"The Double Helix: A Personal Account of the Discovery of the Structure of DNA" ~ James D. Watson (Part 2 of 2)
Part 2 (the last)
Part 1 - Here*
Part 1 - Here*
17.
LINUS, however, was blocked from descending on London. The State Department did not want troublemakers like Pauling wandering about the globe saying nasty things about the politics of its onetime investment bankers who held back the hordes of godless Reds. Failure to contain Pauling might result in a London press conference with Linus expounding peaceful coexistence. Acheson's position was harassed enough without ling McCarthy the opportunity to announce that our government let radicals protected by U.S. passports set ck the American way of life. Francis and I were already in London when the scan I reached the Royal Society. The reaction was one of almost complete disbelief. It was far more reassuring to go on imagining that Linus had taken ill on the plane to New York. The failure to let one of the world's leading scientists attend a completely nonpolitical meeting would have been expected from the Russians. A first-rate Russian might easily abscond to the more affluent West. No danger existed, however, that Linus might want to flee. Only complete satisfaction with their Cal Tech existence me from him and his family.
Several members of Cal Tech's governing board, however, would have been delighted with his voluntary departure. Every time they picked up a newspaper and saw Pauling's name among the sponsors of the World Peace Conference they seethed with rage, wishing there were a way to rid Southern California of his pernicious charm. But Linus knew better than to expect more than confused anger from the self-made California millionaires whose knowledge of foreign policy was formed largely by the Los Angeles Times. The debacle was no surprise to several of us who had just been in Oxford for a Society of General Microbiology meeting on "The Nature of Viral Multiplication." One of the main speakers was to have been Luria. Two weeks prior to his scheduled flight to London, he was notified that he would not get a passport. As usual, the State Department would not come clean about what it considered dirt.
Luria's absence thrust upon me the job of describing the recent experiments of the American phage workers. There was no need to put together a speech. Several days before the meeting, Al Hershey had sent me a long letter from Cold Spring Harbor summarizing the recently completed experiments by which he and Martha Chase established that a key feature of the infection of a bacterium by a phage was the injection of the viral DNA into the host bacterium. Most important, very little protein entered the bacterium. Their experiment was thus a powerful new proof that DNA is the primary genetic material. Nonetheless, almost no one in the audience of over four hundred microbiologists seemed interested as I read long sections of Hershey's letter Obvious exceptions were André Lwoff, Seymour Benzer, and Gunther Stent, all briefly over from Paris. They knew that Hershey's experiments were not trivial and that from then on everyone was going to place more emphasis on DNA. To most of the spectators, however, Hershey's name carried no weight. Moreover, when it came out that I was an American, my uncut hair provided no assurance that my scientific judgment was not equally bizarre.
Dominating the meeting were the English plant virologists F. C. Bawden and N. W. Pirie. No one could match the smooth erudition of Bawden or the assured nihilism of Pirie, who strongly disliked the notion that some phages have tails or that TMV is of fixed length. When I tried to comer Pirie about Schramm's experiments he said they should be dismissed, and so I retreated to the politically less controversial point of whether the 3000 Ǻ length of many TMV particles was biologically important. The idea that a simple answer was preferable had no appeal to Pirie, who knew that viruses were too large to have well-defined structures. If it had not been for the presence of Lwoff, the meeting would have flopped totally. André was very keen about the role of divalent metals in phage multiplication and so was receptive to my belief that ions were decisively important for nucleic-acid structure. Especially in 19uing was his hunch that specific ions might be the trick for the exact copying of macromolecules or the attraction between similar chromosomes. There was no way test our dreams, however, unless Rosy did an about-face from her determination to rely completely on classical X-ray diffraction techniques.
At the Royal Society Meeting there was no hint that anyone at King's had mentioned ions since the confrontation with Francis and me in early December. Upon pressing Maurice, I learned that the jigs for the molecular models had not been touched after arriving at his lab. The time had not yet come to press Rosy and Gosling about building models. If anything, the squabbling between Maurice and Rosy was more bitter than before the visit to Cambridge. Now she was insisting that her data told her DNA was not a he1ix. Rather than build helical models at Maurice's command, she might twist the copper-wire models about his neck. When Maurice asked whether we needed the molds In Cambridge, we said yes, half implying that more carbon atoms were needed to make models showing how polypeptide chains turned comers. To my relief, Maurice as very open about what was not happening at King's. The fact that I was doing serious X-ray work with TMV gave him assurance that I should not soon again become preoccupied with the DNA pattern.
Several members of Cal Tech's governing board, however, would have been delighted with his voluntary departure. Every time they picked up a newspaper and saw Pauling's name among the sponsors of the World Peace Conference they seethed with rage, wishing there were a way to rid Southern California of his pernicious charm. But Linus knew better than to expect more than confused anger from the self-made California millionaires whose knowledge of foreign policy was formed largely by the Los Angeles Times. The debacle was no surprise to several of us who had just been in Oxford for a Society of General Microbiology meeting on "The Nature of Viral Multiplication." One of the main speakers was to have been Luria. Two weeks prior to his scheduled flight to London, he was notified that he would not get a passport. As usual, the State Department would not come clean about what it considered dirt.
Luria's absence thrust upon me the job of describing the recent experiments of the American phage workers. There was no need to put together a speech. Several days before the meeting, Al Hershey had sent me a long letter from Cold Spring Harbor summarizing the recently completed experiments by which he and Martha Chase established that a key feature of the infection of a bacterium by a phage was the injection of the viral DNA into the host bacterium. Most important, very little protein entered the bacterium. Their experiment was thus a powerful new proof that DNA is the primary genetic material. Nonetheless, almost no one in the audience of over four hundred microbiologists seemed interested as I read long sections of Hershey's letter Obvious exceptions were André Lwoff, Seymour Benzer, and Gunther Stent, all briefly over from Paris. They knew that Hershey's experiments were not trivial and that from then on everyone was going to place more emphasis on DNA. To most of the spectators, however, Hershey's name carried no weight. Moreover, when it came out that I was an American, my uncut hair provided no assurance that my scientific judgment was not equally bizarre.
Dominating the meeting were the English plant virologists F. C. Bawden and N. W. Pirie. No one could match the smooth erudition of Bawden or the assured nihilism of Pirie, who strongly disliked the notion that some phages have tails or that TMV is of fixed length. When I tried to comer Pirie about Schramm's experiments he said they should be dismissed, and so I retreated to the politically less controversial point of whether the 3000 Ǻ length of many TMV particles was biologically important. The idea that a simple answer was preferable had no appeal to Pirie, who knew that viruses were too large to have well-defined structures. If it had not been for the presence of Lwoff, the meeting would have flopped totally. André was very keen about the role of divalent metals in phage multiplication and so was receptive to my belief that ions were decisively important for nucleic-acid structure. Especially in 19uing was his hunch that specific ions might be the trick for the exact copying of macromolecules or the attraction between similar chromosomes. There was no way test our dreams, however, unless Rosy did an about-face from her determination to rely completely on classical X-ray diffraction techniques.
At the Royal Society Meeting there was no hint that anyone at King's had mentioned ions since the confrontation with Francis and me in early December. Upon pressing Maurice, I learned that the jigs for the molecular models had not been touched after arriving at his lab. The time had not yet come to press Rosy and Gosling about building models. If anything, the squabbling between Maurice and Rosy was more bitter than before the visit to Cambridge. Now she was insisting that her data told her DNA was not a he1ix. Rather than build helical models at Maurice's command, she might twist the copper-wire models about his neck. When Maurice asked whether we needed the molds In Cambridge, we said yes, half implying that more carbon atoms were needed to make models showing how polypeptide chains turned comers. To my relief, Maurice as very open about what was not happening at King's. The fact that I was doing serious X-ray work with TMV gave him assurance that I should not soon again become preoccupied with the DNA pattern.
 |
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18.
MAURICE had no suspicion that almost immediately I would get the X-ray pattern needed to prove that TMV, was helical. My unexpected success came from using a powerful rotating anode X-ray tube which had just been assembled in the Cavendish. This supertube permitted me 1 1to take pictures twenty times faster than with conventional equipment. Within a week I more than doubled the number of my TMV photographs. Custom then locked the doors of the Cavendish at 10:00 P.M. Though the porter had a flat next to the gate, no one disturbed him after the closing hour. Rutherford had believed in discouraging students from night work, since the summer evenings were more suitable for tennis. Even fifteen years after his death there was only one key available for late workers. This was now pre-empted by Hugh Huxley, who argued that muscle fibers were living and hence not subject to rules for physicists. When necessary, he lent me the key or walked down the stair to unlock the heavy doors that led out onto Free School Lane.
Hugh was not in the lab when late on a midsummer June night I went back to shut down the X-ray tube and to develop the photograph of a new TMV sample. It was tilted at about 25 degrees, so that if I were lucky I'd find the helical reflections. The moment I held the still wet negative against the light box, I knew we had it. The tell tale helical markings were unmistakable. Now there should be no problem in persuading Luria and Delbrück that my staying in Cambridge made sense. Despite the midnight hour, I had no desire to go back to my room on Tennis Court Road, and happily I walked along the backs, for over an hour. The following morning I anxiously awaited Francis' arrival to confirm the helical diagnosis. When he needed less than I ten seconds to spot the crucial reflection, all my lingering doubts vanished. In fun I went on to trap Francis into believing that I did not think my X-ray picture was in fact very critica1. Instead, I argued that the really important step was the cozy-corner insight. These flippant words were hardly out of my mouth before Francis was off on the dangers of uncritical teleology. Francis always said what he meant and assumed that I acted the same way. Though success in Cam bridge conversation frequently came from saying something preposterous, hoping that someone would take you seriously, there was no need for Francis to adopt this gambit. A discourse of only one or two minutes on the emotional problems of foreign girls was always sufficient tonic for even the most staid Cambridge evening.
It was, of course, clear what we should next conquer. No more dividends could come quickly from TMV. Further unraveling of its detailed structure needed a more professional attack than I could muster. Moreover, it was not obvious that even the most backbreaking effort would give within several years the structure of the RNA component. The way to DNA was not through TMV. The moment was thus appropriate to think seriously about some curious regularities in DNA chemistry first observed at Columbia by the Austrian-born biochemist Erwin Chargaff. Since the war, Chargaff and his students had been painstakingly analyzing various DNA samples for the relative proportions of their purine and pyrimidine bases. In all their DNA preparations the number of adenine ( A ) molecules was very similar to the number of thymine (T) molecules, while the number of guanine (G) molecules was very close to the number of cytosine (C) molecules. Moreover, the proportion of adenine and thymine groups varied with their biological origin. The DNA of some organisms had an excess of A and T, while in other forms of life there was an excess of G and C. No explanation for his striking results was offered by Chargaff, though he obviously thought they were significant. When I first reported them to Francis they did not ring a bell, and he went on thinking about other matters.
Hugh was not in the lab when late on a midsummer June night I went back to shut down the X-ray tube and to develop the photograph of a new TMV sample. It was tilted at about 25 degrees, so that if I were lucky I'd find the helical reflections. The moment I held the still wet negative against the light box, I knew we had it. The tell tale helical markings were unmistakable. Now there should be no problem in persuading Luria and Delbrück that my staying in Cambridge made sense. Despite the midnight hour, I had no desire to go back to my room on Tennis Court Road, and happily I walked along the backs, for over an hour. The following morning I anxiously awaited Francis' arrival to confirm the helical diagnosis. When he needed less than I ten seconds to spot the crucial reflection, all my lingering doubts vanished. In fun I went on to trap Francis into believing that I did not think my X-ray picture was in fact very critica1. Instead, I argued that the really important step was the cozy-corner insight. These flippant words were hardly out of my mouth before Francis was off on the dangers of uncritical teleology. Francis always said what he meant and assumed that I acted the same way. Though success in Cam bridge conversation frequently came from saying something preposterous, hoping that someone would take you seriously, there was no need for Francis to adopt this gambit. A discourse of only one or two minutes on the emotional problems of foreign girls was always sufficient tonic for even the most staid Cambridge evening.
It was, of course, clear what we should next conquer. No more dividends could come quickly from TMV. Further unraveling of its detailed structure needed a more professional attack than I could muster. Moreover, it was not obvious that even the most backbreaking effort would give within several years the structure of the RNA component. The way to DNA was not through TMV. The moment was thus appropriate to think seriously about some curious regularities in DNA chemistry first observed at Columbia by the Austrian-born biochemist Erwin Chargaff. Since the war, Chargaff and his students had been painstakingly analyzing various DNA samples for the relative proportions of their purine and pyrimidine bases. In all their DNA preparations the number of adenine ( A ) molecules was very similar to the number of thymine (T) molecules, while the number of guanine (G) molecules was very close to the number of cytosine (C) molecules. Moreover, the proportion of adenine and thymine groups varied with their biological origin. The DNA of some organisms had an excess of A and T, while in other forms of life there was an excess of G and C. No explanation for his striking results was offered by Chargaff, though he obviously thought they were significant. When I first reported them to Francis they did not ring a bell, and he went on thinking about other matters.
Soon afterwards, however, the suspicion that the regularities were important clicked inside his head as the result of several conversations with the young theoretical chemist John Griffith. One occurred while they were drinking beer after an evening ta1k by the astronomer Tommy Gold on "the perfect cosmological principle. Tommy's facility for making a far-out idea seem plausible set Francis to wondering whether an argument could be made for a "perfect biological principle." Knowing that Griffith was interested in theoretical schemes for gene replication, he popped out with the idea that the perfect biologica1 principle was the self-replication of the gene that is, the ability of a gene to be exactly copied when the chromosome number doubles during cell division. Griffith, however, did not go along, since for some months he had preferred a scheme where gene copying was based upon the a1temative formation of complementary surfaces.
This was not an origina1 hypothesis. It had been floating about for almost thirty years in the circle of theoretically inclined geneticists intrigued by gene duplication. The argument went that gene duplication required the formation of a complementary (negative) image where shape was related to the original (positive) surface like a lock to a key. The complementary negative image would then function as the mold (template) for the synthesis of a new positive image. A smaller number of geneticists, however, ba1ked at complementary replication. Prominent among them was H. J. Muller, who was impressed that severa1 well-known theoretica1 physicists, especially Pascua1 Jordan, thought forces existed by which like attracted like. But Pauling abhorred this direct mechanism and was especially irritated by the suggestion that it was supported by quantum mechanics. Just before the war, he I asked Delbrück (who had drawn his attention to Jordan's papers) to coauthor a note to Science firmly stating that quantum mechanics favored a geneduplicating mechanism involving the synthesis of complementary replicas.
