by my presence. The aloofness that existed when we first met in Naples had vanished. The fact that 1, a phage person, found what he was doing important was reassuring. It really was no help to receive encouragement from a fellow physicist. Even when he met those who thought his decision to go into biology made sense, he couldn't trust their judgment. After all, they didn't know any biology, and so it was best to take their remarks as politeness, even condescension, toward someone opposed to the competitive pace of postwar physics.
To be sure, he got active and very necessary help from some biochemists. If not, he could never have come into the game. Several of them had been absolutely vital in generously providing him with samples of highly purified DNA. It was bad enough learning crystallography without having to acquire the witchcraft-like techniques of the biochemist. On the other hand, the majority weren't like the high-powered types he had worked with on the bomb project. Sometimes they seemed even ignorant of the way DNA was important.
But even so they knew more than the majority of biologists. In England, if not everywhere, most botanists and zoologists were a muddled lot. Not even the possession of University Chairs gave many the assurance to do clean science; some actually wasted their efforts on useless polemics about the origin of life or how we know that a scientific fact is really correct. What was worse, it was possible to get a university degree in biology without learning any genetics. That was not to say that the geneticists themselves provided any intellectual help. You would have thought that with all their talk about genes they should worry about what they were. Yet almost none of them seemed to take seriously the evidence that genes were made of DNA. This fact was unnecessarily chemical. All that most of them wanted out of life was to set their students onto uninterpretable details of chromosome behavior or to give elegantly phrased, fuzzy-minded speculations over the wireless on topics like the role of the geneticist in this transitional age of changing values.
So the knowledge that the phage group took DNA seriously made Maurice hope that times would change and he would not have painfully to explain, each time he gave a seminar, why his lab was making so much fuss and bother about DNA. By the time our dinner was finished, he was clearly in a mood to push ahead. Yet all too suddenly Rosy popped back into the conversation, and the possibility of really mobilizing his lab's efforts slowly I receded as we paid the bill and went out into the night.
To be sure, he got active and very necessary help from some biochemists. If not, he could never have come into the game. Several of them had been absolutely vital in generously providing him with samples of highly purified DNA. It was bad enough learning crystallography without having to acquire the witchcraft-like techniques of the biochemist. On the other hand, the majority weren't like the high-powered types he had worked with on the bomb project. Sometimes they seemed even ignorant of the way DNA was important.
But even so they knew more than the majority of biologists. In England, if not everywhere, most botanists and zoologists were a muddled lot. Not even the possession of University Chairs gave many the assurance to do clean science; some actually wasted their efforts on useless polemics about the origin of life or how we know that a scientific fact is really correct. What was worse, it was possible to get a university degree in biology without learning any genetics. That was not to say that the geneticists themselves provided any intellectual help. You would have thought that with all their talk about genes they should worry about what they were. Yet almost none of them seemed to take seriously the evidence that genes were made of DNA. This fact was unnecessarily chemical. All that most of them wanted out of life was to set their students onto uninterpretable details of chromosome behavior or to give elegantly phrased, fuzzy-minded speculations over the wireless on topics like the role of the geneticist in this transitional age of changing values.
So the knowledge that the phage group took DNA seriously made Maurice hope that times would change and he would not have painfully to explain, each time he gave a seminar, why his lab was making so much fuss and bother about DNA. By the time our dinner was finished, he was clearly in a mood to push ahead. Yet all too suddenly Rosy popped back into the conversation, and the possibility of really mobilizing his lab's efforts slowly I receded as we paid the bill and went out into the night.
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| Ancient Aryan Tree of Life |
11.
THE following morning I joined Francis at Paddington Station. From there we were to go up to Oxford to spend the weekend. Francis wanted to talk to Dorothy Hodgkin, the best of the English crystallographers, while I welcomed the opportunity to see Oxford for the first time. At the train gate Francis was in top form. The visit would give him the opportunity to tell Dorothy about his success with Bill Cochran in working out the helical diffraction theory. The theory was much too elegant not to be told in person individuals like Dorothy who were clever enough to understand its power immediately were much too rare.
As soon as we were in the train carriage, Francis began asking questions about Rosy's talk. My answers were frequently vague, and Francis was visibly annoyed by my habit of always trusting to memory and never writing anything on paper. If a subject interested me, I could usually recollect what I needed. This time, however, we were in trouble, because I did not know enough of the crystallographic jargon. Particularly unfortunate was my failure to be able to report exactly the water content of the DNA samples upon which Rosy had done her measurements. The possibility existed that I might be misleading Francis by an order of magnitude difference.
The wrong person had been sent to hear Rosy. If Francis had gone along, no such ambiguity would have existed. It was the penalty for being oversensitive to the situation. For, admittedly, the sight of Francis mulling over the consequences of Rosy's information when it was hardly out of her mouth would have upset Maurice. In one sense it would be grossly unfair for them to learn the facts at the same time. Certainly Maurice should have the first chance to come to grips with the problem. On the other hand, there seemed no indication that he thought the answer would come from playing with molecular models. our conversation on the previous i1ight had hardly alluded to that approach. Of course, the possibility existed that he was keeping something back. But that was very unlikely Maurice just wasn't that type.
The only thing that Francis could do immediately was to seize the water value, which was the easiest to think, about. Soon something appeared to make sense, and he began scribbling on the vacant back sheet of a manuscript, he had been reading. By then I could not understand what Francis was up to and reverted to The Times for amusement. Within a few minutes, however, Francis made me lose all interest in the outside world by telling me that only a small number of formal solutions were compatible both with the Cochran Crick theory and with Rosy's experimental data. Quickly he began to draw more diagrams to show me how simple the problem was. Though the mathematics eluded me, the crux of the matter was not difficult to follow. Decisions had to be made about the number of polynucleotide chains within the DNA molecule. Superficially, the Xray data were compatible with two, three, or four strands. It was all a question of the angle and radii at which the DNA strands twisted about the central axis.
By the time the hour and a half train journey was over, Francis saw no reason why we should not know the answer soon. Perhaps a week of solid fiddling wi1h the molecular models would be necessary to make us absolutely sure we had the right answer. Then it would be obvious to the world that Pauling was not the only one capable of true insight into how biological molecules were, constructed. Linus' capture of the α-helix was most embarrassing for the Cambridge group. About a year before that triumph, Bragg, Kendrew, and Perutz had published a systematic paper on the conformation of the polypeptide chain, an attack that missed the point. Bragg in fact was still bothered by the fiasco. It hurt his pride at a tender point. There had been previous encounters with Pauling, stretching over a twenty-five-year interval. All too often Linus had got there first.
Even Francis was somewhat humiliated by the event. He was already' in the Cavendish when Bragg had become keen about how a polypeptide chain folded up. Moreover, he was privy to a discussion in which the fundamental blunder about the shape of the peptide bond was made. That had certainly been the occasion to interject his critical facility in assessing the meaning of experimental observations but he had said nothing useful. It was not that Francis normally refrained from criticizing his friends. In other instances he had been annoyingly candid in pointing out where Perutz and Bragg had publicly over interpreted their hemoglobin results. This open criticism was certainly behind Sir Lawrence's recent outburst against him. In Bragg's view, all that Crick did was, to rock the boat.