Neither Francis nor Griffith was long satisfied that evening by restatements of well-worn hypotheses. Both knew that the important task was now to pinpoint the attractive forces. Here Francis forcefully argued that specific hydrogen bonds were not the answer. They could not provide the necessary exact specificity, since our chemist friends repeatedly told us that the hydrogen atoms in the purine and pyrimidine bases did not have fixed locations but, randomly moved from one spot to another. Instead, Francis had the feeling that DNA replication involved specific attractive forces between the flat surfaces of the bases.
Luckily, this was the sort of force that Griffith might just be able to calculate. If the complementary scheme was right, he might find attractive forces between bases with different structures. On the other hand, if direct copy existed, his calculations might reveal attraction between identical bases. Thus, at the closing hour they parted with the understanding that Griffith would see if the calculations were feasible. Several days later, when they bumped into each other in the Cavendish tea queue, Francis learned that a semirigorous argument hinted that adenine and thymine should stick to each other by their surfaces. A similar argument could be put forward for attractive forces between guanine and cytosine.
Francis immediately jumped at the answer. If his memory served him right, these were the pairs of bases that Chargaff had shown to occur in equal amounts. Excitedly told Griffith that I had recently muttered to him some odd results of Chargaff's. At the moment, though, he wasn't sure that the same base pairs were involved. But soon as the data were checked he would drop by Griffith's rooms to set him straight. At lunch I confirmed that Francis had got Chargaff's results right. But by then he was only routinely enthusiastic as he went over Griffith's quantum mechanical arguments. For one thing, Griffith, when pressed, did not want to defend his exact reasoning too strongly. Too many variables had been ignored to make the calculations possible in a reasonable time. Moreover, though each base has two flat sides, no explanation existed for why only one side would be chosen. And there was no reason ruling out the idea that Chargaff's regularities had their origin in the genetic code. In some way specific groups of nucleotides must code for specific amino 'acids. Conceivably, adenine equaled thymine because of a yet undiscovered role in the ordering of the bases. There was addition Roy Markham's assurance that, if Chargaff said that guanine equaled cytosine, he was equally certain did not. In Markham's eyes, Chargaff's experimental methods inevitably underestimated the true amount of cytosine.
Nonetheless, Francis was not yet ready to dump Griffit’s scheme when, early in July, John Kendrew walked into our newly acquired office to tell us that Chargaff himself would soon be in Cambridge for an evening. John had arranged for him to have dinner at Peterhouse, and Francis and I were invited to join them later for drinks in John's room. At High Table John kept the conversation away from serious matters, letting loose only the possibility that Francis and I were going to solve the DNA structure by model building. Chargaff, as one of the world's experts on DNA, was at first not amused by dark horses trying to win the race. Only when John reassured him by mentioning that I was not a typical American did he realize that he was about to listen to a nut. Seeing me quickly reinforced his intuition. Immediately he derided my hair and accent, for since I came from Chicago I had no right to act otherwise. Blandly telling him that I kept my hair long to avoid confusion with American Air Force personnel proved my mental instability. The high point in Chargaff's scorn came when he led I Francis into admitting that he did not remember the chemical differences among the four bases. The faux pas slipped out when Francis mentioned Griffith's calculations. Not remembering which of the bases had amino groups, he could not qualitatively describe the quantum mechanical argument until he asked Chargaff to write out their formulas. Francis' subsequent retort that he could always look them up got nowhere in persuading Chargaff that we knew where we were going or how to get there.
But regardless of what went through Chargaff's sarcastic mind, someone had to explain his results. Thus the next afternoon Francis buzzed over to Griffith's rooms in Trinity to set himself straight about the base-pair data. Hearing "Come in," he opened the door to see Griffith and a girl. Realizing that this was not the moment for science, he slowly retreated, asking Griffith to tell him again the pairs produced by his calculations. After scribbling them down on the back of an envelope, he left. Since I had departed that morning for the continent, his next stop was the Philosophical Library, where he could remove his lingering doubts about Chargaff's data. Then with both sets of information firmly in hand, he considered returning the next day to Griffith's rooms. But on second thought he realized that Griffith's interests were elsewhere. It was all too clear that the presence of popsies does not inevitably lead to a scientific future.
 |
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19.
Two weeks later Chargaff and I glanced at each other in Paris. Both of us were there for the International Bio chemical Congress. A trace of a sardonic smile was ail the recognition I got when we passed in the courtyard outside the massive Salle Richelieu of the Sorbonne. That day I was tracking down Max Delbrück. Before I had left Copenhagen for Cambridge, he had offered me a research position in the biology division of Cal Tech and arranged a Polio Foundation fellowship, to start in September 1952. This March, however, I had written Delbrück that I wanted another Cambridge year. Without any 'hesitation he saw to it that my forthcoming fellowship was transferred to the Cavendish. Delbrück's speedy approval pleased me, for he had ambivalent feelings about the ultimate value to biology of Pauling-like structural studies. With the helical TMV picture now in my pocket, I felt more confident that Delbrück would at last wholeheartedly approve my liking for Cambridge. A few minutes' conversation, nonetheless, revealed no basic change in his outlook. Almost no comments emerged from Delbrück as I outlined how TMV was put together. The same indifferent response accompanied my hurriedly delivered summary of our attempts to get DNA by model building. Delbrück was drawn out only by my remark that Francis was exceedingly bright. Unfortunately, I went on to liken Francis' way of thinking to Pauling's. But in Delbrück's world no chemical thought matched the power of a genetic cross. Later that evening, when the geneticist Boris Ephrussi brought up my love affair with Cambridge, Delbrück threw up his hands in disgust.
The sensation of the meeting was the unexpected appearance of Linus. Possibly because there had been considerable newspaper play on the withdrawal of his pass port, the State Department reversed itself and allowed Linus to show off the α-helix. A lecture was hastily arranged for the session at which Perutz spoke. Despite the short notice, an overflow crowd was on hand, hoping that they would be the first to learn of a new inspiration. Pauling’s talk, however, was only a humorous rehash of published ideas. It nonetheless satisfied everybody, except the few of us who knew his recent papers backward and forward. No new fireworks went off, nor was there any indication given about what now occupied his mind. After his lecture, swarms of admirers surrounded him, and I didn't have the courage to break in before he and his wife, Ava Helen, went back to the nearby Trianon Hotel.
Maurice was about, looking somewhat sour. He had stopped over on his way to Brazil, where he was to lecture for a month on biophysics. His presence surprised me, since it was against his character to seek the trauma of watching two thousand bread-and-butter biochemists pile in and out of badly lighted baroque lecture halls. Speaking down to the cobblestones, he asked me whether I found the talks as tedious as he did. A few academics like Jacques Monod and Sol Spiegelman were enthusiastic speakers, but generally there was so much droning that he found it hard to stay alert for the new facts he should pick up. tried to rescue Maurice's morale by bringing him out to the Abbaye at Royaumont for the weeklong meeting on phage following the biochemical congress. Though his departure for Rio would limit him to only a night's stay, he liked the idea of meeting the people who did clever biological experiments about DNA. In the train going to Royaumont, however, he looked off-color, giving no indication of wanting either to read The Times or to hear me gossip about the phage group. After we were fixed with beds in the high-ceilinged rooms of the partially restored Cistercian monastery, I began talking with some friends I had not seen since leaving the States. Later I kept expecting Maurice to search me out, and when he missed dinner I went up to his room. There I found him lying flat on his stomach, hiding his face from the dim light I had turned on. Something eaten in Paris had not gone down properly, but he told me not to be bothered. The following morning I was given a note saying that he had recovered but had to catch the early train to Paris and apologizing for the trouble he had given me.
Later that morning Lwoff mentioned that Pauling was coming out for a few hours the next day. Immediately I began to think of ways that would allow me to sit next to him at lunch. His visit, however, bore no relation to science. Jeffries Wyman, our scientific attaché in Paris and an acquaintance of Pauling's, thought that Linus and Ava Helen would enjoy the austere charm of the thirteenth century buildings. During a break in the morning session I caught sight of Wyman's bony, aristocratic face in search of André Lwoff. The Paulings were here and soon began talking to the Delbrücks. Brietly I had Linus to myself after Delbrück mentioned that twelve months, hence I was coming to Cal Tech. Our conversation centered on the possibility that at Pasadena I might continue X-ray work with viruses. Virtually no words went to DNA. When I brought up the X-ray pictures at King's, Linus gave the opinion that very accurate X-ray work of the type done by his associates on amino acids was vital to our eventual understanding of the nucleic acids. I got much further with Ava Helen. Learning that I would be in Cambridge next year, she talked about her son Peter. Already I knew that Peter was accepted by Bragg to work toward a Ph.D. with John Kendrew. This was despite the fact that his Cal Tech grades left much to be desired, even considering his long bout with mononucleosis. John, however, did not want to challenge Linus' desire to place Peter with him, especially knowing that he and his beautiful blonde sister gave smashing parties. Peter and Linda, if she were to visit him, would undoubtedly liven up the Cambridge scene. Then the dream of virtually every Cal Tech chemistry student was that Linda would make his reputation by marrying him. The scuttlebutt about Peter centered on girls and was confused. But now Ava Helen gave me the dope that Peter was an exceptionally fine boy whom everybody would enjoy having around as much as she did. All the same, I remained silently unconvinced that Peter would add as much to our lab as Linda. When Linus beckoned that they must go, I told Ava Helen that I would help her son adjust to the restricted life of the Cambridge research student.
A garden party at Sans Souci, the country home of the Baroness Edmond de Rothschild, effectively brought the meeting to its end. Dressing was no easy matter for me. Just before the biochemical congress all my belongings were snatched from my train compartment as I was sleeping. Except for a few items picked up at an army PX, the clothes I still possessed had been chosen for a subsequent visit to the Italian Alps. While I felt ease giving my talk on TMV in shorts, the French contingent feared that I would go one step further by arriving at Sans Souci in the same outfit. A borrowed jacket and tie, however, made me superficially presentable as our bus driver let us out in front of the huge country house. Sol Spiegelman and I went straight for a butler carrying smoked salmon and champagne, and after a few minutes sensed the value of a cultivated aristocracy. Just before we were to reboard the bus, I wandered into the large drawing room dominated by a Hals and a Rubens. The Baroness was telling several visitors how pleased she was to have such distinguished guests. She did regret, however, that the mad Englishman from Cambridge decided not to come and enliven the mood. For an instant I was puzzled, until I realized that Lwoff had thought it prudent to warn the Baroness about an unclothed guest who might prove eccentric. The message of my first meeting with the aristocracy was clear. I would not be invited back if I acted like everyone else.
The sensation of the meeting was the unexpected appearance of Linus. Possibly because there had been considerable newspaper play on the withdrawal of his pass port, the State Department reversed itself and allowed Linus to show off the α-helix. A lecture was hastily arranged for the session at which Perutz spoke. Despite the short notice, an overflow crowd was on hand, hoping that they would be the first to learn of a new inspiration. Pauling’s talk, however, was only a humorous rehash of published ideas. It nonetheless satisfied everybody, except the few of us who knew his recent papers backward and forward. No new fireworks went off, nor was there any indication given about what now occupied his mind. After his lecture, swarms of admirers surrounded him, and I didn't have the courage to break in before he and his wife, Ava Helen, went back to the nearby Trianon Hotel.
Maurice was about, looking somewhat sour. He had stopped over on his way to Brazil, where he was to lecture for a month on biophysics. His presence surprised me, since it was against his character to seek the trauma of watching two thousand bread-and-butter biochemists pile in and out of badly lighted baroque lecture halls. Speaking down to the cobblestones, he asked me whether I found the talks as tedious as he did. A few academics like Jacques Monod and Sol Spiegelman were enthusiastic speakers, but generally there was so much droning that he found it hard to stay alert for the new facts he should pick up. tried to rescue Maurice's morale by bringing him out to the Abbaye at Royaumont for the weeklong meeting on phage following the biochemical congress. Though his departure for Rio would limit him to only a night's stay, he liked the idea of meeting the people who did clever biological experiments about DNA. In the train going to Royaumont, however, he looked off-color, giving no indication of wanting either to read The Times or to hear me gossip about the phage group. After we were fixed with beds in the high-ceilinged rooms of the partially restored Cistercian monastery, I began talking with some friends I had not seen since leaving the States. Later I kept expecting Maurice to search me out, and when he missed dinner I went up to his room. There I found him lying flat on his stomach, hiding his face from the dim light I had turned on. Something eaten in Paris had not gone down properly, but he told me not to be bothered. The following morning I was given a note saying that he had recovered but had to catch the early train to Paris and apologizing for the trouble he had given me.
Later that morning Lwoff mentioned that Pauling was coming out for a few hours the next day. Immediately I began to think of ways that would allow me to sit next to him at lunch. His visit, however, bore no relation to science. Jeffries Wyman, our scientific attaché in Paris and an acquaintance of Pauling's, thought that Linus and Ava Helen would enjoy the austere charm of the thirteenth century buildings. During a break in the morning session I caught sight of Wyman's bony, aristocratic face in search of André Lwoff. The Paulings were here and soon began talking to the Delbrücks. Brietly I had Linus to myself after Delbrück mentioned that twelve months, hence I was coming to Cal Tech. Our conversation centered on the possibility that at Pasadena I might continue X-ray work with viruses. Virtually no words went to DNA. When I brought up the X-ray pictures at King's, Linus gave the opinion that very accurate X-ray work of the type done by his associates on amino acids was vital to our eventual understanding of the nucleic acids. I got much further with Ava Helen. Learning that I would be in Cambridge next year, she talked about her son Peter. Already I knew that Peter was accepted by Bragg to work toward a Ph.D. with John Kendrew. This was despite the fact that his Cal Tech grades left much to be desired, even considering his long bout with mononucleosis. John, however, did not want to challenge Linus' desire to place Peter with him, especially knowing that he and his beautiful blonde sister gave smashing parties. Peter and Linda, if she were to visit him, would undoubtedly liven up the Cambridge scene. Then the dream of virtually every Cal Tech chemistry student was that Linda would make his reputation by marrying him. The scuttlebutt about Peter centered on girls and was confused. But now Ava Helen gave me the dope that Peter was an exceptionally fine boy whom everybody would enjoy having around as much as she did. All the same, I remained silently unconvinced that Peter would add as much to our lab as Linda. When Linus beckoned that they must go, I told Ava Helen that I would help her son adjust to the restricted life of the Cambridge research student.
A garden party at Sans Souci, the country home of the Baroness Edmond de Rothschild, effectively brought the meeting to its end. Dressing was no easy matter for me. Just before the biochemical congress all my belongings were snatched from my train compartment as I was sleeping. Except for a few items picked up at an army PX, the clothes I still possessed had been chosen for a subsequent visit to the Italian Alps. While I felt ease giving my talk on TMV in shorts, the French contingent feared that I would go one step further by arriving at Sans Souci in the same outfit. A borrowed jacket and tie, however, made me superficially presentable as our bus driver let us out in front of the huge country house. Sol Spiegelman and I went straight for a butler carrying smoked salmon and champagne, and after a few minutes sensed the value of a cultivated aristocracy. Just before we were to reboard the bus, I wandered into the large drawing room dominated by a Hals and a Rubens. The Baroness was telling several visitors how pleased she was to have such distinguished guests. She did regret, however, that the mad Englishman from Cambridge decided not to come and enliven the mood. For an instant I was puzzled, until I realized that Lwoff had thought it prudent to warn the Baroness about an unclothed guest who might prove eccentric. The message of my first meeting with the aristocracy was clear. I would not be invited back if I acted like everyone else.
 |
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20.
TO FRANCIS' dismay, I showed little tendency to concentrate on DNA when my summer holiday ended. I was preoccupied with sex, but not of a type that needed encouragement. The mating habits of bacteria were admittedly a unique conversation piece absolutely no one in his and Odile's social circle would guess bacteria had sex lives. On the other hand, working out how they did it was best left to minor minds. Rumors of male and female bacteria were floating about at Royaumont, but not until early in September, when I attended a small meeting on microbial genetics at Pallanza, did I get the facts from the horse's mouth. There, Cavalli-Sforza and Bill Hayes talked about the experiments by which they and Joshua Lederberg had just established the existence of two discrete bacterial sexes. Bill's appearance was the sleeper of the three-day gathering: before his talk no one except Cavalli-Sforza knew he existed. As soon as he had finished his unassuming re port, however, everyone in the audience knew that a bombshell had exploded in the world of Joshua Lederberg. In I946 Joshua, then only twenty, burst upon the biological world by announcing that bacteria mated and showed genetic recombination. Since then he had carried out such a prodigious number of pretty experiments that virtually no one except Cavalli dared to work in the same field. Hearing Joshua give Rabelaisian nonstop talks of three to five hours made it all too clear that he was an enfant terrible. Moreover, there was his godlike quality of each year expanding in size, perhaps eventually to fill the universe.
Despite Joshua's fabulous cranium, the genetics of bacteria became messier each year.. Only Joshua took any enjoyment from the rabbinical complexity shrouding his recent papers. Occasionally I would try to plow through one, but inevitably I'd get stuck and put it aside for an other day. No high-power thoughts, however, were required to understand that the discovery of the two sexes might soon make the genetic analysis of bacteria straightforward. Conversations with Cavalli, nonetheless, hinted that Joshua was not yet prepared to think simply. He liked the classical genetic assumption that male and female cells contributed equal amounts of genetic material, even though the resulting analysis was perversely complex. In contrast, Bill's reasoning started from the seemingly arbitrary hypothesis that only a fraction of the male chromosomal material enters the female cell. Given this assumption, further reasoning was infinitely simpler. As soon as I returned to Cambridge, I beelined out to the library containing the journals to which Joshua had sent his recent work. To my delight I made sense of almost all the previously bewildering genetic crosses. A few matings still were inexplicable, but, even so, the vast masses of data now falling into place made me certain that we were on the right track. Particularly pleasing was the possibility that Joshua might be so stuck on his classical way of thinking that I would accomplish the unbelievable feat of beating him to the correct interpretation of his own experiments.
My desire to clean up skeletons in Joshua's closet left Francis almost cold. The discovery that bacteria were divided into male and female sexes amused but did not arouse him. Almost all his summer had been spent collecting pedantic data for his thesis, and now he was in a mood to think about important facts. Frivolously worrying whether bacteria had one, two, or three chromosomes would not help us win the DNA structure. As long as I kept watch on the DNA literature, there was a chance that something might pop out of lunch or teatime conversations. But if I went back to pure biology, the advantage of our small headstart over Linus might suddenly vanish. At this time there was still a nagging feeling in Francis' mind that Chargaff's rules were a real key. In fact, I was away in the Alps he had spent a week trying to prove experimentally that in water solutions there were attractive forces between adenine and thymine, and between guanine and cytosine. But his efforts had yielded nothing. In addition, he was really never at ease talking with Griffith. Somehow their brains didn't jibe well, and there would be long awkward pauses after Francis had thrashed through the merits of a given hypothesis. This was no reason, however, not to tell Maurice that conceivably adenine was attracted to thymine and guanine to cytosine. Since he had to be in London late in October for another reason, he dropped a line to Maurice saying he could come by King's. The reply, inviting him to lunch, was unexpectedly cheerful, and so Francis looked forward to a realistic discussion of DNA.
However, he made the mistake of tactfully appearing not too interested in DNA by starting to talk about proteins. Over half the lunch was thus wasted when Maurice changed the topic to Rosy and droned on and on about her lack of cooperation. Meantime, Francis' mind fastened on a more amusing topic until, the meal over he remembered that he had to rush to a 2:30 appointment. Hurriedly he left the building and was out on the street before realizing he had not brought up the agreement between Griffith's calculations and Chargaff's data. Since it would look too silly to rush back in, he went on, returning that evening to Cambridge. The following morning, after I was told about the futility of the lunch, Francis tried to generate enthusiasm for our having a second go at the structure. Another zeroing in on DNA, however, did not make sense to me. No fresh facts had come in to chase away the stale taste of last winter's debacle. The only new result we were likely to pick up before Christmas was the divalent metal content of the DNA containing phage T4. A high value, if found, would strongly suggest binding of Mg++ to DNA. With such evidence I might at last force the King's groups to analyze their DNA samples. But the prospects for immediate hard results were not good. First, Maaløe's colleague Nils Jeme must send the phage from Copenhagen. Then I would need to arrange for accurate measurement of both the divalent metals and the DNA content. Finality, Rosy would have to budge.
Fortunately, Linus did not look like an immediate threat on the DNA front. Peter Pauling arrived with the inside news that his father was preoccupied with schemes for the? supercoiling of α-helix in the hair protein, keratin. This was not especially good news to Francis. For almost a year he had been in and out of euphoric moods about how α-helices packed together in coiled coils. The trouble was that his mathematics never gelled tightly. When pressed he admitted that his argument had a wolly component. Now he faced the possibility that Linus' solution would be no better and yet he would get all the credit for the coiled coils. Experimental work for his thesis was broken off so that the coiled-coil equations could be taken up with redoubled effort. This time the correct equations fell out, partly thanks to the help of Kreisel, who had come over to Cambridge to spend a weekend with Francis. A letter to Nature was quickly drafted and given to Bragg to send on to the editors, with a covering note asking for speedy publication. If the editors were told that a British article was of above average interest, they would try to publish the manuscript almost immediately. With luck, Francis' coiled coils would get into print as soon as if not before Pauling's.
Thus there was growing acceptance both in and outside Cambridge that Francis' brain was a genuine asset. Though a few dissidents still thought he was a laughing talking-machine, he nonetheless saw problems through to the finish line. A reflection of his increasing stature was an offer received early in the fall to join David Harker in Brooklyn for a year. Harker, having collected a million dollars to solve the structure of the enzyme ribonuclease, was in search of talent, and the offer of six thousand for one year seemed to Odile wonderfully generous. As expected, Francis had mixed feelings. There must be reasons why there were so many jokes about Brooklyn. On the other hand, he had never been in the States, and even Brooklyn would provide a base from which he could visit more agreeable regions. Also, if Bragg knew that Crick would be away for a year, he might view more favorably, a request from Max and John that Francis be reappointed for another three years after his thesis was submitted. The best course seemed tentatively to accept the offer, and in mid-October he wrote Harker that he would come to Brooklyn in the fall of the following year.
As the fall progressed, I remained ensnared by bacterial matings, often going up to London to talk with Bill Hayes at his Hammersmith Hospital lab. My mind snapped back to DNA on the evenings when I managed to catch Maurice for dinner on my way home to Cambridge. Some afternoons, however, he would quietly slip away, and his lab group had it that a special girl friend existed. Finally it came out that everything was above board. The afternoons were spent at a gymnasium learning how to fence. The situation with Rosy remained as sticky as ever. Upon his return from Brazil, the unmistakable impression was given that she considered collaboration even more impossible than before. Thus, for relief, Maurice had taken up interference microscopy to find a trick for weighing chromosomes. The question of finding Rosy a job elsewhere had been brought to his boss, Randall, but the best to be hoped for would be a new position starting a year hence. Sacking her immediately on the basis of her acid smile just couldn't be done. Moreover, her X-ray pictures were getting prettier and prettier. She gave no sign, however, of liking helices any better. In addition, she thought there was evidence that the sugar-phosphate backbone was on the outside of the molecule. There was no easy way to judge whether this assertion had any scientific basis. As long as Francis and I remained closed out from the experimental data, the best course was to maintain an open mind. So I returned to my thoughts about sex.
 |
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21.
I WAS by now living in Clare College. Soon after my arrival at the Cavendish, Max had slipped me into Clare as a research student. Working for another Ph.D. was nonsense, but only by using this dodge would I have the possibility of college rooms. Clare was an unexpectedly happy choice. Not only was it on the Cam with a perfect garden but, as I was to learn later, it was especially considerate toward Americans. Before this happened I was almost stuck in Jesus. At (short notice Max and John thought I would have the best chance to be accepted by one of the small colleges, since they had relatively fewer research students than the large, more prestigious, and wealthy colleges like Trinity or King's. Max thus asked the physicist Denis Wilkinson, (then a Fellow of Jesus, whether an opening might exist in his college. The following day Denis came by to say Jesus would have me and that I should arrange an appointment to learn the formalities of matriculation.
A talk with its head tutor, however, made me try elsewhere. Jesus' possession of only a few research students appeared related to its formidable reputation on the river. No research student could live in, and so the only predictable consequences of being a Jesus man were bills for a Ph.D. that I would never acquire. Nick Hammond, the classicist head tutor at Clare, painted a much rosier outlook for their foreign research students. In my second year up, I could move into the college. Moreover, at Clare there would be several American research students I might meet. Nonetheless, during my first Cambridge year, when I lived on Tennis Court Road with the Kendrews, I saw virtually nothing of college life. After matriculation I went into hall for several meals until I discovered that I was unlikely to meet anyone during the ten-to-twelve-minute interval needed to slop down the brown soup, stringy meat, and heavy pudding provided on most evenings. Even during my second Cambridge year, when I moved into rooms on the R staircase of Clare's Memorial Court, my boycott of college food continued. Breakfast at the Whim could occur much later than if I went to hall. For 3/6 the whim gave a half-warm site to read The Times while flatcapped Trinity types turned the pages of the Telegraph or News Chronicle. Finding suitable evening food on the town was trickier. Eating at the Artsor the Bath Hotel was reserved for special occasions, so when Odile or Elizabeth Kendrew did not invite me to supper I took in the poison put out by the local Indian and Cypriote establishments.
My stomach lasted only until early November before violent pains hit me almost every evening. Alternative treatments with baking soda and mi1k did not help, and so, despite Elizabeth's assurance that nothing was wrong, I showed up at the ice-cold Trinity Street surgery of a local doctor. After I was allowed to appreciate the oars on his walls, I was expelled with a prescription for a large bottle of white fluid to be taken after meals. This kept me going for almost two weeks, when, with the bottle empty, I returned to the surgery with the fear that I had an ulcer. The news that an alien's dyspeptic pains were persisting ~did not, however, evoke any sympathetic words, and again I retreated into Trinity Street with a prescription for more white stiff.
That evening I stopped by at the Cricks' newly bought house, hoping that gossip with Odile would make me forget my stomach. The Green Door recently had been abandoned for larger quarters on nearby Portugal Place. Already the dreary wallpaper on the lower floors was gone, and Odile was busy making curtains appropriate for a house large enough to have a bathroom. After I was given a glass of warm milk we began discussing Peter Pauling's discovery of Nina, Max's young Danish au pair ~girl. Then the problem was taken up of how I might establish a connection with the high-class boarding house run by Camille "Pop" Prior at Scroope Terrace. The food at Pop's would offer no improvement over hall, but the French girls who came to Cambridge to improve their English were another matter. A seat at Pop's dinner table, however, could not be asked for directly. Instead, both Odile and Francis thought the best tactic for getting a foot in the door was to commence French lessons with Pop, whose deceased husband had been the Professor of French before the war. If I suited Pop's fancy, I might be invited to one of her sherry parties and meet her current crop of foreign girls. Odile promised to ring Pop to see if lessons could be arranged, and I cycled back to college with the hope that soon my stomach pains would have reason to vanish.
Back in my rooms I lit the coal fire, knowing there was no chance that the sight of my breath would disappear before I was ready for bed. With my fingers too cold to write legibly I hudd1ed next to the fireplace, daydreaming about how several DNA chains could fold together in a pretty and hopefully scientific way. Soon, however, I abandoned thinking at the molecular level and turned to the much easier job of reading biochemical papers on the interrelations of DNA, RNA, and protein synthesis. Virtually all the evidence then available made me believe that DNA was the template upon which RNA chains were made. In turn, RNA chains were the likely candidates for the templates for protein synthesis. There (were some fuzzy data using sea urchins, interpreted as a transformation of DNA into RNA, but I preferred to trust other experiments showing that DNA molecules, once synthesized, are very very stable. The idea of the genes' being immortal smelled right, and so on the wall above my desk I taped up a paper sheet saying DNA →.RNA ~→ protein. The arrows did not signify chemical transformations, but instead expressed the transfer of genetic information from the sequences of nucleotides in DNA molecules to the sequences of amino acids in proteins.
Though I fell asleep contented with the thought that I understood the relationship between nucleic acids and protein synthesis, the chill of dressing in an ice-cold bedroom brought me back to the knowing truth that a slogan was no substitute for the DNA structure. Without it, the only impact that Francis and I were likely to have was to convince the biochemists we met in a nearby pub that we would never appreciate the fundamental significance of complexity in biology. What was worse, even when Francis stopped thinking about coiled coils or I about bacterial genetics, we still remained stuck at the same place were twelve months before. Lunches at the Eagle frequent1y went by without a mention of DNA, though usually somewhere on our after-lunch walk along the backs genes would creep in for a moment. On a few walks our enthusiasm would build up to the point that we fiddled with the models when we got back to our office. But almost immediately Francis saw that the reasoning which had momentarily given us hope led nowhere. Then he would go back to the examination of the hemoglobin X-ray photographs out of which his thesis must emerge. Several times I carried on alone for a half hour or so, but without Francis' reassuring chatter my in-ability to think in three dimensions became all too apparent.