Now, however, was not the time to concentrate on past mistakes. Instead, the speed with which we talked about possible types of DNA structures gathered intensity as the morning went by. No matter in whose company we found ourselves, Francis would quickly survey the progress of the past few hours, bringing our listener up to date on how we had decided upon models in which the sugar-phosphate backbone was in the center of the molecule. Only in that way would it be possible to obtain a structure regular enough to give the crystalline diffraction patterns observed by Maurice and Rosy. True, we had yet to deal with the irregular sequence of the bases that faced the outside but this difficulty right vanish in the wash when the correct internal arrangement was located.
There was also the problem of what neutralized the negative charges of the phosphate groups of the DNA backbone. Francis, as well as 1, knew almost nothing about how inorganic ions were arranged in three dimensions. We had to face the bleak situation that the world authority on the structural chemistry of ions was Linus Pauling himself. Thus if the crux of the problem was to deduce an unusually clever arrangement of inorganic ions and phosphate groups, we were clearly at a disadvantage. By midday it became imperative to locate a copy of Pauling's classic book, The Nature of the Chemical Bond. Then we were having lunch near High Street. Wasting no time over coffee, we dashed into several bookstores until success came in Blackwell's. A rapid reading was made of the relevant sections. This produced the correct values for the exact sizes of the candidate inorganic ions, but nothing that could help push the problem over the top.(Fig. 3)
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| Fig. 3. A more detailed view of the bivalent bonds of the sugar-phosphate backbone. |
When we reached Dorothy's lab in the University Museum, the manic phase had almost passed. Francis ran through the helical theory itself, devoting only a few minutes to our progress with DNA. Most of the conversation centered instead on Dorothy's recent work with insulin. Since darkness was coming on, there seemed no point in wasting more of her time. We then moved on to Magdalen, where we were to have tea with Avrion Mitchison and Leslie Orgel, both then fellows of the college. Over cakes Francis was ready to talk about trivial things, while I quietly thought how splendid it would be if I could some day live in the style of a Magdalen don.
Dinner with claret, however, restored the conversation to our impending triumph with DNA. By then we had been joined by Francis' close friend, the logician George Kreisel, whose unwashed appearance and idiom did not fit into my picture of the English philosopher. Francis greeted his arrival with great gusto, and the sound of Francis' laughter and Kreisel's Austrian accent dominated the spiffy 'atmosphere of the restaurant along High Street at which Kreisel had directed us to meet him. For a while Kreisel held forth on a way to make a financial killing by shifting money between the politically divided parts of Europe. Avrion Mitchison then rejoined us, and the conversation for a short time reverted to the casual banter of the intellectual middle class. This sort of small talk, however, was not Kreisel's meat, and so Avrion and I excused ourselves to walk along the medieval streets toward my lodgings. By then I was pleasantly drunk and spoke at length of what we could do when we had DNA.
Dinner with claret, however, restored the conversation to our impending triumph with DNA. By then we had been joined by Francis' close friend, the logician George Kreisel, whose unwashed appearance and idiom did not fit into my picture of the English philosopher. Francis greeted his arrival with great gusto, and the sound of Francis' laughter and Kreisel's Austrian accent dominated the spiffy 'atmosphere of the restaurant along High Street at which Kreisel had directed us to meet him. For a while Kreisel held forth on a way to make a financial killing by shifting money between the politically divided parts of Europe. Avrion Mitchison then rejoined us, and the conversation for a short time reverted to the casual banter of the intellectual middle class. This sort of small talk, however, was not Kreisel's meat, and so Avrion and I excused ourselves to walk along the medieval streets toward my lodgings. By then I was pleasantly drunk and spoke at length of what we could do when we had DNA.
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| Kolovrat and Tree of Life |
12.
I GAVE John and Elizabeth Kendrew the scoop about DNA when I joined them for breakfast on Monday morning. Elizabeth appeared delighted that success was almost within our grasp, while John took the news more calmly. When it came out that Francis was again in an inspired, mood and I had nothing more solid to report than enthusiasm, he became lost to the sections of The Times which spoke about the first days of the new Tory government. Soon afterward, John went off to his rooms in Peterhouse, leaving Elizabeth and me to digest the implications of my unanticipated luck. I did not remain long, since the sooner I could get back to the lab, the quicker we could find out which of the several possible answers would be favored by a hard look at the molecular models themselves.
Both Francis and 1, however, knew that the models in the Cavendish would not be completely satisfactory. They had been constructed by John some eighteen months before, for the work on the three-dimensional shape of the polypeptide chain. There existed no accurate representations of the groups of atoms unique to DNA. Neither phosphorus atoms nor the purine and pyrimidine bases were on hand. Rapid improvisation would be necessary since there was no time for Max to give a rush order for their construction. Making brand new models might take all of a week, whereas an answer was possible within a day or so. Thus as soon as I got to the lab I began adding bits of copper wire to some of our carbon atom models, thereby changing them into the larger sized phosphorus atoms. (Fig. 4)
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| Fig. 4. A schematic view of a nucleotide, showing that the plane of the base is almost perpendicular to the plane in which most of the sugar atoms lie. This important fact was established in 1949 by S. Furberg, then working in London at J. D. Bernal's Birkbeck College lab. Later he built some very tentative models for DNA, but not knowing the details of the King's College experiments, he built only single-stranded structures, and so his structural ideas were never seriously considered in the Cavendish. |
Much more difficulty came from the necessity to fabricate representations of the inorganic ions. Unlike the other constituents, they obeyed no simpleminded rules telling us the angles at which they would form their respective chemical bonds. Most likely we had to know the correct DNA structure before the right models could be made. I maintained the hope, however, that Francis might already be on to the vital trick and would immediately blurt it out when he got to the lab. Over eighteen hours had passed since our last conversation, and there was little chance that the Sunday papers would have distracted him upon his return to the Green Door.
His tenish entrance, however, did not bring the answer. After Sunday supper he had again run through the dilemma but saw no quick answer. The problem was then put aside for a rapid scanning of a novel on the sexual misjudgments of Cambridge dons. The book had its brief good moments, and even in its most ill-conceived pages there was the question of whether any of their friends' lives had been seriously drawn on in the construction of the plot.
Over morning coffee Francis nonetheless exuded confidence that enough experimental data might already be on hand to determine the outcome. We might be able to start the game with several completely different sets of facts and yet always hit the same final answers. Perhaps the whole problem would fall out just by our concentrating on the prettiest way for a polynucleotide chain to fold up. So while Francis continued thinking about the meaning of the X-ray diagram, I began to assemble the various atomic models into several chains, each several nucleotides in length. Though in nature DNA chains are very long, there was no reason to put together anything massive. As long as we could be sure it was a helix, the assignment of the positions for only a couple of nucleotides automatically generated the arrangement of all the other components.