A talk with its head tutor, however, made me try elsewhere. Jesus' possession of only a few research students appeared related to its formidable reputation on the river. No research student could live in, and so the only predictable consequences of being a Jesus man were bills for a Ph.D. that I would never acquire. Nick Hammond, the classicist head tutor at Clare, painted a much rosier outlook for their foreign research students. In my second year up, I could move into the college. Moreover, at Clare there would be several American research students I might meet. Nonetheless, during my first Cambridge year, when I lived on Tennis Court Road with the Kendrews, I saw virtually nothing of college life. After matriculation I went into hall for several meals until I discovered that I was unlikely to meet anyone during the ten-to-twelve-minute interval needed to slop down the brown soup, stringy meat, and heavy pudding provided on most evenings. Even during my second Cambridge year, when I moved into rooms on the R staircase of Clare's Memorial Court, my boycott of college food continued. Breakfast at the Whim could occur much later than if I went to hall. For 3/6 the whim gave a half-warm site to read The Times while flatcapped Trinity types turned the pages of the Telegraph or News Chronicle. Finding suitable evening food on the town was trickier. Eating at the Artsor the Bath Hotel was reserved for special occasions, so when Odile or Elizabeth Kendrew did not invite me to supper I took in the poison put out by the local Indian and Cypriote establishments.
My stomach lasted only until early November before violent pains hit me almost every evening. Alternative treatments with baking soda and mi1k did not help, and so, despite Elizabeth's assurance that nothing was wrong, I showed up at the ice-cold Trinity Street surgery of a local doctor. After I was allowed to appreciate the oars on his walls, I was expelled with a prescription for a large bottle of white fluid to be taken after meals. This kept me going for almost two weeks, when, with the bottle empty, I returned to the surgery with the fear that I had an ulcer. The news that an alien's dyspeptic pains were persisting ~did not, however, evoke any sympathetic words, and again I retreated into Trinity Street with a prescription for more white stiff.
That evening I stopped by at the Cricks' newly bought house, hoping that gossip with Odile would make me forget my stomach. The Green Door recently had been abandoned for larger quarters on nearby Portugal Place. Already the dreary wallpaper on the lower floors was gone, and Odile was busy making curtains appropriate for a house large enough to have a bathroom. After I was given a glass of warm milk we began discussing Peter Pauling's discovery of Nina, Max's young Danish au pair ~girl. Then the problem was taken up of how I might establish a connection with the high-class boarding house run by Camille "Pop" Prior at Scroope Terrace. The food at Pop's would offer no improvement over hall, but the French girls who came to Cambridge to improve their English were another matter. A seat at Pop's dinner table, however, could not be asked for directly. Instead, both Odile and Francis thought the best tactic for getting a foot in the door was to commence French lessons with Pop, whose deceased husband had been the Professor of French before the war. If I suited Pop's fancy, I might be invited to one of her sherry parties and meet her current crop of foreign girls. Odile promised to ring Pop to see if lessons could be arranged, and I cycled back to college with the hope that soon my stomach pains would have reason to vanish.
Back in my rooms I lit the coal fire, knowing there was no chance that the sight of my breath would disappear before I was ready for bed. With my fingers too cold to write legibly I hudd1ed next to the fireplace, daydreaming about how several DNA chains could fold together in a pretty and hopefully scientific way. Soon, however, I abandoned thinking at the molecular level and turned to the much easier job of reading biochemical papers on the interrelations of DNA, RNA, and protein synthesis. Virtually all the evidence then available made me believe that DNA was the template upon which RNA chains were made. In turn, RNA chains were the likely candidates for the templates for protein synthesis. There (were some fuzzy data using sea urchins, interpreted as a transformation of DNA into RNA, but I preferred to trust other experiments showing that DNA molecules, once synthesized, are very very stable. The idea of the genes' being immortal smelled right, and so on the wall above my desk I taped up a paper sheet saying DNA →.RNA ~→ protein. The arrows did not signify chemical transformations, but instead expressed the transfer of genetic information from the sequences of nucleotides in DNA molecules to the sequences of amino acids in proteins.
Though I fell asleep contented with the thought that I understood the relationship between nucleic acids and protein synthesis, the chill of dressing in an ice-cold bedroom brought me back to the knowing truth that a slogan was no substitute for the DNA structure. Without it, the only impact that Francis and I were likely to have was to convince the biochemists we met in a nearby pub that we would never appreciate the fundamental significance of complexity in biology. What was worse, even when Francis stopped thinking about coiled coils or I about bacterial genetics, we still remained stuck at the same place were twelve months before. Lunches at the Eagle frequent1y went by without a mention of DNA, though usually somewhere on our after-lunch walk along the backs genes would creep in for a moment. On a few walks our enthusiasm would build up to the point that we fiddled with the models when we got back to our office. But almost immediately Francis saw that the reasoning which had momentarily given us hope led nowhere. Then he would go back to the examination of the hemoglobin X-ray photographs out of which his thesis must emerge. Several times I carried on alone for a half hour or so, but without Francis' reassuring chatter my in-ability to think in three dimensions became all too apparent.
I was thus not at all displeased that we were sharing our office with Peter Pauling, then living in the Peterhouse hostel as a research student of John Kendrew's. Peter's presence meant that, whenever more science was pointless, the conversation could dwell on the comparative virtues of girls from England, the Continent, and California. A fetching face, however, had nothing to do with the broad grin on Peter's face when he sauntered into the office one afternoon in the middle of December and put his feet up on his desk. In his hand was a letter from the States that he had picked up on his return to Peterhouse for lunch. It was from his father. In addition to routine family gossip was the long-feared news that Linus now had a structure for DNA. No details were given of what he was up to, and so each time the letter passed between Francis and me the greater was our frustration. Francis then began pacing up and down the room thinking aloud, hoping that in a great intellectual fervor he could reconstruct what Linus might have done. As long as Linus had not told us the answer, we should get equal credit if we announced it at the same time. Nothing worthwhile had emerged, though, by the time he walked upstairs to tea and told Max and John of the letter. Bragg was in for a moment, but neither of us wanted the perverse joy of informing him that the English labs were again about to be humiliated by the Americans. As we munched chocolate biscuits, John tried to cheer us up with the possibility of Linus' being wrong. After all, he had never seen Maurice's and Rosy's pictures. Our hearts, however, told us otherwise.
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22.
NO FURTHER news emerged from Pasadena before Christmas. Our spirits slowly went up, for if Pauling had found a really exciting answer the secret could not be kept long. One of his graduate students must certainly know what his model looked like, and if there were obvious biological implications the rumor would have quick1y reached us. Even if Linus was somewhere near the right structure, the odds seemed against his getting near the secret of gene replication. Also, the more we thought about DNA chemistry, the more unlikely seemed the possibility that even Linus could pick off the structure in total ignorance of the work at King's. Maurice was told that Pauling was in his pasture when I passed through London on my way to Switzerland for a Christmas skiing holiday. I was hoping that the urgency created by Linus' assault on DNA might make him ask Francis and me for help. However, if Maurice thought that Linus had a chance to steal the prize, he didn't let on. Much more important was the news that Rosy's days at King's were numbered. She had told Maurice that she wanted soon to transfer to Bemal's lab at Birkbeck College. Moreover, to Maurice's surprise and relief, she would not take the DNA problem with her. In the next several months she was to conclude her stay by writing up her work for publication. Then, with Rosy at last out of his life, he would commence an all-out search for the structure.
Upon my return to Cambridge in mid-January, I sought out Peter to learn what was in his recent letters from home. Except for one brief reference to DNA, all the news was family gossip. The one pertinent item, however, was not reassuring. A manuscript on DNA had been written, a copy of which would soon be sent to Peter. Again there was not a hint of what the model looked like. While waiting for the manuscript to arrive, I kept my nerves in check by writing up my ideas on bacterial sexuality. A quick visit to Cavalli in Milan, which occurred just after my skiing holiday in Zennatt, had convinced me that my speculations about how bacteria mated were likely to be right. Since I was afraid that Lederberg might soon see the same light, I was anxious to publish quickly a joint article with Bill Hayes. But this manuscript was not in final form when, in the first week of February, the Pauling paper crossed the Atlantic.
Two copies, in fact, were dispatched to Cambridge – one to Sir Lawrence, the other to Peter. Bragg's response upon receiving it was to put it aside. Not knowing that Peter would also get a copy, he hesitated to take the manuscript down to Max's office. There Francis would see it and set off on another wild-goose chase. Under the present timetable there were only eight months more of Francis' laugh to bear. That is, if his thesis was finished on schedule. Then for a year, if not more, with ~Crick in exile in Brooklyn, peace and serenity would prevail. While Sir Lawrence was pondering whether to chance taking Crick's mind off his thesis, Francis and I were poring over the copy that Peter brought in after lunch. Peter's face betrayed something important as he entered the door, and my stomach sank in apprehension at learning that all was lost. Seeing that neither Francis nor I could bear any further suspense, he quickly told us that the model was a three-chain helix with the sugar-phosphate backbone in the center. This sounded so suspiciously like our aborted effort of last year that immediately I wondered whether we might already have had the credit and glory of a great discovery if Bragg had not held us back. Giving Francis no chance to ask for the manuscript, I pulled it out of Peter's outside coat pocket and began reading. By spending less than a minute with the summary and the introduction, I was soon at the figures showing the locations of the essential atoms.
At once I felt something was not right. I could not pinpoint the mistake, however, until I looked at the illustrations for several minutes. Then I realized that the phosphate groups in Linus' model were not ionized, but that each group contained a bound hydrogen atom and so had no net charge. Pauling's nucleic acid in a sense was not an acid at all. Moreover, the uncharged phosphate groups were not incidental features. The hydrogens were part of the hydrogen bonds that held together the three intertwined chains. Without the hydrogen atoms, the chains would immediately fly apart and the structure vanish. Everything I knew about nucleic-acid chemistry indicated that phosphate groups never contained bound hydrogen atoms. No one had ever questioned that DNA was a moderately strong acid. Thus, under physiological conditions, there would always be positively charged ions like sodium or magnesium lying nearby to neutralize the negatively charged phosphate groups. All our speculations about whether divalent ions held the chains together would have made no sense if there were hydrogen atoms firmly bound to the phosphates. Yet somehow Linus, unquestionably the world's most astute chemist, had come to the opposite conclusion.
When Francis was amazed equally by Pauling's unorthodox chemistry, I began to breathe slower. By then I knew we were still in the game. Neither of us, however, had the slightest clue to the steps that had led Linus to his blunder. If a student had made a similar mistake, he would be thought unfit to benefit from Cal Tech's chemistry faculty. Thus, we could not but initially worry whether Linus' model followed from a revolutionary re-evaluation of the acid-base properties of very large molecules. The tone of the manuscript, however, argued against any such advance in chemical theory. No reason existed to keep secret a first-rate theoretical break-through. Rather, if that had occurred Linus would have written two papers, the first describing his new theory, the second showing how it was used to solve the DNA structure. The blooper was too unbelievable to keep secret for more than a few minutes. I dashed over to Roy Markham's lab to spurt out the news and to receive further reassurance that Linus' chemistry was screwy. Markham predictably expressed pleasure that a giant had forgotten elementary college chemistry. He then could not refrain from revealing how one of Cambridge's great men had on occasion also forgotten his chemistry. Next I hopped over to the organic chemists't where again I heard the soothing words that DNA was an acid...
By teatime I was back in the Cavendish, where Francis was explaining to John and Max that no further time must be lost on this side of the Atlantic. When his mistake became known, Linus would not stop until he had captured the right structure. Now our immediate hope was that his chemical colleagues would be more than ever awed by his intellect and not probe the details of his model. But since the manuscript had already been dispatched to the Proceedings of the National Academy, by mid-March at the latest Linus' paper would be spread around the world. Then it would be only a matter of days before the error would be discovered. We had anywhere up to six weeks before Linus again was in full-time pursuit of DNA.
Though Maurice had to be warned, we did not immediately ring him. The pace of Francis' words might cause Maurice to find a reason for terminating the conversation before all the implications of Pauling's folly could be hammered home. Since in several days I was to go up to London to see Bill Hayes, the sensible course was to bring the manuscript with me for Maurice's and Rosy's inspection. Then, as the stimulation of the last several hours had made further work that day impossible, Francis and I went over to the Eagle. The moment its doors opened for the evening we were there to drink a toast to the Pauling failure. Instead of sherry, I let Francis buy me a whiskey. Though the odds still appeared against us, Linus had not yet won his Nobel.
Upon my return to Cambridge in mid-January, I sought out Peter to learn what was in his recent letters from home. Except for one brief reference to DNA, all the news was family gossip. The one pertinent item, however, was not reassuring. A manuscript on DNA had been written, a copy of which would soon be sent to Peter. Again there was not a hint of what the model looked like. While waiting for the manuscript to arrive, I kept my nerves in check by writing up my ideas on bacterial sexuality. A quick visit to Cavalli in Milan, which occurred just after my skiing holiday in Zennatt, had convinced me that my speculations about how bacteria mated were likely to be right. Since I was afraid that Lederberg might soon see the same light, I was anxious to publish quickly a joint article with Bill Hayes. But this manuscript was not in final form when, in the first week of February, the Pauling paper crossed the Atlantic.
Two copies, in fact, were dispatched to Cambridge – one to Sir Lawrence, the other to Peter. Bragg's response upon receiving it was to put it aside. Not knowing that Peter would also get a copy, he hesitated to take the manuscript down to Max's office. There Francis would see it and set off on another wild-goose chase. Under the present timetable there were only eight months more of Francis' laugh to bear. That is, if his thesis was finished on schedule. Then for a year, if not more, with ~Crick in exile in Brooklyn, peace and serenity would prevail. While Sir Lawrence was pondering whether to chance taking Crick's mind off his thesis, Francis and I were poring over the copy that Peter brought in after lunch. Peter's face betrayed something important as he entered the door, and my stomach sank in apprehension at learning that all was lost. Seeing that neither Francis nor I could bear any further suspense, he quickly told us that the model was a three-chain helix with the sugar-phosphate backbone in the center. This sounded so suspiciously like our aborted effort of last year that immediately I wondered whether we might already have had the credit and glory of a great discovery if Bragg had not held us back. Giving Francis no chance to ask for the manuscript, I pulled it out of Peter's outside coat pocket and began reading. By spending less than a minute with the summary and the introduction, I was soon at the figures showing the locations of the essential atoms.
At once I felt something was not right. I could not pinpoint the mistake, however, until I looked at the illustrations for several minutes. Then I realized that the phosphate groups in Linus' model were not ionized, but that each group contained a bound hydrogen atom and so had no net charge. Pauling's nucleic acid in a sense was not an acid at all. Moreover, the uncharged phosphate groups were not incidental features. The hydrogens were part of the hydrogen bonds that held together the three intertwined chains. Without the hydrogen atoms, the chains would immediately fly apart and the structure vanish. Everything I knew about nucleic-acid chemistry indicated that phosphate groups never contained bound hydrogen atoms. No one had ever questioned that DNA was a moderately strong acid. Thus, under physiological conditions, there would always be positively charged ions like sodium or magnesium lying nearby to neutralize the negatively charged phosphate groups. All our speculations about whether divalent ions held the chains together would have made no sense if there were hydrogen atoms firmly bound to the phosphates. Yet somehow Linus, unquestionably the world's most astute chemist, had come to the opposite conclusion.