The routine assembly task was over by one, when Francis and I walked over to the Eagle for our habitual lunch with the chemist Herbert Gutfreund. These days John usually went to Peterhouse, while Max always cycled home. Occasionally John's student Hugh Huxley would join us, but of late he was finding it difficult to enjoy Francis' inquisitive lunchtime attacks. For just prior to my arrival in Cambridge, Hugh's decision to take up the problem of how muscles contract had focused Francis' attention on the unforeseen opportunity that, for twenty years or so, muscle physiologists had been accumulating data without tying them into a se1fconsistentr picture. Francis found it a perfect situation for action. There was no need for him to ferret out the relevant experiments since Hugh had already waded through the undigested mass. Lunch after lunch, the facts were put together to form theories which held for a day or so, until Hugh could convince Francis that a result he would like ascribed to experimental error was as solid as the Rock of Gibraltar. Now the construction of Hugh's X-ray camera was completed, and soon he hoped to get experimental evidence to settle the debatable points. The fun would be all lost if somehow Francis could correctly predict what he was going to find. (Fig. 5)
His tenish entrance, however, did not bring the answer. After Sunday supper he had again run through the dilemma but saw no quick answer. The problem was then put aside for a rapid scanning of a novel on the sexual misjudgments of Cambridge dons. The book had its brief good moments, and even in its most ill-conceived pages there was the question of whether any of their friends' lives had been seriously drawn on in the construction of the plot.
Over morning coffee Francis nonetheless exuded confidence that enough experimental data might already be on hand to determine the outcome. We might be able to start the game with several completely different sets of facts and yet always hit the same final answers. Perhaps the whole problem would fall out just by our concentrating on the prettiest way for a polynucleotide chain to fold up. So while Francis continued thinking about the meaning of the X-ray diagram, I began to assemble the various atomic models into several chains, each several nucleotides in length. Though in nature DNA chains are very long, there was no reason to put together anything massive. As long as we could be sure it was a helix, the assignment of the positions for only a couple of nucleotides automatically generated the arrangement of all the other components.
The routine assembly task was over by one, when Francis and I walked over to the Eagle for our habitual lunch with the chemist Herbert Gutfreund. These days John usually went to Peterhouse, while Max always cycled home. Occasionally John's student Hugh Huxley would join us, but of late he was finding it difficult to enjoy Francis' inquisitive lunchtime attacks. For just prior to my arrival in Cambridge, Hugh's decision to take up the problem of how muscles contract had focused Francis' attention on the unforeseen opportunity that, for twenty years or so, muscle physiologists had been accumulating data without tying them into a se1fconsistentr picture. Francis found it a perfect situation for action. There was no need for him to ferret out the relevant experiments since Hugh had already waded through the undigested mass. Lunch after lunch, the facts were put together to form theories which held for a day or so, until Hugh could convince Francis that a result he would like ascribed to experimental error was as solid as the Rock of Gibraltar. Now the construction of Hugh's X-ray camera was completed, and soon he hoped to get experimental evidence to settle the debatable points. The fun would be all lost if somehow Francis could correctly predict what he was going to find. (Fig. 5)
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| Fig. 5. How Mg++ ions might be used to bind negatively charged phosphate groups in the center of a compound helix. |
But there was no need that day for Hugh to fear a new intellectual invasion. When we walked into the Eag1e, Francis did not exchange his usual raucous greetings with the Persian economist Ephraim Eshag, but gave the distilled impression that something serious was up. The actual model building would start right after lunch, and more concrete plans must be formulated to make the process efficient so over our gooseberry pie we looked at the pros and cons of one, two, three, and four chains, quickly dismissing one chain helices as incompatible with the evidence in our hands. As to the forces that held the chains together, the best guess seemed to be salt bridges in which divalent cations like Mg++ held together two or more phosphate groups. Admittedly there was no evidence that Rosy's samples contained any divalent ions, and so we might be sticking our necks out. On the other hand, there was absolutely no evidence against our hunch. If only the King's groups had thought about models, they would have asked which salt was present and we would not be placed in this tiresome position. But, with luck, the addition of magnesium or possibly calcium ions to the sugar-phosphate backbone would quickly generate an elegant structure, the correctness of which would not be debatable.
Our first minutes with the mode1s, though, were not joyous. Even though only about fifteen atoms were involved, they kept falling out of the awkward pincers setup to hold them the correct distance from one another. Even worse, the uncomfortable impression arose that there were no obvious restrictions on the bond angles between several of the most important atoms. This was not at all nice. Pauling had cracked the α-helix by ruthlessly following up his knowledge that the peptide bond was flat. To our annoyance, there seemed every reason to believe that the phosphodiester bonds which bound together the successive nucleotides in DNA might exist in a variety of shapes. At least with our level of chemical intuition, there was unlikely to be any single conformation much prettier than the rest.
After tea, however, a shape began to emerge which brought back our spirits. Three chains twisted about each other in a way that gave rise to a crystallographic repeat every 28 A along the helical axis. This was a feature demanded by Maurice's and Rosy's pictures, so Francis was visibly reassured as he stepped back from the lab bench and surveyed the afternoon's effort. Admittedly a few of the atomic contacts were still too close for comfort, but, after all, the fiddling had just begun. With a few hours' more work, a presentable model should be on display.
Our first minutes with the mode1s, though, were not joyous. Even though only about fifteen atoms were involved, they kept falling out of the awkward pincers setup to hold them the correct distance from one another. Even worse, the uncomfortable impression arose that there were no obvious restrictions on the bond angles between several of the most important atoms. This was not at all nice. Pauling had cracked the α-helix by ruthlessly following up his knowledge that the peptide bond was flat. To our annoyance, there seemed every reason to believe that the phosphodiester bonds which bound together the successive nucleotides in DNA might exist in a variety of shapes. At least with our level of chemical intuition, there was unlikely to be any single conformation much prettier than the rest.
After tea, however, a shape began to emerge which brought back our spirits. Three chains twisted about each other in a way that gave rise to a crystallographic repeat every 28 A along the helical axis. This was a feature demanded by Maurice's and Rosy's pictures, so Francis was visibly reassured as he stepped back from the lab bench and surveyed the afternoon's effort. Admittedly a few of the atomic contacts were still too close for comfort, but, after all, the fiddling had just begun. With a few hours' more work, a presentable model should be on display.
Ebullient spirits prevailed during the evening meal at the Green Door. Though Odile could not follow what we were saying, she was obviously cheered by the fact that Francis was about to bring off his second triumph within the month. If this course of events went on, they would soon be rich and could own a car. At no moment did Francis see any point in trying to simplify the matter for Odile's benefit. Ever since she had told him that gravity went only three miles into the sky, this aspect of their relationship was set. Not only did she not know any science, but any attempt to put some in her head would be a losing fight against the years of her convent upbringing. The most to hope for was an appreciation of the linear way in which money was measured.
Our conversation instead centered upon a young art student then about to Marry Odile's friend Harmut Weil. This capture was mildly displeasing to Francis. It was about to remove the prettiest girl from their party circle. Moreover, there was more than one thing cloudy about Harmut. He had come out of a German university tradition that believed in dueling. There was also his undeniable skill in persuading numerous Cambridge women to pose for his camera.