When Francis was amazed equally by Pauling's unorthodox chemistry, I began to breathe slower. By then I knew we were still in the game. Neither of us, however, had the slightest clue to the steps that had led Linus to his blunder. If a student had made a similar mistake, he would be thought unfit to benefit from Cal Tech's chemistry faculty. Thus, we could not but initially worry whether Linus' model followed from a revolutionary re-evaluation of the acid-base properties of very large molecules. The tone of the manuscript, however, argued against any such advance in chemical theory. No reason existed to keep secret a first-rate theoretical break-through. Rather, if that had occurred Linus would have written two papers, the first describing his new theory, the second showing how it was used to solve the DNA structure. The blooper was too unbelievable to keep secret for more than a few minutes. I dashed over to Roy Markham's lab to spurt out the news and to receive further reassurance that Linus' chemistry was screwy. Markham predictably expressed pleasure that a giant had forgotten elementary college chemistry. He then could not refrain from revealing how one of Cambridge's great men had on occasion also forgotten his chemistry. Next I hopped over to the organic chemists't where again I heard the soothing words that DNA was an acid...
By teatime I was back in the Cavendish, where Francis was explaining to John and Max that no further time must be lost on this side of the Atlantic. When his mistake became known, Linus would not stop until he had captured the right structure. Now our immediate hope was that his chemical colleagues would be more than ever awed by his intellect and not probe the details of his model. But since the manuscript had already been dispatched to the Proceedings of the National Academy, by mid-March at the latest Linus' paper would be spread around the world. Then it would be only a matter of days before the error would be discovered. We had anywhere up to six weeks before Linus again was in full-time pursuit of DNA.
Though Maurice had to be warned, we did not immediately ring him. The pace of Francis' words might cause Maurice to find a reason for terminating the conversation before all the implications of Pauling's folly could be hammered home. Since in several days I was to go up to London to see Bill Hayes, the sensible course was to bring the manuscript with me for Maurice's and Rosy's inspection. Then, as the stimulation of the last several hours had made further work that day impossible, Francis and I went over to the Eagle. The moment its doors opened for the evening we were there to drink a toast to the Pauling failure. Instead of sherry, I let Francis buy me a whiskey. Though the odds still appeared against us, Linus had not yet won his Nobel.
 |
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23.
MAURICE was busy when, just before four, I walked in with the news that the Pauling model was far off base. so I went down the corridor to Rosy's lab, hoping she would be about. Since the door was already open, I pushed it open to see her bending over a lighted box upon which lay an X-ray photograph she was measuring. Momentarily startled by my entry, she quickly regained her composure and, looking straight at my face, let her eyes tell me that uninvited guests should have the courtesy to knock. I started to say that Maurice was busy, but before the insult was out I asked her whether she wanted to look at Peter's copy of his father's manuscript. Though I was curious how long she would take to spot the error, Rosy was not about to play games with me. I immediately explained where Linus had gone astray. In doing so, I could not refrain from pointing out the superficial resemblance between Pauling's three-chain helix and the model that Francis and I. had shown her fifteen months earlier. The fact that Pauling's deductions about symmetry were no more inspired than our awkward efforts of the year before would, I thought, amuse her. The result was just the opposite. Instead, she became increasingly annoyed with my recurring references to helical structures. Coolly she pointed out that not a shred of evidence permitted Linus, or anyone else, to postulate a helical structure for DNA. Most of my words to her were superfluous, for she knew that Pauling was wrong the moment I mentioned a helix.
Interrupting her harangue, I asserted that the simplest form for any regular polymeric molecule was a helix. Knowing that she might counter with the fact that the sequence ' of bases was unlikely to be regular, I went on with the argument that, since DNA molecules form crystals, the nucleotide order must not affect the general structure. Rosy by then was hardly able to control her temper, and her voice rose as she told me that the stupidity of my remarks would be obvious if I would stop blubbering and look at her X-ray evidence. I was more aware of her data than she realized. Several months earlier Maurice had told me the nature of her so-called antihelical results. Since Francis had assured me that they were a red herring, I decided to risk a full explosion. Without further hesitation I implied that she was incompetent in interpreting X-ray pictures. If only she would learn some theory, she would understand how her supposed antihelical features arose from the minor distortions needed to pack regular helices into a crystalline lattice.
Suddenly Rosy came from behind the lab bench that separated us and began moving toward me. Fearing that in her hot anger she might strike me, I grabbed up the Pauling manuscript and hastily retreated to the open door. My escape was blocked by Maurice, who, searching for me, had just then stuck his head through. While Maurice and Rosy looked at each other over my slouching figure, I lamely told Maurice that the conversation between Rosy and me was over and that I had been about to look for him in the tea room. Simultaneously I was, inching my body from between them, leaving Maurice face to face with Rosy. Then, when Maurice failed to disengage himself immediately, I feared that out of polite- j ness he would ask Rosy to join us for tea. Rosy, however, removed Maurice from his uncertainty by turning around and firmly shutting the door. Walking down the passage, I told Maurice how his unexpected appearance might have prevented Rosy from assaulting me. Slowly he assured me that this very well might have happened. Some months earlier she had made a similar lunge toward him. They had almost come to blows following an argument in his room. When he wanted to escape, Rosy had blocked the door and had moved out of the way only at the last moment. But then no third person was on hand.
My encounter with Rosy opened up Maurice to a degree that I had not seen before. Now that I need no longer merely imagine the emotional hell he had faced during the past two years, he could treat me almost as a fellow collaborator rather than as a distant acquaintance with whom close confidences inevitably led to painful misunderstandings. To my surprise, he revealed that with the help of his assistant Wilson he had quietly been duplicating some of Rosy's and Gosling's X-ray work. Thus there need not be a large time gap before Maurice's research efforts were in full swing. Then the even more important cat was let out of the bag: since the middle of the summer Rosy had had evidence for a new three-dimensional form of DNA. It occurred when the DNA molecules were surrounded by a large amount of water. When I asked what the pattern was like, Maurice went into the adjacent room to pick up a print of the new form they called the "B" structure.
The instant I saw the picture my mouth fell open and my pulse began to race. The pattern was unbelievably simpler than those obtained previously ("A" form). Moreover, the black cross of reflections which dominated the picture could arise only from a helical structure. With the A form, the argument for a helix was never straightforward and considerable ambiguity existed as to exactly which type of helical symmetry was present. With the B form, however, mere inspection of its Xray picture gave several of the vital helica1 parameters. Conceivably, after only a few minutes' calculations, the number of chains in the molecule could be fixed. Pressing Maurice for what they had done using the B photo, I learned that his colleague R. D. B. Fraser earlier had been doing some serious playing with three-chain models but that so far nothing exciting had come up. Though Maurice conceded that the evidence for a helix was now overwhelming-the Stokes-Cochran-Crick theory clearly indicated that a helix must exist-this was not to him of major significance. After all, he had previously thought a helix would emerge. The real problem was the absence of any structural hypothesis which would allow them to pack the bases regularly in the inside of the helix. Of course this presumed that Rosy had hit it right in wanting the bases in the center and the backbone outside. Though Maurice told me he was now quite convinced she was correct, I remained skeptical, for her evidence was still out of the reach of Francis and me.
On our way to Soho for supper I returned to the problem of Linus, emphasizing that smiling too long over his mistake might be fatal. The position would be far safer if Pauling had been merely wrong instead of looking like a fool. Soon, if not already, he would be at it day and night. There was the further danger that if he put one of his assistants to taking DNA photographs, the B structure would also be discovered in Pasadena. Then, in a week at most, Linus would have the structure. Maurice refused to get excited. My repeated refrain that DNA could fall at any moment sounded too suspiciously like Francis in one of his overwrought periods. For years Francis had been trying to tell him what was important, but the more dispassionately he considered his life, the more he knew he had been wise to follow up his own hunches. As the waiter peered over his shoulder, hoping we would finally order, Maurice made sure I understood that if we could all agree where science was going, everything would be solved and we would have no recourse but to be engineers or doctors.
My encounter with Rosy opened up Maurice to a degree that I had not seen before. Now that I need no longer merely imagine the emotional hell he had faced during the past two years, he could treat me almost as a fellow collaborator rather than as a distant acquaintance with whom close confidences inevitably led to painful misunderstandings. To my surprise, he revealed that with the help of his assistant Wilson he had quietly been duplicating some of Rosy's and Gosling's X-ray work. Thus there need not be a large time gap before Maurice's research efforts were in full swing. Then the even more important cat was let out of the bag: since the middle of the summer Rosy had had evidence for a new three-dimensional form of DNA. It occurred when the DNA molecules were surrounded by a large amount of water. When I asked what the pattern was like, Maurice went into the adjacent room to pick up a print of the new form they called the "B" structure.
The instant I saw the picture my mouth fell open and my pulse began to race. The pattern was unbelievably simpler than those obtained previously ("A" form). Moreover, the black cross of reflections which dominated the picture could arise only from a helical structure. With the A form, the argument for a helix was never straightforward and considerable ambiguity existed as to exactly which type of helical symmetry was present. With the B form, however, mere inspection of its Xray picture gave several of the vital helica1 parameters. Conceivably, after only a few minutes' calculations, the number of chains in the molecule could be fixed. Pressing Maurice for what they had done using the B photo, I learned that his colleague R. D. B. Fraser earlier had been doing some serious playing with three-chain models but that so far nothing exciting had come up. Though Maurice conceded that the evidence for a helix was now overwhelming-the Stokes-Cochran-Crick theory clearly indicated that a helix must exist-this was not to him of major significance. After all, he had previously thought a helix would emerge. The real problem was the absence of any structural hypothesis which would allow them to pack the bases regularly in the inside of the helix. Of course this presumed that Rosy had hit it right in wanting the bases in the center and the backbone outside. Though Maurice told me he was now quite convinced she was correct, I remained skeptical, for her evidence was still out of the reach of Francis and me.
On our way to Soho for supper I returned to the problem of Linus, emphasizing that smiling too long over his mistake might be fatal. The position would be far safer if Pauling had been merely wrong instead of looking like a fool. Soon, if not already, he would be at it day and night. There was the further danger that if he put one of his assistants to taking DNA photographs, the B structure would also be discovered in Pasadena. Then, in a week at most, Linus would have the structure. Maurice refused to get excited. My repeated refrain that DNA could fall at any moment sounded too suspiciously like Francis in one of his overwrought periods. For years Francis had been trying to tell him what was important, but the more dispassionately he considered his life, the more he knew he had been wise to follow up his own hunches. As the waiter peered over his shoulder, hoping we would finally order, Maurice made sure I understood that if we could all agree where science was going, everything would be solved and we would have no recourse but to be engineers or doctors.
With the food on the table I tried to fix our thoughts on the chain number, arguing that measuring the location of the innermost reflection on the first and second layer lines might immediately set us on the right track. But since Maurice's long-drawn-out reply never came to the point, I could not decide whether he was saying that no one at King's had measured the pertinent reflections or whether he wanted to eat his meal before it got cold. Reluctantly I ate, hoping that after coffee I might get more, details if I walked him back to his flat. Our bottle of, Chablis, however, diminished my desire for hard facts, and as we walked out of Soho and across Oxford Street, Maurice spoke only of his plans to get a less gloomy apartment in a quieter area. Afterwards, in the cold, almost unheated train compartment, I sketched on the blank edge of my newspaper what I remembered of the B pattern. Then as the train jerked toward Cambridge, I tried to decide between two- and three-chain models. As far as I could tell, the reason the King's group did not like two chains was not foolproof. It depended upon the water content of the DNA samples, a value they admitted might be in great error. Thus by the time I had cycled back to college and climbed over the back gate, I had decided to build two-chain models. Francis would have to agree. Even though he was a physicist, he knew that important biological objects come in pairs.
 |
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24.
BRAGG was in Max's office when I rushed in the next day to blurt out what I had learned. Francis was not yet in, for it was a Saturday morning and he was still home in bed glancing at the Nature that had come in the morning mail. Quickly I started to run through the details of the B form, making a rough sketch to show the evidence that DNA was a helix which repeated its pattern every 34 Å along the helical axis. Bragg soon interrupted me with a question, and I knew my argument had got across. I thus wasted no time in bringing up the problem of Linus, giving the opinion that he was far too dangerous to be allowed a second crack at DNA while the people on this side of the Atlantic sat on their hands. After saying that I was going to ask a Cavendish machinist to make models of the purines and pyrimidines, I remained silent, waiting for Bragg's thoughts to congeal. To my relief, Sir Lawrence not only made no objection but encouraged me to get on with the job of building models. He clearly was not in sympathy with the internal squabbling at King's ─ especially when it might allow Linus, of all people, to get the thrill of discovering the structure of still another important molecule. Also aiding our cause was my work on tobacco mosaic virus. It had given Bragg the impression that I was on my own. Thus he could fall asleep that night untroubled by the nightmare that he had given Crick carte blanche for another foray into frenzied inconsiderateness. I then dashed down the stairs to the machine shop to warn them that I was about to draw up plans for models wanted within a week. Shortly after I was back in our office, Francis strolled in to report that their last night's dinner party was a smashing success. Odile was positively enchanted with the French boy that my sister had brought a1ong. A month previously Elizabeth had arrived for an indefinite stay on her way back to the States. Luckily I could both install her in Camille Prior's boarding house and arrange to take my evening meals there with Pop and her foreign girls. Thus in one blow Elizabeth had been saved from typical English digs, while I looked forward to a lessening of my, stomach pains.
Also living at Pop's was Bertrand Fourcade, the most beautiful male, if not person, in Cambridge. Bertrand, then visiting for a few months to perfect his English, was not unconscious of his unusual beauty and so welcomed the companionship of a girl whose dress was not in shocking contrast with his well-cut clothes. As soon as I had mentioned that we knew the handsome foreigner, Odile expressed delight. She, like many Cambridge women, could not take her eyes off Bertrand whenever she spotted him walking down King's Parade or standing about looking very well-favored during the intermissions of plays at the amateur dramatic club. Elizabeth was thus given the task of seeing whether Bertrand would be free to join us for a meal with the Cricks at Portugal Place. The time finally arranged, however, had overlapped my visit to London. When I was watching Maurice meticulously finish all the food on his plate, Odile was admiring Bertrand's perfectly proportioned face as he spoke of his problems choosing among potential social engagements during his forthcoming summer on the Riviera.