All thought of women, however, was banished by the time Francis breezed into the lab just before morning coffee. Soon, when several atoms had been pushed in or out, the three-chain model began to look quite reasonable. The next obvious step would be to check it with Rosy's quantitative measurements. The model would certainly fit with the general locations of the X-ray reflections, for its essential helical parameters had been chosen to fit the seminar facts I had conveyed to Francis. If it were right, however, the model would also accurately predict the relative intensities of the various X-ray reflections.
A quick phone call was made to Maurice. Francis explained how the helical diffraction theory allowed a rapid survey of possible DNA models, and that he and I had just come up with a creature which might be the answer we were all awaiting. The best thing would be for Maurice immediately to come and look it over. But Maurice gave no definite date, saying he thought he might make it sometime within the week. Soon after the phone was putdown, John came in to see how Maurice had taken the news of the breakthrough. Francis found it hard to sum up his reply. It was almost as if Maurice were indifferent to what we were doing.
In the midst of further fiddling that afternoon, a call came through from King's. Maurice would come up on the 10:10 train from London the following morning. Moreover, he would not be alone. His collaborator Willy Seeds would also come. Even more to the point was that Rosy, together with her student R. G. Gosling, would be on the same train. Apparently they were still interested in the answer.
Our conversation instead centered upon a young art student then about to Marry Odile's friend Harmut Weil. This capture was mildly displeasing to Francis. It was about to remove the prettiest girl from their party circle. Moreover, there was more than one thing cloudy about Harmut. He had come out of a German university tradition that believed in dueling. There was also his undeniable skill in persuading numerous Cambridge women to pose for his camera.
All thought of women, however, was banished by the time Francis breezed into the lab just before morning coffee. Soon, when several atoms had been pushed in or out, the three-chain model began to look quite reasonable. The next obvious step would be to check it with Rosy's quantitative measurements. The model would certainly fit with the general locations of the X-ray reflections, for its essential helical parameters had been chosen to fit the seminar facts I had conveyed to Francis. If it were right, however, the model would also accurately predict the relative intensities of the various X-ray reflections.
A quick phone call was made to Maurice. Francis explained how the helical diffraction theory allowed a rapid survey of possible DNA models, and that he and I had just come up with a creature which might be the answer we were all awaiting. The best thing would be for Maurice immediately to come and look it over. But Maurice gave no definite date, saying he thought he might make it sometime within the week. Soon after the phone was putdown, John came in to see how Maurice had taken the news of the breakthrough. Francis found it hard to sum up his reply. It was almost as if Maurice were indifferent to what we were doing.
In the midst of further fiddling that afternoon, a call came through from King's. Maurice would come up on the 10:10 train from London the following morning. Moreover, he would not be alone. His collaborator Willy Seeds would also come. Even more to the point was that Rosy, together with her student R. G. Gosling, would be on the same train. Apparently they were still interested in the answer.
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| Yggdrasil (nordic Tree of Life) |
13.
MAURICE decided to take a cab from the station to the lab. Ordinarily he would have come by bus, but now there were four of them to share the cost. Moreover, there would be no satisfaction in waiting at the bus stop with Rosy. It would make the present uncomfortable situation worse than it need be. His well intentioned remarks never came off, and even now, when the possibility of humiliation hung over them, Rosy was as indifferent as ever to his presence and directed all her attention to Gosling. There was only the slightest effort made at a united appearance when Maurice poked his head into our lab to say they had come. Especially in sticky situations like this, Maurice thought that a few minutes without science was the way to proceed. Rosy, however, had not come here to throw out foolish words, but quickly wanted to know where things stood.
Neither Max nor John did anything to take the stage away from Francis. This was his day, and after they came in to greet Maurice they both pleaded pressure of their work to retire behind the closed doors of their joint office. Before the delegation's arrival, Francis and I had agreed to reveal our progress in two stages. Francis would first sum up the advantages of the helical theory. Then together we could explain how we had arrived at the proposed model for DNA. Afterwards we could go to the Eagle for lunch, leaving the afternoon free to discuss how we could all proceed with the final phases of the problem.
The first part of the show ran on schedule. Francis saw no reason to understate the power of the helical theory and within several minutes revealed the way Bessel functions gave neat answers. None of the visitors, however, gave any indication of sharing Francis' delight. Instead of wishing to do something with the pretty equations, Maurice wanted to concentrate on the fact that the theory did not go beyond some mathematics his colleague. Stokes had worked out without all this fanfare. Stokes had solved the problem in the train while going home one evening and had produced the theory on a small sheet of paper the next morning.
Rosy did not give a hoot about the priority of the creation of the helical theory and, as Francis prattled on, she displayed increasing irritation. The sermon was unnecessary, since to her mind there was not a shred of evidence that DNA was helical. Whether this was the case would come out of further X-ray work. Inspection of the m04elitself only increased her disdain. Nothing in Francis’ argument justified all this fuss. She became positively aggressive when we got on the topic of Mg++ ions that held together the phosphate groups of our three-chain model. This feature had no appeal at all to Rosy, who curtly pointed out that the Mg++ ions would be surrounded by tight shells of water molecules and so were unlikely to be the kingpins of a tight structure.
Most annoyingly, her objections were not mere perversity: at this stage the embarrassing fact came out that my recollection of the water content of Rosy's DNA samples could not be right. The awkward truth became apparent that the correct DNA model must contain at least ten times more water than was found in our model. This did not mean that we were necessarily wrong ― with luck the extra water might be fudged into vacant regions on the periphery of our helix. On the other hand, there was no escaping the conclusion that our argument was soft. As soon as the possibility arose that much more water was, involved, the number of potential DNA models alarmingly increased.
Though Francis could not help dominating the lunchtime conversation, his mood was no longer that of a confident master lecturing hapless colonial children who until then had never experienced a first rate intellect. The group holding the ball was clear to all. The best way to salvage something from the day was to come to an agreement about the next round of experiments. In particular, only a few weeks' work should be necessary to see whether the DNA structure was dependent upon the exact ions used to neutralize the negative phosphate groups. Then the beastly uncertainty as to whether Mg++ ions were important could vanish. With this accomplished, another round of model building could start and, given luck, it might occur by christmas.
Our subsequent after-lunch walk into King's and along the backs to Trinity did not, however, reveal any converts. Rosy and Gosling were pugnaciously assertive: their future course of action would be unaffected by their fifty mile excursion into adolescent blather. Maurice and Willy Seeds gave more indication of being reasonable, but there was no certainty that this was anything more than a reflection of a desire not to agree with Rosy.
The situation did not improve when we got back to the lab. Francis did not want to surrender immediately, so he went through some of the actual details of how we went about the model building. Nonetheless, he quickly lost heart when it became apparent that I was the only one joining the conversation. Moreover, by this time neither of us really wanted to look at our model. All its glamour had vanished, and the crudely improvised phosphorus atoms gave no hint that they would ever neatly fit into something of value. Then when Maurice mentioned that, if they moved with haste, the bus might enable them to get the 3:40 train to Liverpool Street Station, we quickly said goodbye.
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| Celtic Tree of Life |
14.
Rosy's triumph all too soon filtered up the stairs to Bragg. There was nothing to do but appear unperturbed as the news of the upset confirmed the fact that Francis might move faster if occasionally he would close his mouth. The consequences spread in a predictable fashion. Clearly this was the moment for Maurice's boss to discuss with Bragg whether it made sense for Crick and the American to duplicate King's heavy investment in DNA.
Sir Lawrence had had too much of Francis to be surprised that he had again stirred up an unnecessary tempest. There was no telling where he would let loose the next explosion. If he continued to behave this way, he could easily spend the next five years in the lab without collecting sufficient data to warrant an honest Ph.D. The chilling prospect of enduring Francis throughout the remaining years of his tenure as the Cavendish Professor was too much to ask of Bragg or anyone with a normal set of nerves. Besides, for too long he had lived under the shadow of his famous father, with most people falsely thinking that his father, not he, was responsible for the sharp insight behind Bragg's Law. Now when he should be enjoying the rewards accorded the most prestigious chair in science, he had to be responsible for the outrageous antics of an unsuccessful genius.
Sir Lawrence had had too much of Francis to be surprised that he had again stirred up an unnecessary tempest. There was no telling where he would let loose the next explosion. If he continued to behave this way, he could easily spend the next five years in the lab without collecting sufficient data to warrant an honest Ph.D. The chilling prospect of enduring Francis throughout the remaining years of his tenure as the Cavendish Professor was too much to ask of Bragg or anyone with a normal set of nerves. Besides, for too long he had lived under the shadow of his famous father, with most people falsely thinking that his father, not he, was responsible for the sharp insight behind Bragg's Law. Now when he should be enjoying the rewards accorded the most prestigious chair in science, he had to be responsible for the outrageous antics of an unsuccessful genius.
The decision was thus passed on to Max that Francis and I must give up DNA. Bragg felt no qualms that this might impede science, since inquiries to Max and John had revealed nothing original in our approach. After Pauling's success, no one could claim that faith in helices implied anything but an uncomplicated brain. Letting the King's group have the first go at helical models was the right thing in any circumstance. Crick could then buckle down to his thesis task of investigating the ways that hemoglobin crystals shrink when they are placed in salt solutions of different density. A year to eighteen months of steady work might tell something more solid about the shape of the hemoglobin molecule. With a Ph.D. in his pocket Crick could then seek employment elsewhere.
No attempt was made to appeal the verdict. To the relief of Max and John, we refrained from publicly questioning Bragg's decision. An open outcry would reveal that our professor was completely in the dark about what the initials DNA stood for. There was no reason to believe that he gave it one hundredth the importance of the structure of metals, for which he took great delight in making soap-bubble mode1s. Nothing then gave Sir Lawrence more pleasure than showing his ingenious motion picture fi1m of how bubbles bump each other.
Our reasonableness did not arise, however, from a desire to keep peace with Bragg. Lying low made sense because we were up the creek with models based on sugar-phosphate cores. No matter how we looked at them, they smelled bad. On the day following the visit from King's, a hard look was given both to the ill-fated three-chain affair and to a number of possible variants. One couldn't be sure, but the impression was there that any model placing the sugar-phosphate backbone in the center of α-helix forced atoms closer together than the laws of chemistry allowed. Positioning one atom the proper distance from its neighbor often caused a distant atom to become jammed impossibly close to its partners.
A fresh start would be necessary to get the problem rolling again. Sadly, however, we realized that the impetuous tangle with King's would dry up our source of new experimental results. Subsequent invitations to the research colloquia were not to be expected, and even the most casual questioning of Maurice would provoke the suspicion that we were at it again. What was worse was the virtual certainty that cessation of model building on our part would not be accompanied by a burst of corresponding activity in their lab. So far, to our knowledge, King's had not built any threedimensional models of the necessary atoms. Nonetheless, our offer to speed that task by giving them the Cambridge molds for making the models was only halfheartedly received. Maurice did say, though, that within a few weeks someone might be found to put something together, and it was arranged that the next time one of us went down to London the jigs could be dropped off at their lab.
Thus the prospects that anyone on the British side of the Atlantic would crack DNA looked dim as the christmas holidays drew near. Though Francis went back to proteins, obliging Bragg by working on his thesis was not to his liking. Instead, after a few days of relative silence, he began to spout about super helical arrangements of the α-helix itse1f. Only during the lunch hour could I be sure that he would talk DNA. Fortunately, John Kendrew sensed that the moratorium on working on DNA did not extend to thinking about it. At no time did he try to reinterest me in myoglobin. Instead, I used the dark and chilly days to learn more theoretical chemistry or to leaf through journals, hoping that possibly there existed a forgotten clue to DNA.
The book I poked open the most was Francis' copy of The Nature of the Chemical Bond. Increasingly often, when Francis needed it to look up a crucial bond length, it would turn up on the quarter bench of lab space that John had given to me for experimental work. Somewhere in Pauling's masterpiece I hoped the real secret would lie. Thus Francis' gift to me of a second copy was a good omen. On the flyleaf was the inscription, "To Jim from Francis--christmas '51." The remnants of christianity were indeed useful (eg. "christmas tree")
No attempt was made to appeal the verdict. To the relief of Max and John, we refrained from publicly questioning Bragg's decision. An open outcry would reveal that our professor was completely in the dark about what the initials DNA stood for. There was no reason to believe that he gave it one hundredth the importance of the structure of metals, for which he took great delight in making soap-bubble mode1s. Nothing then gave Sir Lawrence more pleasure than showing his ingenious motion picture fi1m of how bubbles bump each other.
Our reasonableness did not arise, however, from a desire to keep peace with Bragg. Lying low made sense because we were up the creek with models based on sugar-phosphate cores. No matter how we looked at them, they smelled bad. On the day following the visit from King's, a hard look was given both to the ill-fated three-chain affair and to a number of possible variants. One couldn't be sure, but the impression was there that any model placing the sugar-phosphate backbone in the center of α-helix forced atoms closer together than the laws of chemistry allowed. Positioning one atom the proper distance from its neighbor often caused a distant atom to become jammed impossibly close to its partners.
A fresh start would be necessary to get the problem rolling again. Sadly, however, we realized that the impetuous tangle with King's would dry up our source of new experimental results. Subsequent invitations to the research colloquia were not to be expected, and even the most casual questioning of Maurice would provoke the suspicion that we were at it again. What was worse was the virtual certainty that cessation of model building on our part would not be accompanied by a burst of corresponding activity in their lab. So far, to our knowledge, King's had not built any threedimensional models of the necessary atoms. Nonetheless, our offer to speed that task by giving them the Cambridge molds for making the models was only halfheartedly received. Maurice did say, though, that within a few weeks someone might be found to put something together, and it was arranged that the next time one of us went down to London the jigs could be dropped off at their lab.