Also living at Pop's was Bertrand Fourcade, the most beautiful male, if not person, in Cambridge. Bertrand, then visiting for a few months to perfect his English, was not unconscious of his unusual beauty and so welcomed the companionship of a girl whose dress was not in shocking contrast with his well-cut clothes. As soon as I had mentioned that we knew the handsome foreigner, Odile expressed delight. She, like many Cambridge women, could not take her eyes off Bertrand whenever she spotted him walking down King's Parade or standing about looking very well-favored during the intermissions of plays at the amateur dramatic club. Elizabeth was thus given the task of seeing whether Bertrand would be free to join us for a meal with the Cricks at Portugal Place. The time finally arranged, however, had overlapped my visit to London. When I was watching Maurice meticulously finish all the food on his plate, Odile was admiring Bertrand's perfectly proportioned face as he spoke of his problems choosing among potential social engagements during his forthcoming summer on the Riviera.
This morning Francis saw that I did not have my usual interest in the French moneyed gentry. Instead, for a moment he feared that I was going to be unusually tiresome. Reporting that even a former birdwatcher could now, solve DNA was not the way to greet a friend bearing a slight hangover. However, as soon as I revealed the B-pattern details, he knew I was not pulling his leg. Especially Important was my insistence that the meridional reflection at 3.4 Å was much stronger than any other reflection. This could only mean that the 3.4 Å-thick purine and pyrimidine bases were stacked on top of each other in a direction perpendicular to the helical axis. In addition we could feel sure from both electron-microscope and X-ray evidence that the helix diameter was about 20 Å.
Francis, however, drew the line against accepting my assertion that the repeated finding of twoness in biological systems told us to build two-chain models. The way to get on, in his opinion, was to reject any argument which did not arise from the chemistry of nucleic-acid chains. Since the experimental evidence known to us could not yet distinguish between two- and three-chain models, he wanted to pay equal attention to both alternatives. Though I remained totally skeptical, I saw no reason to contest his words. I would of course start playing with two-chain models. No serious models were built, however, for several days. Not only did we lack the purine and pyrimidine components, but we had never had the shop put together any phosphorus atoms. Since our machinist needed at least three days merely to turn out the more simple phosphorus atoms, I went back to Clare after lunch to hammer out the final draft of my genetics manuscript. Later, when I cycled over to Pop's for dinner, I found Bertrand and my sister talking to Peter Pauling, who the week before had charmed Pop into giving him dining rights. In contrast to Peter, who was complaining that the Perutzes had no right to keep Nina home on a Saturday night, Bertrand and Elizabeth looked pleased with themselves. They had just returned from motoring in a friend's Rolls to a celebrated country house near Bedford. Their host, an antiquarian architect, had never truckled under to modem civilization and kept his house free of gas and electricity. In all ways possible he maintained the life of an eighteenth-century squire, even to providing special walking sticks for his guests as they accompanied him around his grounds.
Dinner was hardly over before Bertrand whisked Elizabeth on to another party, leaving Peter and me at a loss for something to do. After first deciding to work on his hi-fi set, Peter came along with me to a fi1m. This kept us in check until, 'as midnight approached, Peter held forth on how Lord Rothschild was avoiding his responsibility as a father by not inviting him to dinner with his daughter Sarah. I could not disagree, for if Peter moved into the fashionable world I might have a chance to escape acquiring a faculty-type wife.
Three days later the phosphorus atoms were ready, and I quickly strung together several short sections of the sugar-phosphate backbone. Then for a day and a half I tried to find a suitable two-chain model with the backbone in the center. All the possible models compatible with the Bform X-ray data, however, looked stereochemically even more unsatisfactory than our threechained models of fifteen months before. So, seeing Francis absorbed by his thesis, I took off the afternoon to play tennis with Bertrand. After tea I returned to point out that it was lucky I found tennis more pleasing than model building. Francis, totally indifferent to the perfect spring day, immediately put down his pencil to point out that not only was DNA very important, but he could assure me that someday I would discover the unsatisfactory nature of outdoor games.
During dinner at Portugal Place I was back in a mood to worry about what was wrong. Though I kept insisting that we should keep the backbone in the center, I knew none of my reasons held water. Finally over coffee I admitted that my reluctance to place the bases inside partially arose from the suspicion that it would be possible to build an almost infinite number of models of this type. Then we would have the impossible task of deciding whether one was right. But the real stumbling block was the bases. As long as they were outside, we did not have to consider them. If they were pushed inside, the frightful problem existed of how to pack together two or more chains with irregular sequences of bases. Here Francis had to admit that he saw not the slightest ray of light. So when I walked up out of their basement dining room into the street, I left Francis with the impression that he I would have to provide at least a semiplausible argument before I would seriously play about with base-centered mode1s. The next morning, however, as I took apart a particularly repulsive backbone-centered molecule, I decided that no harm could come from spending a few days building backbone-out models. This meant temporarily ignoring the bases, but in any case this had to happen since now another week was required before the shop could hand over the flat tin plates cut in the shapes of purines and pyrimidines.
There was no difficulty in twisting an externally situated backbone into a shape compatible with the X-ray evidence. In fact, both Francis and I had the impression that the most satisfactory angle of rotation between two adjacent bases was between 30 and 40 degrees. In contrast, an angle either twice as large or twice as small looked incompatible with the relevant bond angles. So if he backbone was on the outside, the crystallographic repeat of 34 Å had to represent the distance along the he1ical axis required for a complete rotation. At this stage Francis' interest began to perk up, and at increasing frequencies he would look up from his calculations to glance at the model. Nonetheless, neither of us had any hesitation in breaking off work for the weekend. There was a party at Trinity on Saturday night, and on Sunday Maurice was coming up to the Cricks' for a social visit arranged weeks before the arrival of the Pauling manuscript.
Maurice, however, was not allowed to forget DNA. Almost as soon as he arrived from the station, Francis started to probe him for fuller details of the B pattern. But by the end of lunch Francis knew no more than I had picked up the week before. Even the presence of Peter, saying he felt sure his father would soon spring into action, failed to ruffle Maurice's plans. Again he emphasized that he wanted to put off more model building until Rosy was gone, six weeks from then. Francis seized the occasion to ask Maurice whether he would mind if we started to play about with DNA models. When Maurice's slow answer emerged as no, he wouldn't mind, my pulse rate returned to normal. For even if the answer had been yes, our model building would have gone ahead.
There was no difficulty in twisting an externally situated backbone into a shape compatible with the X-ray evidence. In fact, both Francis and I had the impression that the most satisfactory angle of rotation between two adjacent bases was between 30 and 40 degrees. In contrast, an angle either twice as large or twice as small looked incompatible with the relevant bond angles. So if he backbone was on the outside, the crystallographic repeat of 34 Å had to represent the distance along the he1ical axis required for a complete rotation. At this stage Francis' interest began to perk up, and at increasing frequencies he would look up from his calculations to glance at the model. Nonetheless, neither of us had any hesitation in breaking off work for the weekend. There was a party at Trinity on Saturday night, and on Sunday Maurice was coming up to the Cricks' for a social visit arranged weeks before the arrival of the Pauling manuscript.
Maurice, however, was not allowed to forget DNA. Almost as soon as he arrived from the station, Francis started to probe him for fuller details of the B pattern. But by the end of lunch Francis knew no more than I had picked up the week before. Even the presence of Peter, saying he felt sure his father would soon spring into action, failed to ruffle Maurice's plans. Again he emphasized that he wanted to put off more model building until Rosy was gone, six weeks from then. Francis seized the occasion to ask Maurice whether he would mind if we started to play about with DNA models. When Maurice's slow answer emerged as no, he wouldn't mind, my pulse rate returned to normal. For even if the answer had been yes, our model building would have gone ahead.
 |
| "Evolution Says You're Weaker and More Disease Prone Than Your Ancestors" (click to learn why) |
25.
THE next few days saw Francis becoming increasingly agitated by my failure to stick close to the molecular models. It did not matter that before his tenish entrance I was usually in the lab. Almost every afternoon, knowing that I was on the tennis court, he would fretfully twist his head away from his work to see the polynucleotide backbone unattended. Moreover, after tea I would show up for only a few minutes of minor fiddling before dashing away to have sherry with the girls at Pop's. Francis' grumbles did not disturb me, however, because further refining of our latest backbone without a solution to the bases would not represent a re al step forward.
I went ahead spending most evenings at the films, vaguely dreaming that any moment the answer would suddenly hit me. Occasionally my wild pursuit of the celluloid backfired, the worst occasion being an evening set aside for Ecstasy. Peter and I had both been too young to observe the original showings of Hedy Lamarr's romps in the nude, and so on the long-awaited night we collected Elizabeth and went up to the Rex. However, the only swimming scene left intact by the English censor was an inverted reflection from a pool of water. Before the film was half over we joined the violent booing of the disgusted undergraduates as the dubbed voices uttered words of uncontrolled passion. Even during good films I found it almost impossible to forget the bases. The fact that we had at last produced a stereochemically reasonable configuration for the backbone was always in the back of my head. Moreover, there was no longer any fear that it would be incompatible with the experimental data. By then it had been checked out with Rosy's precise measurements. Rosy, of course, did not directly give us her data. For that matter, no one at King's realized they were in our hands. We came upon them because of Max's membership on a committee appointed by the Medical Research Council to look into the research activities of Randall's lab to coordinate Biophysics research within its laboratories. Since Randall wished to convince the outside committee that he had a productive research group, he had instructed his people to draw up a comprehensive summary of their accomplishments. In due time this was prepared in mimeograph form and sent routinely to all the committee members. The report was not confidential and so Max saw no reason not to give it to Francis and me. Quickly scanning its contents, Francis sensed with relief that following my return from King's I had correctly reported to him the essential features of the B pattern. Thus only minor modifications were necessary in our backbone configuration.
Generally, it was late in the evening after I got back to my rooms that I tried to puzzle out the mystery of the bases. Their formulas were written out in J. N. Davidson's little book The Biochemistry of Nucleic Acids, a copy of which I kept in Oare. So I could be sure that I had the correct structures when I drew tiny pictures of the bases on sheets of Cavendish notepaper. My aim was somehow to arrange the centrally located bases in such a way that the backbones on the outside were completely regular - that is, giving the sugar-phosphate groups of each nucleotide identical three-dimensional configurations. But each time I tried to come up with a solution I ran into the obstacle that the four bases each had a quite different shape. Moreover, there were many reasons to believe that the sequences of the bases of a given polynucleotide chain were very irregular. Thus, unless some very special trick existed, randomly twisting two polynucleotide chains around one another should result in a mess. In some places the bigger bases must touch each other, while in other regions, where the smaller bases would lie opposite each other, there must exist a gap or else their backbone regions must buckle in. There was also the vexing problem of how the intertwined chains might be held together by hydrogen bonds between the bases. Though for over a year Francis and I had dismissed the possibility that bases formed regular hydrogen bonds, it was now obvious to me that we had done so incorrectly. The observation that one or more hydrogen atoms on each of the bases could move from one location to another ( a tautomeric shift ) had initially led us to conclude that all the possible tautomeric forms of a given base occurred in equal frequencies. But a recent rereading of J. M. Gulland's and D. 0. Jordan's papers on the acid and base titrations of DNA made me finally appreciate the strength of their conclusion that a large fraction, if not all, of the bases formed hydrogen bonds to other bases. Even more important, these hydrogen bonds were present at very low DNA concentrations, strongly hinting that the bonds linked together bases in the same molecule. There was in addition the X-ray crystallographic result that each pure base so far examined formed as many irregular hydrogen bonds as stereochemically possible. Thus, conceivably the crux of the matter was a rule governing hydrogen bonding between bases.
My doodling of the bases on paper at first got nowhere, regardless of whether or not I had been to a film. Even the necessity to expunge Ecstasy from my mind did not lead to passable hydrogen 'bonds, and I fell asleep hoping that an undergraduate party the next afternoon at Downing would be full of pretty girls. But my expectations were dashed as soon as I arrived to spot a group of healthy hockey players and several pallid debutantes. Bertrand also instantly perceived he was out of place, and as we passed a polite interval before scooting out, I explained how I was racing Peter's father for the Nobel Prize. Not until the middle of the next week, however, did a nontrivial idea emerge. It came while I was drawing the, fused rings of adenine on paper. Suddenly I realized the ~potentially profound implications of a DNA structure in which the adenine residue formed hydrogen bonds similar to those found in crystals of pure adenine. If DNA was, like this, each adenine residue would form two hydrogen bonds to an adenine residue related to it by a 180-degree rotation. Most important, two symmetrical hydrogen bonds could also hold together pairs of guanine, cytosine, or thymine. I thus started wondering whether each DNA molecule consisted of two chains with identical base sequences held together by hydrogen bonds between pairs of identical bases. There was the complication, however, that such a structure could not have 'a regu1ar backbone, since the purines ( adenine and guanine ) and the pyrimidines ( thymine and cytosine ) have different shapes. The resulting backbone would have to show minor in-and-out buckles depending upon whether pairs of purines or pyrimidines were m the center.
I went ahead spending most evenings at the films, vaguely dreaming that any moment the answer would suddenly hit me. Occasionally my wild pursuit of the celluloid backfired, the worst occasion being an evening set aside for Ecstasy. Peter and I had both been too young to observe the original showings of Hedy Lamarr's romps in the nude, and so on the long-awaited night we collected Elizabeth and went up to the Rex. However, the only swimming scene left intact by the English censor was an inverted reflection from a pool of water. Before the film was half over we joined the violent booing of the disgusted undergraduates as the dubbed voices uttered words of uncontrolled passion. Even during good films I found it almost impossible to forget the bases. The fact that we had at last produced a stereochemically reasonable configuration for the backbone was always in the back of my head. Moreover, there was no longer any fear that it would be incompatible with the experimental data. By then it had been checked out with Rosy's precise measurements. Rosy, of course, did not directly give us her data. For that matter, no one at King's realized they were in our hands. We came upon them because of Max's membership on a committee appointed by the Medical Research Council to look into the research activities of Randall's lab to coordinate Biophysics research within its laboratories. Since Randall wished to convince the outside committee that he had a productive research group, he had instructed his people to draw up a comprehensive summary of their accomplishments. In due time this was prepared in mimeograph form and sent routinely to all the committee members. The report was not confidential and so Max saw no reason not to give it to Francis and me. Quickly scanning its contents, Francis sensed with relief that following my return from King's I had correctly reported to him the essential features of the B pattern. Thus only minor modifications were necessary in our backbone configuration.