Thus the prospects that anyone on the British side of the Atlantic would crack DNA looked dim as the christmas holidays drew near. Though Francis went back to proteins, obliging Bragg by working on his thesis was not to his liking. Instead, after a few days of relative silence, he began to spout about super helical arrangements of the α-helix itse1f. Only during the lunch hour could I be sure that he would talk DNA. Fortunately, John Kendrew sensed that the moratorium on working on DNA did not extend to thinking about it. At no time did he try to reinterest me in myoglobin. Instead, I used the dark and chilly days to learn more theoretical chemistry or to leaf through journals, hoping that possibly there existed a forgotten clue to DNA.
The book I poked open the most was Francis' copy of The Nature of the Chemical Bond. Increasingly often, when Francis needed it to look up a crucial bond length, it would turn up on the quarter bench of lab space that John had given to me for experimental work. Somewhere in Pauling's masterpiece I hoped the real secret would lie. Thus Francis' gift to me of a second copy was a good omen. On the flyleaf was the inscription, "To Jim from Francis--christmas '51." The remnants of christianity were indeed useful (eg. "christmas tree")
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| Slavic Tree of life (with god-Perun) by Kriegerman |
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| World Tree and the Tree of Life among old Slavs |
15.
I DID not sit through the Christmas holidays in Cambridge. Avrion Mitchison had invited me to Carradale, the home of his parents, on the Mull of Kintyre. This was real luck, since over holidays Av's mother, Naomi, the distinguished writer, and his Labor MP father, Dick, were known to fill their large house with odd assortments of lively minds. Moreover, Naomi was a sister of England's most clever and eccentric biologist, J. B. S. Haldane. Neither the feeling that our DNA work had hit a road block nor the uncertainty of getting paid for the year was of much concern when I joined Av and his sister Val at Euston Station. No seats were left on the overnight Glasgow train, giving us a ten-hour journey seated on luggage listening to Val comment on the dull, boorish habits of the Americans who each year are deposited in increasing numbers at Oxford.
At Glasgow we found my sister Elizabeth, who had flown to Prestwick from Copenhagen. Two weeks previously she had sent a letter relating that she was pursued by a Dane. Instantly I sensed impending disaster, for he was a successful actor. At once I inquired whether I could bring Elizabeth to Carradale. The affirmative reply I received with much relief, since it was inconceivable that my sister could think about settling in Denmark after two weeks of an eccentric country house.
Dick Mitchison met the Campbell town bus at the turnoff for Carradale to drive us the final twenty hilly miles to the tiny Scottish fishing village where he and Naomi had lived for the past twenty years. Dinner was still going on as we emerged from a stone passage, which connected the gunroom with several larders, into a dining room dominated by sharp authoritative chatter. Av's zoologist brother Murdoch had already come, and he enjoyed cornering people to talk about how cells divide. More often, the theme was politics and the awkward cold war thought up by the American paranoids, who should be back in the law offices of middle western towns.
By the following morning I was aware that the best way not to feel impossibly cold was to remain in bed or when that proved impossible, to go walking, unless the rain was coming down in buckets. In the afternoons Dick was always trying to get someone to shoot pigeons, buy after one attempt, when I fired the gun after the pigeon were out of view, I took to lying on the drawing room floor as close as possible to the fire. There was also the warming diversion of going to the library to play ping-pong beneath Wyndham Lewis' stem drawings of Naomi and her children.
More than a week passed before I slowly caught on that a family of leftish leanings could be bothered by the way their guests dressed for dinner, but I put this aberrant behavior down as a sign of approaching old age. The thought never occurred to me that my own appearance was noticed, since my hair was beginning to lose its American identity. Odile had been very shocked when Max introduced me to her on my first day in Cambridge and afterwards had told Francis that a bald American was coming to work in the lab. The best way to rectify the situation was to avoid a barber until I merged with the Cambridge scene. Though my sister was upset when she saw me, I knew that months, if not years, might be required to replace her superficial values with those of the English intellectual. Carradale thus was the perfect environment to go one step further and acquire a beard. Admittedly I did not like its reddish color, but shaving with cold water was agony. Yet after a week of Val's and Murdoch's acid comments, together with the expected unpleasantness of my sister, I emerged for dinner with a clean face. When Naomi made a complimentary remark about my looks, I knew that I had made the right decision.
In the evenings there was no way to avoid intellectual games, which gave the greatest advantage to a large vocabulary. Every time my limpid contribution was read, I wanted to sink behind my chair rather than face the condescending stares of the Mitchison women. To my relief, the large number of house guests never permitted my turn to come often, and I made a point of sitting near the evening's box of chocolates, hoping no one would notice that I never passed it. Much more agreeable were the hours playing "Murder" in the dark twisting recesses of the upstairs floors. The most ruthless of the murder addicts was Av's sister Lois, then just back from teaching for a year in Karachi, and a firm proponent of the hypocrisy of Indian vegetable eaters.
Almost from the start of my stay I knew that I would depart from Naomi's and Dick's spectrum of the left with the greatest reluctance. The prospect of lunch with the alcoholic Eng1ish cider more than compensated for the habit of leaving the outside doors open to the westerly winds. My departure, three days after the New Year, nonetheless had been fixed by Murdoch's arranging for me to speak at a London meeting of the Society for Experimental Biology. Two days before my scheduled departure there was a heavy fall of snow, giving to the barren moors the look of Antarctic mountains. It was a perfect occasion for a long afternoon walk along the closed Campbelltown Road, with Av talking about his thesis experiments on the transplantation of immunity while I thought about the possibility that the road might remain impassable through the day I was to leave. The climate was not with me, however, for a group from the house caught the Clyde steamer at Tarbert and the next morning we were in London.
Upon my return to Cambridge I had expected to hear from the States about my fellowship, but there was no official communication to greet me. Since Luria had written me in November not to worry, the absence of firm news by now seemed ominous. Apparently no decision had been made and the worst was to be expected. The ax, however, could at most be only annoying. John and Max gave me assurance that a small English stipend could be dug up if I was completely cut off. Only in late January did my suspense end, with the arrival of a letter from Washington: I was sacked. The letter quoted the section of the fellowship award stating that the fellowship was valid only for work in the designated institution. My violation of this provision gave them no choice but to revoke the award.
The second paragraph gave the news that I had been awarded a completely new fellowship. I was not, however, to be let off merely with the long period of uncertainty. The second fellowship was not for the customary twelvemonth period but explicitly terminated after eight months, in the middle of May. My real punishment in not following the Board's advice and going to Stockholm was a thousand dollars. By this time it was virtually impossible to obtain any support which could begin before the September start of a new school year. I naturally accepted the fellowship. Two thousand dollars was not to, I be thrown away.
Less than a week later, a new letter came from Washington. It was signed by the same man, but not as head of the fellowship board. The hat he now displayed was that of the chairman of a committee of the National Research Counci1. A meeting was being arranged for which I was asked to give a lecture on the growth of viruses. The time of the meeting, to be held in Williamstown, was the middle of June, only a month after my fellowship would expire. I, of course, had not the slightest intention of leaving either in June or in September. The only problem was how to frame an answer. My first impulse was to write that I could not come because of an unforeseen financial disaster. But on second thought, 1 was against giving him the satisfaction of thinking he had affected my affairs. A letter went off: saying that I found Cambridge intellectually very exciting and so did not plan to be in the States by June.
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| (From Tolkien's trilogy) "The Trees Are Strong, My Lord... They have deep and strong roots!" |
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| Rainbow Saruman who hated "trees" but preferred dark-wild beasts... |
16.
BY now I had decided to mark time by working on tobacco mosaic virus (TMV). A vital component of TMV was nucleic acid, and so it was the perfect front to mask my continued interest in DNA. Admittedly the nucleic acid component was not DNA but a second form of nucleic acid known as ribonucleic acid (RNA). The difference was an advantage, however, since Maurice could lay no claim to RNA. If we solved RNA we might also provide the vital clue to DNA. On the other hand, TMV was thought to have a molecular weight of 40 million and at first glance should be frightfully more difficult to understand than the much smaller myoglobin and hemoglobin molecules that John and Max had been working on for years without obtaining any biologically interesting answers.
Moreover, TMV had previously been looked at with X-rays by J.D. Bernal and I. Fankuchen. This in itself was scary, since the scope of Bernal's brain was legendary and I could never hope to have his grasp of crystallographic theory. I was even unable to understand large sections of I their classic paper published just after the start of the war in the Journal of General Physiology. This was an odd place to publish, but Bernal had become absorbed in the war effort, and Fankuchen, by then returned to the States, decided to place their data in a journal looked at by people interested in viruses. After the war Fankuchen lost interest in viruses, and, though Bernal dabbled at protein crystallography, he was more concerned about furthering good relations with the Communist countries.
Though the theoretical basis for many of their conclusions was shaky, the take-home lesson was obvious. TMV was constructed from a large number of identical subunits. How the subunits were arranged they did not know. Moreover, 1939 was too early to come to grips with the fact that the protein and RNA components were likely to be constructed along radically different lines. By now, however, protein subunits were easy to imagine in large numbers. Just the opposite was true of RNA. Division of the RNA component into a large number of subunits would produce polynucleotid chains too small to carry the genetic information that Francis and I believed must reside in the viral RNA. The most plausible hypothesis for the TMV structure was a central RNA core surrounded by a large number of identical small protein sub units.
In fact, there already existed biochemical evidence for protein building blocks. Experiments of the German Gerhard Schramm, first published in 1944, reported that TMV particles in mild alkali fell apart into free RNA and a large number of similar, if not identical, protein molecules. Virtually no one outside Germany, however, thought that Schramm's story was right. This was because of the war. It was inconceivable to most people that the German beasts would have permitted the extensive experiments underlying his claims to be routinely carried out during the last years of a war they were so badly losing. It was all too easy to imagine that the work had direct Nazi support and that his experiments were incorrectly analyzed. Wasting time to' disprove Schramm was not to most biochemists' liking. As I read Bemal's paper, how ever, I suddenly became enthusiastic about Schramm, for, if he had misinterpreted his data, by accident he had hit upon the right answer.
Conceivably a few additional X-ray pictures would tell how the protein subunits were arranged. This was particularly true if they were helically stacked. Excitedly I pilfered Bemal's and Fankuchen's paper from the Philosophical Library and brought it up to the lab so that Francis could inspect the TMV.X-ray picture. When he saw the blank regions that characterize helical patterns, he jumped into action, quickly spilling out several possible helical TMV structures. From this moment on, I knew I could no longer avoid actually understanding the helical theory. Waiting until Francis had free time to help me would save me from having to master the mathematics, but only at the penalty of my standing still if Francis was out of the room. Luckily, merely a superficial grasp was needed to see why the TMV X-ray picture suggested a helix with a turn every 23 Å along the helical axis. The rules were, in fact, so simple that Francis considered writing them up under the title, "Fourier Transforms for the Birdwatcher."
This time, however, Francis did not carry the ball and on subsequent days maintained that the evidence for a TMV helix was only so-so. My morale automatically went down, until I hit upon a foolproof reason why subunits should be helically arranged. In a moment of after-supper boredom I had read a Faraday Society Discussion on "The Structure of Metals." It contained an ingenious theory by the theoretician F. C. Frank on how crystals grow. Every time the calculations were properly done, the paradoxical answer emerged that the crystals could not grow at anywhere near the observed rates. Frank saw that the paradox vanished if crystals were not as regular as suspected, but contained dislocations resulting in the perpetual presence of cozy corners into which new molecules could fit.
Several days later, on the bus to Oxford, the notion lD1e to me that each TMV particle should be thought of a tiny crystal growing like other crystals through the possession of cozy corners. Most important, the simplest way to generate cozy corners was to have the subunits helically arranged. The idea was so simple that it had to be right. Every helical staircase I saw that weekend in Oxford made me more confident that other biological structures would also have helical symmetry. For over a week I pored over electron micrographs of muscle and collagen fibers, looking for hints of helices. Francis, however, remained lukewarm, and in the absence of any hard facts I knew it was futile to try to bring him around.
Hugh Hux1ey came to my rescue by offering to teach me how to set up the X-ray camera for photographing TMV. The way to reveal a helix was to tilt the oriented TMV sample at several angles to the X-ray beam. Fankuchen had not done this, since before the war no one took helices seriously. I thus went to Roy Markham to see if y spare TMV was on hand. Markham then worked in the Molteno Institute, which, unlike all other Cambridge labs, was well heated. This unusual state came from the asthma of David Keilin, then the "Quick Professor" and Director of Molteno. I always welcomed an excuse to exist momentarily at 700 F, even though I was never sure when Markham would start the conversation by saying how bad I looked, implying that if I had been brought up on English beer I would not be in my sorry state. This time he was unexpectedly sympathetic and without hesitation volunteered some virus. The idea of Francis and me dirtying our hands with experiments brought unconcealed amusement.
My first X-ray pictures revealed, not unexpectedly, much less detail than was found in the published pictures. Over a month was required before I could get even half way presentable pictures. They were still a long way, though, from being good enough to spot α-helix. The only real fun during February came from a costume party given by Geoffrey Roughton at his parents' home on Adams Road. Surprisingly, Francis did not wish to go, even though Geoffrey knew many pretty girls and was said to write poetry wearing one earring. Odile, however, did not want to miss it, so I went with her after hiring a Restoration soldier's garb. The moment we edged through the door into the crush of half drunken dancers we knew the evening would be a smashing success, since seemingly half the attractive Cambridge au pair girls (foreign girls living with English families) were there.
A week later there was a Tropical Night Ball that Odile was keen to attend, both since she had done the decorations and because it was sponsored by black people. Francis again demurred, this time wisely. The dance floor was half vacant, and even after several long drinks I did not enjoy dancing badly in open view. More to the point was that Linus Pauling was coming to London in May for a meeting organized by the Royal Society on the structure of proteins. One could never be sure where he would strike next. Particularly chilling was the prospect that he would ask to visit King's.