Generally, it was late in the evening after I got back to my rooms that I tried to puzzle out the mystery of the bases. Their formulas were written out in J. N. Davidson's little book The Biochemistry of Nucleic Acids, a copy of which I kept in Oare. So I could be sure that I had the correct structures when I drew tiny pictures of the bases on sheets of Cavendish notepaper. My aim was somehow to arrange the centrally located bases in such a way that the backbones on the outside were completely regular - that is, giving the sugar-phosphate groups of each nucleotide identical three-dimensional configurations. But each time I tried to come up with a solution I ran into the obstacle that the four bases each had a quite different shape. Moreover, there were many reasons to believe that the sequences of the bases of a given polynucleotide chain were very irregular. Thus, unless some very special trick existed, randomly twisting two polynucleotide chains around one another should result in a mess. In some places the bigger bases must touch each other, while in other regions, where the smaller bases would lie opposite each other, there must exist a gap or else their backbone regions must buckle in. There was also the vexing problem of how the intertwined chains might be held together by hydrogen bonds between the bases. Though for over a year Francis and I had dismissed the possibility that bases formed regular hydrogen bonds, it was now obvious to me that we had done so incorrectly. The observation that one or more hydrogen atoms on each of the bases could move from one location to another ( a tautomeric shift ) had initially led us to conclude that all the possible tautomeric forms of a given base occurred in equal frequencies. But a recent rereading of J. M. Gulland's and D. 0. Jordan's papers on the acid and base titrations of DNA made me finally appreciate the strength of their conclusion that a large fraction, if not all, of the bases formed hydrogen bonds to other bases. Even more important, these hydrogen bonds were present at very low DNA concentrations, strongly hinting that the bonds linked together bases in the same molecule. There was in addition the X-ray crystallographic result that each pure base so far examined formed as many irregular hydrogen bonds as stereochemically possible. Thus, conceivably the crux of the matter was a rule governing hydrogen bonding between bases.
My doodling of the bases on paper at first got nowhere, regardless of whether or not I had been to a film. Even the necessity to expunge Ecstasy from my mind did not lead to passable hydrogen 'bonds, and I fell asleep hoping that an undergraduate party the next afternoon at Downing would be full of pretty girls. But my expectations were dashed as soon as I arrived to spot a group of healthy hockey players and several pallid debutantes. Bertrand also instantly perceived he was out of place, and as we passed a polite interval before scooting out, I explained how I was racing Peter's father for the Nobel Prize. Not until the middle of the next week, however, did a nontrivial idea emerge. It came while I was drawing the, fused rings of adenine on paper. Suddenly I realized the ~potentially profound implications of a DNA structure in which the adenine residue formed hydrogen bonds similar to those found in crystals of pure adenine. If DNA was, like this, each adenine residue would form two hydrogen bonds to an adenine residue related to it by a 180-degree rotation. Most important, two symmetrical hydrogen bonds could also hold together pairs of guanine, cytosine, or thymine. I thus started wondering whether each DNA molecule consisted of two chains with identical base sequences held together by hydrogen bonds between pairs of identical bases. There was the complication, however, that such a structure could not have 'a regu1ar backbone, since the purines ( adenine and guanine ) and the pyrimidines ( thymine and cytosine ) have different shapes. The resulting backbone would have to show minor in-and-out buckles depending upon whether pairs of purines or pyrimidines were m the center.
 |
| Fig. 6. A schematic view of a DNA molecule built up from like with-like base pairs. |
Despite the messy backbone, my pulse began to race. If this was DNA, I should create a bombshell by announcing its discovery. The existence of two intertwined chains with identical base sequences could not be a chance matter. Instead it would strongly suggest that one chain in each molecule had at some earlier stage served as the template for the synthesis of the other chain. Under this scheme, gene replication starts with the separation of its two identical chains. Then two new daughter strands are made on the two parental templates, thereby forming two DNA molecules identical to the original molecule. Thus, the essential trick of gene replication could come from the requirement that each base in the newly synthesized chain always hydrogen-bonds to an identical, base. That night, however, I could not see why the common tautomeric form of guanine would not hydrogen-bond to adenine. Likewise, several other pairing mistakes should also occur. But since there was no reason to rule out the participation of specific enzymes, I saw no need to be unduly disturbed. For example, there might exist an enzyme specific for adenine that caused adenine always to be inserted opposite an adenine residue on the template strands.
As the clock went past midnight I was becoming more and more pleased. There had been far too many days when Francis and I worried that the DNA structure I might turn out to be superficially very dull, suggesting nothing about either its replication or its function in controlling cell biochemistry. But now, to my delight and I amazement, the answer was turning out to be profoundly interesting. For over two hours I happily lay awake with pairs of adenine residues whirling in front of my closed eyes. Only for brief moments did the fear shoot through me that an idea this good could be wrong.
As the clock went past midnight I was becoming more and more pleased. There had been far too many days when Francis and I worried that the DNA structure I might turn out to be superficially very dull, suggesting nothing about either its replication or its function in controlling cell biochemistry. But now, to my delight and I amazement, the answer was turning out to be profoundly interesting. For over two hours I happily lay awake with pairs of adenine residues whirling in front of my closed eyes. Only for brief moments did the fear shoot through me that an idea this good could be wrong.
 |
| Fig. 7. The four base pairs used to construct the like-with-like structure (hydrogen bonds are dotted). |
26.
My scheme was tom to shreds by the following noon. Against me was the awkward chemical fact that I had chosen the wrong tautomeric forms of guanine and thymine. Before the disturbing truth came out, I had eaten a hurried breakfast at the Whim, then momentarily gone, back to Clare to reply to a letter from Max Debunk which reported that my manuscript on bacterial genetics looked unsound to the Cal Tech geneticists. Nevertheless, he would accede to my request that he send it to the Proceedings of the National Academy. In this way, I would still be young when I committed the folly of publishing a silly idea. Then I could sober up before my career was permanently fixed on a reckless course. At first this message had its desired unsettling effect. But now, with my spirits soaring on the possibility that I had the self-duplicating structure, I reiterated my faith that I knew what happened when bacteria mated. Moreover, I could not refrain from adding a sentence saying that I had just devised a beautiful DNA structure which was completely different from Pauling's. For a few seconds I considered giving some details of what I was up to, but since I was in a rush I decided not to, quickly dropped the letter in the box, and dashed off to the lab.
The letter was not in the post for more than an hour before I knew that my claim was nonsense. I no sooner got to the office and began explaining my scheme than the American crystallographer Jerry Donohue protested that the idea would not work. The tautomeric forms I had copied out of Davidson's book were, in Jerry's opinion, incorrectly assigned. My immediate retort that several other texts also pictured guanine and thymine in the enol form cut no ice with Jerry. Happily he let out that for years organic chemists had been arbitrarily favoring particular tautomeric forms over their alternatives on only the flimsiest of grounds. In fact, organic-chemistry text books were littered with pictures of highly improbable tautomeric forms. The guanine picture I was thrusting toward I his face was almost certainly bogus. All his chemical intuition told him that it would occur in the keto form. He was just as sure that thymine was also wrongly assigned an enol configuration. Again he strongly favored the keto alternative.
The letter was not in the post for more than an hour before I knew that my claim was nonsense. I no sooner got to the office and began explaining my scheme than the American crystallographer Jerry Donohue protested that the idea would not work. The tautomeric forms I had copied out of Davidson's book were, in Jerry's opinion, incorrectly assigned. My immediate retort that several other texts also pictured guanine and thymine in the enol form cut no ice with Jerry. Happily he let out that for years organic chemists had been arbitrarily favoring particular tautomeric forms over their alternatives on only the flimsiest of grounds. In fact, organic-chemistry text books were littered with pictures of highly improbable tautomeric forms. The guanine picture I was thrusting toward I his face was almost certainly bogus. All his chemical intuition told him that it would occur in the keto form. He was just as sure that thymine was also wrongly assigned an enol configuration. Again he strongly favored the keto alternative.
 |
| Fig. 8. The contrasting tautomeric forms of guanine and thymine which might occur in DNA. The hydrogen atoms that can undergo the changes in position (a tautomeric shift) are shaded. |
Jerry, however, did not give a foolproof reason for preferring the keto forms. He admitted that only one crystal structure bore on the problem. This was diketopiperazine, whose threedimensional configuration had been carefully worked out in Pauling's lab several years before. I Here there was no doubt that the keto form, not the enol, was present. Moreover, he felt sure that the quantum-mechanical arguments which showed why diketopiperazine has the keto form should also hold for guanine and thymine. I was thus firmly urged not to waste more time with my harebrained scheme. Though my immediate reaction was to hope that Jerry was blowing hot air, I did not dismiss his criticism. Next to Linus himself, Jerry knew more about hydrogen bonds than anyone else in the world. Since for many years he had worked at Cal Tech on the crystal structures of small organic molecules, I couldn't kid myse1f that he did not grasp our problem. During the six months that he occupied a desk in our office, I had never heard him shooting off his mouth on subjects about which he knew nothing.
Thoroughly worried, I went back to' my desk hoping that some gimmick might emerge to salvage the like-with-like idea. But it was obvious that the new assignments were its death blow. Shifting the hydrogen atoms to their keto locations made the size differences between the purines and pyrimidines even more important than would be the case if the enol forms existed. Only by the most special pleading could I imagine the polynucleotide backbone bending enough to accommodate irregular base sequences. Even this possibility vanished when Francis came in. He immediately realized that a like-with-like structure would give a 34 Å crystallographic repeat only if each chain had a complete rotation every 68 Å. But this would mean that the rotation angle between successive bases would be only 18 degrees, a value Francis believed was absolutely ru1ed out by his recent fiddling with the models. Also Francis did not like the fact that the structure gave no explanation for the Chargaff rules ( adenine equals thymine, guanine equals cytosine ). I, however, maintained my lukewarm response to Chargaff's data. So I. welcomed the arrival of lunchtime, when Francis' cheerful prattle temporarily shifted my thoughts to why undergraduates could not satisfy au pair girls. After lunch I was not anxious to return to work, for I was afraid that in trying to fit the keto forms into some new scheme I would run into a stone wall and have to face the fact that no regu1ar hydrogen-bonding scheme was compatible with the X-ray evidence. As long as I remained outside gazing at the crocuses, hope could be maintained that some pretty base arrangement would fall out. Fortunately, when we walked upstairs, I found that I had an excuse to put off the crucial model-building step for at least several more hours.
The metal purine and pyrimidine models, needed for systematically checking all the conceivable hydrogen-bonding possibilities, had not been finished on time. At least two more days were needed before they would be in our hands. This was much too long even for me to remain in limbo, so I spent the rest of the afternoon cutting accurate representations of the bases out of stiff cardboard. But by the time they were ready I realized that the answer must be put off till the next day. After dinner I was to join a group from Pop's at the theater. When I got to our still empty office the following morning, I quickly cleared away the papers from my desk top so that I would have a large, flat surface on which to form pairs of bases held together by hydrogen bonds. Though I initially went back to my like-with-like prejudices, 1 saw all too well that they led nowhere. When Jerry came in I looked up, saw that it was not Francis, and began shifting the bases in and out of various other pairing possibilities. Suddenly I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair held together by at least two hydrogen bonds. All the hydrogen bonds seemed to form naturally; no fudging was required to make the two types of base pairs identical in shape. Quickly I called Jerry over to ask him whether this time he had any objection to my new base pairs.
The metal purine and pyrimidine models, needed for systematically checking all the conceivable hydrogen-bonding possibilities, had not been finished on time. At least two more days were needed before they would be in our hands. This was much too long even for me to remain in limbo, so I spent the rest of the afternoon cutting accurate representations of the bases out of stiff cardboard. But by the time they were ready I realized that the answer must be put off till the next day. After dinner I was to join a group from Pop's at the theater. When I got to our still empty office the following morning, I quickly cleared away the papers from my desk top so that I would have a large, flat surface on which to form pairs of bases held together by hydrogen bonds. Though I initially went back to my like-with-like prejudices, 1 saw all too well that they led nowhere. When Jerry came in I looked up, saw that it was not Francis, and began shifting the bases in and out of various other pairing possibilities. Suddenly I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair held together by at least two hydrogen bonds. All the hydrogen bonds seemed to form naturally; no fudging was required to make the two types of base pairs identical in shape. Quickly I called Jerry over to ask him whether this time he had any objection to my new base pairs.
 |
| Fig. 9. The adenine-thymine and guanine-cytosine base pairs used to construct the double helix (hydrogen bonds are dotted). The formation of a third hydrogen bond between guanine and cytosine was considered, but rejected because a crystallographic study of guanine hinted that it would be very weak. Now this conjecture is known to be wrong. Three strong hydrogen bonds can be drawn between guanine and cytosine. |
When he said no, my morale skyrocketed, for I suspected that we now had the answer to the riddle of why the number of purine residues exactly equaled the number of pyrimidine residues. Two irregular sequences of bases could be regularly packed in the center of a helix if a purine always hydrogen-bonded to a pyrimidine. Furthermore, the hydrogen-bonding requirement meant that adenine would always pair with thymine, while guanine could pair only with cytosine. Chargaff's rules then suddenly stood out as a consequence of a double-helical structure for DNA. Even more exciting, this type of double helix suggested a replication scheme much more satisfactory than my briefly considered like-with-like pairing. Always pairing adenine with thymine and guanine with cytosine meant that the base sequences of the two intertwined chains were complementary to each other. Given the base sequence of one chain, that of its partner was automatically determined. Conceptually, it was thus very easy to visualize how a single chain could be the template for the synthesis of a chain with the complementary sequence. Upon his arrival Francis did not get more than halfway through the door before I let loose that the answer to everything was in our hands. Though as a matter of principle he maintained skepticism for a few moments, the similarly shaped A-T and G-C pairs had their expected impact. His quickly pushing the bases together in a number of different ways did not reveal any other way to satisfy Chargaff's rules. A few minutes later he spotted the fact that the two glycosidic bonds (joining base and sugar) of each base pair were systematically related by a diad axis perpendicular to the helical axis. Thus, both pairs could be flipflopped over and still have their glycosidic bonds facing in the same direction. This had the important consequence that a given chain could contain both purines 'and pyrimidines. At the same time, it strongly suggested that the backbones of the two chains must run in opposite directions. The question then became whether the A-T and G-C base pairs would easily fit the backbone configuration devised during the previous two weeks. At first glance this looked like a good bet, since I had left free in the center a large vacant area for the bases. However, we both knew that we would not be home until a complete model was built in which all the stereochemical contacts were satisfactory. There was also the obvious fact that the implications of its existence were far too important to risk crying wo1f. Thus I felt slightly queasy when at lunch Francis winged into the Eagle to tell everyone within hearing distance that we had found the secret of life.
 |
| "More on Junk DNA by Steven Novella" (Click to read more about) |
27.