Moreover, TMV had previously been looked at with X-rays by J.D. Bernal and I. Fankuchen. This in itself was scary, since the scope of Bernal's brain was legendary and I could never hope to have his grasp of crystallographic theory. I was even unable to understand large sections of I their classic paper published just after the start of the war in the Journal of General Physiology. This was an odd place to publish, but Bernal had become absorbed in the war effort, and Fankuchen, by then returned to the States, decided to place their data in a journal looked at by people interested in viruses. After the war Fankuchen lost interest in viruses, and, though Bernal dabbled at protein crystallography, he was more concerned about furthering good relations with the Communist countries.
Though the theoretical basis for many of their conclusions was shaky, the take-home lesson was obvious. TMV was constructed from a large number of identical subunits. How the subunits were arranged they did not know. Moreover, 1939 was too early to come to grips with the fact that the protein and RNA components were likely to be constructed along radically different lines. By now, however, protein subunits were easy to imagine in large numbers. Just the opposite was true of RNA. Division of the RNA component into a large number of subunits would produce polynucleotid chains too small to carry the genetic information that Francis and I believed must reside in the viral RNA. The most plausible hypothesis for the TMV structure was a central RNA core surrounded by a large number of identical small protein sub units.
In fact, there already existed biochemical evidence for protein building blocks. Experiments of the German Gerhard Schramm, first published in 1944, reported that TMV particles in mild alkali fell apart into free RNA and a large number of similar, if not identical, protein molecules. Virtually no one outside Germany, however, thought that Schramm's story was right. This was because of the war. It was inconceivable to most people that the German beasts would have permitted the extensive experiments underlying his claims to be routinely carried out during the last years of a war they were so badly losing. It was all too easy to imagine that the work had direct Nazi support and that his experiments were incorrectly analyzed. Wasting time to' disprove Schramm was not to most biochemists' liking. As I read Bemal's paper, how ever, I suddenly became enthusiastic about Schramm, for, if he had misinterpreted his data, by accident he had hit upon the right answer.
Conceivably a few additional X-ray pictures would tell how the protein subunits were arranged. This was particularly true if they were helically stacked. Excitedly I pilfered Bemal's and Fankuchen's paper from the Philosophical Library and brought it up to the lab so that Francis could inspect the TMV.X-ray picture. When he saw the blank regions that characterize helical patterns, he jumped into action, quickly spilling out several possible helical TMV structures. From this moment on, I knew I could no longer avoid actually understanding the helical theory. Waiting until Francis had free time to help me would save me from having to master the mathematics, but only at the penalty of my standing still if Francis was out of the room. Luckily, merely a superficial grasp was needed to see why the TMV X-ray picture suggested a helix with a turn every 23 Å along the helical axis. The rules were, in fact, so simple that Francis considered writing them up under the title, "Fourier Transforms for the Birdwatcher."
This time, however, Francis did not carry the ball and on subsequent days maintained that the evidence for a TMV helix was only so-so. My morale automatically went down, until I hit upon a foolproof reason why subunits should be helically arranged. In a moment of after-supper boredom I had read a Faraday Society Discussion on "The Structure of Metals." It contained an ingenious theory by the theoretician F. C. Frank on how crystals grow. Every time the calculations were properly done, the paradoxical answer emerged that the crystals could not grow at anywhere near the observed rates. Frank saw that the paradox vanished if crystals were not as regular as suspected, but contained dislocations resulting in the perpetual presence of cozy corners into which new molecules could fit.
Several days later, on the bus to Oxford, the notion lD1e to me that each TMV particle should be thought of a tiny crystal growing like other crystals through the possession of cozy corners. Most important, the simplest way to generate cozy corners was to have the subunits helically arranged. The idea was so simple that it had to be right. Every helical staircase I saw that weekend in Oxford made me more confident that other biological structures would also have helical symmetry. For over a week I pored over electron micrographs of muscle and collagen fibers, looking for hints of helices. Francis, however, remained lukewarm, and in the absence of any hard facts I knew it was futile to try to bring him around.
Hugh Hux1ey came to my rescue by offering to teach me how to set up the X-ray camera for photographing TMV. The way to reveal a helix was to tilt the oriented TMV sample at several angles to the X-ray beam. Fankuchen had not done this, since before the war no one took helices seriously. I thus went to Roy Markham to see if y spare TMV was on hand. Markham then worked in the Molteno Institute, which, unlike all other Cambridge labs, was well heated. This unusual state came from the asthma of David Keilin, then the "Quick Professor" and Director of Molteno. I always welcomed an excuse to exist momentarily at 700 F, even though I was never sure when Markham would start the conversation by saying how bad I looked, implying that if I had been brought up on English beer I would not be in my sorry state. This time he was unexpectedly sympathetic and without hesitation volunteered some virus. The idea of Francis and me dirtying our hands with experiments brought unconcealed amusement.
My first X-ray pictures revealed, not unexpectedly, much less detail than was found in the published pictures. Over a month was required before I could get even half way presentable pictures. They were still a long way, though, from being good enough to spot α-helix. The only real fun during February came from a costume party given by Geoffrey Roughton at his parents' home on Adams Road. Surprisingly, Francis did not wish to go, even though Geoffrey knew many pretty girls and was said to write poetry wearing one earring. Odile, however, did not want to miss it, so I went with her after hiring a Restoration soldier's garb. The moment we edged through the door into the crush of half drunken dancers we knew the evening would be a smashing success, since seemingly half the attractive Cambridge au pair girls (foreign girls living with English families) were there.
A week later there was a Tropical Night Ball that Odile was keen to attend, both since she had done the decorations and because it was sponsored by black people. Francis again demurred, this time wisely. The dance floor was half vacant, and even after several long drinks I did not enjoy dancing badly in open view. More to the point was that Linus Pauling was coming to London in May for a meeting organized by the Royal Society on the structure of proteins. One could never be sure where he would strike next. Particularly chilling was the prospect that he would ask to visit King's.
___________________________________
End of part 1 of 2
( to be continued...)
End of part 1 of 2
( to be continued...)
 |
| James Dewey Watson |
James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick and Rosalind Franklin. Watson, Crick, and Maurice Wilkins were awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".
Watson earned degrees at the University of Chicago (BS, 1947) and Indiana University (PhD, 1950). Following a post-doctoral year at the University of Copenhagen with Herman Kalckar and Ole Maaloe, later Watson worked at the University of Cambridge's Cavendish Laboratory in England, where he first met his future collaborator and friend Francis Crick.
From 1956 to 1976, Watson was on the faculty of the Harvard University Biology Department, promoting research in molecular biology. From 1968 he served as director of Cold Spring Harbor Laboratory (CSHL), greatly expanding its level of funding and research. At CSHL, he shifted his research emphasis to the study of cancer, along with making it a world leading research center in molecular biology. In 1994, he started as president and served for 10 years. He was then appointed chancellor, serving until he resigned in 2007 after making controversial comments claiming a link between intelligence and race. Between 1988 and 1992, Watson was associated with the National Institutes of Health, helping to establish the Human Genome Project.
Watson has written many science books, including the textbook Molecular Biology of the Gene (1965) and his bestselling book The Double Helix (1968).
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