FRANCIS' preoccupation with DNA quickly became fulltime. The first afternoon following the discovery that A-T and G-C base pairs had similar shapes, he went back to his thesis measurements, but his effort was ineffectual. Constantly he would pop up from his chair, worriedly look at the cardboard models, fiddle with other combinations, and then, the period of momentary uncertainty over, look satisfied and tell me how important our work was. I enjoyed Francis' words, even though they lacked the casual sense of understatement known to be the correct way to behave in Cambridge. It seemed almost unbelievable that the DNA structure was solved, that the answer was incredibly exciting, and that our names would be associated with the double helix as Pauling's was with the alpha helix. When the Eagle opened at six, I went over with Francis to talk about what must be done in the next few days. Francis wanted no time lost in seeing whether a satisfactory three-dimensional model could be built, since the geneticists and nucleic-acid biochemists should not misuse their time and facilities any longer than necessary. They must be told the answer quickly, so that they could reorient their research upon our work. Though I was equally anxious to build the complete model, I thought more about Linus and the possibility that he might stumble upon the base pairs before we told him the answer.
Only a little encouragement was needed to get the final soldering accomplished in the next couple of hours. The brightly shining metal plates were then immediately used to make a model in which for the first time all the DNA components were present. In about an hour I had arranged the atoms in positions which satisfied both the X-ray data and the laws of stereochemistry. The resulting helix was right-handed with the two chains running in opposite directions. Only one person can easily play with a model, and so Francis did not try to check my work until I backed away and said that I thought everything fitted. While one interatomic contact was slightly shorter than optimal, it was not out of line with several published values, and I was not disturbed. Another fifteen minutes' fiddling by Francis failed to find anything wrong, though for brief intervals my stomach felt uneasy when 1 saw him frowning. In each case he became satisfied and moved on to verify that another interatomic contact was reasonable. Everything thus looked very good when we went back to have supper with Odile. Our dinner words fixed on how to let the big news out. Maurice, especially, must soon be told. But remembering the fiasco of sixteen months before, keeping King's in the dark made sense until exact coordinates had been obtained for all the atoms. It was all too easy to fudge a successful series of atomic contacts so that, while each looked almost acceptable, the whole collection was energetically impossible. We suspected that we had not made this error, but our judgment conceivably might be biased by the biological advantages of complementary DNA molecules. Thus the next several days were to be spent using a plumb line and a measuring stick to obtain the relative positions of all atoms in a single nucleotide. Because of the helical symmetry, the locations of the atoms in one nucleotide would automatically generate the other positions. After coffee Odile wanted to know whether they would still have to go into exile in Brooklyn if our work was as sensational as everyone told her. Perhaps we should stay on in Cambridge to solve other problems of equal importance. I tried to reassure her, emphasizing that not 'all American men cut all their hair off and that there were scores of American women who did not wear short white socks on the streets. I had less success arguing that the States' greatest virtue was its wide-open spaces where people never went. Odile looked in horror at the prospect of being long without fashionably dressed people. Moreover, she could not believe that I was serious, since I had just had a tailor cut a tightly fitting blazer, unconnected with the sacks that Americans draped on their shoulders.
The next morning I again found that Francis had beaten me to the lab. He was already at work tightening the model on its support stands so that he could read off the atomic coordinates. While he moved the atoms back and forth, I sat on the top of my desk thinking about the form of the letters that I soon could write, saying that we had found something interesting. Occasionally, Francis would look disgusted when my daydreams kept me from observing that he needed my help to keep the model from collapsing as he rearranged the supporting ring stands.
 |
| Fig. 10. A schematic illustration of the double helix. The two sugar-phosphate backbones twist about on the outside with the flat hydrogen-bonded base pairs forming the core. Seen this way, the structure resembles a spiral staircase with the base pairs forming the steps. |
By then we knew that all my previous fuss about the importance of Mg++ ions was misdirected. Most likely Maurice and Rosy were right in insisting that they were looking at the Na+ salt of DNA. But with the sugar-phosphate backbone on the outside, it did not matter which salt was present. Either would fit perfectly well into the double helix. Bragg had his first look late that morning. For several days he had been home with the flu and was in bed when he heard that Crick and I had thought up an ingenious DNA structure which might be important to biology. During his first free moment back in the Cavendish he slipped away from his office for a direct view. Immediately he caught on to the complementary relation between the two chains and saw how an equivalence of adenine with thymine and guanine with cytosine was a logical consequence of the regular repeating shape of the sugar-phosphate backbone. As he was not aware of Chargaff's rules, I went over the experimental evidence on the relative proportions of the various bases, noticing that he was becoming increasingly excited by its potential implications for gene replication. When the question of the X-ray evidence came up, he saw why we had not yet called up the King's group. He was bothered, however, that we had not yet asked Todd's opinion. Telling Bragg that we had got the organic chemistry straight did not put him completely at ease. The chance that we were using the wrong chemical formula admittedly was small, but, since Crick talked so fast, Bragg could never be sure that he would ever slow down long enough to get the right facts. So it was arranged that as soon as we had a set of atomic coordinates, we would have Todd come over.
The final refinements of the coordinates were finished the following evening. Lacking the exact X-ray evidence, we were not confident that the configuration chosen was precisely correct. But this did not bother us, for we only wished to establish that at least one specific two-chain complementary helix was stereochemically possible. Until this was clear, the objection could be raised that, although our idea was aesthetically elegant, the shape of the sugar-phosphate backbone might not permit its existence. Happily, now we knew that this was not true, and so we had lunch, telling each other that a structure this pretty just had to exist. With the tension now off, I went to play tennis with Bertrand, telling Francis that later in the afternoon I would write Luria and Delbrück about the double helix. It was so arranged that John Kendrew would call up Maurice to say that he should come out to see what Francis and I had just devised. Neither Francis nor I wanted the task. Earlier in the day the post had brought a note from Maurice to Francis, mentioning that he was now about to go full steari1 ahead on DNA and intended to place emphasis on model building.
 |
| "End of genetic diseases? Congenital heart disease removed from embryos for the first time!" (Click and read more about) |
28.
MAURICE needed but a minute's look at the model to like it. He had been forewarned by John that it was a two-chain affair, held together by the A-T and G-C base pairs, and so immediately upon entering our office he studied its detailed features. That it had two, not three, chains did not bother him since he knew the evidence never seemed clear-cut. While Maurice silently stared at the meta1 object, Francis stood by, sometimes talking very fast about what sort of X-ray diagram the structure should produce, then becoming strangely noiseless when he perceived that Maurice's wish was to look at the double he1ix, not to receive a lecture in crystallographic theory which he could work out by himself. There was no questioning of the decision to put guanine and thymine in the keto form. Doing otherwise would destroy the base pairs, and he accepted Jerry Donohue's spoken argument as if it were a commonplace. The unforeseen dividend of having Jerry share an office with Francis, Peter, and me, though obvious to all, was not spoken about. If he had not been with us in Cambridge, I might still have been pumping for a like-with-like structure. Maurice, in a lab devoid of structural chemists, did not have anyone about to tell him that all the textbook pictures were wrong. But for Jerry, only Pauling would have been likely to make the right choice and stick by its consequences. The next scientific step was to compare seriously the experimental X-ray data with the diffraction pattern predicted by our model. Maurice went back to London, saying that he would soon measure the critical reflections. There was not a hint of bitterness in his voice, and I felt quite relieved. Until the visit I had remained apprehensive that he would look gloomy, being unhappy that we had seized part of the glory that should have gone in full to him and his younger colleagues. But there was no trace of resentment on his face, and in his subdued way he was thoroughly excited that the structure would prove of great benefit to biology.
He was back in London only two days before he rang up to say that both he and Rosy found that their X-ray data strongly supported the double helix. They were quickly writing up their results and wanted to publish simultaneously with our announcement of the base pairs. Nature was a place for rapid publication, since if both Bragg and Randall strongly supported the manuscripts they might be published within a month of their receipt. However, there would not be only one paper from King's. Rosy and Gosling would report their results separately from Maurice and his collaborators. Rosy's instant acceptance of our model at first amazed me. I had feared that her sharp, stubborn mind, caught in her self-made antihelical trap, might dig up irrelevant results that would foster uncertainty about the correctness of the double helix. Nonetheless, like almost everyone else, she saw the appeal of the base pairs and accepted the fact that the structure was too pretty not to be true. Moreover, even before she learned of our proposal, the X-ray evidence had been forcing her more than she cared to admit toward a helical structure. The positioning of the backbone on the outside of the molecule was demanded by her evidence and, given the necessity to hydrogen-bond the bases together, the uniqueness of the A-T and G-C pairs was a fact she saw no reason to argue about.
At the same time, her fierce annoyance with Francis and me collapsed. Initially we were hesitant to discuss the double helix with her, fearing the testiness of our previous encounters. But Francis noticed her changed attitude when he was in London to talk with Maurice about details of the X-ray pictures. Thinking that Rosy wanted nothing to do with him, he spoke largely to Maurice, until he slowly perceived that Rosy wanted his crystallographic advice and was prepared to exchange unconcealed hostility for conversation between equals. With obvious pleasure Rosy showed Francis her data, and for the first time he was able to see how foolproof was her assertion that the sugar-phosphate backbone was on the outside of the molecule. Her past uncompromising statements on this matter thus reflected first-rate science, not the outpourings of a misguided feminist.
He was back in London only two days before he rang up to say that both he and Rosy found that their X-ray data strongly supported the double helix. They were quickly writing up their results and wanted to publish simultaneously with our announcement of the base pairs. Nature was a place for rapid publication, since if both Bragg and Randall strongly supported the manuscripts they might be published within a month of their receipt. However, there would not be only one paper from King's. Rosy and Gosling would report their results separately from Maurice and his collaborators. Rosy's instant acceptance of our model at first amazed me. I had feared that her sharp, stubborn mind, caught in her self-made antihelical trap, might dig up irrelevant results that would foster uncertainty about the correctness of the double helix. Nonetheless, like almost everyone else, she saw the appeal of the base pairs and accepted the fact that the structure was too pretty not to be true. Moreover, even before she learned of our proposal, the X-ray evidence had been forcing her more than she cared to admit toward a helical structure. The positioning of the backbone on the outside of the molecule was demanded by her evidence and, given the necessity to hydrogen-bond the bases together, the uniqueness of the A-T and G-C pairs was a fact she saw no reason to argue about.
At the same time, her fierce annoyance with Francis and me collapsed. Initially we were hesitant to discuss the double helix with her, fearing the testiness of our previous encounters. But Francis noticed her changed attitude when he was in London to talk with Maurice about details of the X-ray pictures. Thinking that Rosy wanted nothing to do with him, he spoke largely to Maurice, until he slowly perceived that Rosy wanted his crystallographic advice and was prepared to exchange unconcealed hostility for conversation between equals. With obvious pleasure Rosy showed Francis her data, and for the first time he was able to see how foolproof was her assertion that the sugar-phosphate backbone was on the outside of the molecule. Her past uncompromising statements on this matter thus reflected first-rate science, not the outpourings of a misguided feminist.
 |
| Fig. 11. The manner envisaged for DNA replication, given the complementary nature of the base sequences in the two chains. |
Delbrück's comments were passed on immediately to Pauling, who quickly wrote off a letter to me. The first part betrayed nervousness ─ it did not come to the point, but conveyed an invitation to participate in a meeting on proteins to which he had decided to add a section on nucleic acids. Then he came out and asked for the details of the beautiful new structure I had written Delbrück about. Reading his letter, I drew a deep breath, for I realized that Delbrück did not know of the complementary double helix at the time of Linus' talk. Instead, he was referring to the like-with-1ike idea. Fortunately, by the time my letter reached Cal Tech the base pairs had fallen out. If they had not, I would have been in the dreadful position of having to inform Delbrück and Pauling that I had impetuously written of an idea which was only twelve hours old and lived only twenty-four before it was dead. Todd made his official visit late in the week, coming over from the chemical laboratory with several younger colleagues. Francis' quick verbal tour through the structure and its implications lost none of its zest for having been given several times each day for the past week. The pitch of his excitement was rising each day, and generally, whenever Jerry or I heard the voice of Francis shepherding in some new faces, we left our office until the new converts were let out and some traces of orderly work could resume. Todd was a different matter, for I wanted to hear him tell Bragg that we had correctly followed his advice on the chemistry of the sugar-phosphate backbone. Todd also went along with the keto configurations, saying that his organic-chemist friends had drawn enol groups for purely arbitrary reasons. Then he went off, after congratulating me and Francis for our excellent chemical work.
Soon I left Cambridge to spend a week in Paris. A trip to Paris to be with Boris and Harriet Ephrussi had been arranged some weeks earlier. Since the main part of our work seemed finished, I saw no reason to postpone a visit which now had the bonus of letting me be the first to tell Ephrussi's and Lwoff's labs about the double helix. Francis, however, was not happy, telling me that a week was far too long to abandon work of such extreme significance. A call for seriousness, however, was not to my liking ─ especially when John had just shown Francis and me a letter from Chargaff in which we were mentioned. A postscript asked for information on what his scientific clowns were up to.
 |
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PAULING first heard about the double helix from Delbrück. At the bottom of the letter that broke the news of the complementary chains, I had asked that he not tell Linus. I was still slightly afraid something would go wrong and did not want Pauling to think about hydrogen-bonded base pairs until we had a few more days to digest our position. My request, however, was ignored. Delbrück wanted to tell everyone in his lab and knew that within hours the gossip would travel from his lab in biology to their friends working under Linus. Also, Pauling had made him promise to let him know the minute he heard from me. Then there was the even more important consideration that Delbrück hated any form of secrecy in scientific matters and did not want to keep Pauling in suspense any longer. Pauling's reaction was one of genuine thrill, as was Delbrück's. In almost any other situation Pauling would have fought for the good points of his idea. The overwhelming biological merits of a se1f-complementary DNA molecule made him effectively concede the race. He did want, however, to see the evidence from King's before he considered the matter a closed book. This he hoped would be possible three weeks hence, when he would come to Brussels for a Solvay meeting on proteins in the second week of Apri1.
That Pauling was in the know came out in a letter from Delbrück, arriving just after I returned from Paris on March 18. By then we didn't mind, for the evidence favoring the base pairs was steadily mounting. A key piece of information was picked up at the Institute Pasteur. There I ran into Gerry Wyatt, a Canadian biochemist who knew much about the base ratios of DNA. He had just analyzed the DNA from the T2, T4, and T6 group of phages. For the past two years this DNA was said to have the strange property of lacking cytosine, a feature obviously impossible for our model. But Wyatt now said that he, together with Seymour Cohen and A1 Hershey had evidence that these phages contained a modified type of cytosine called S-hydroxy-methyl cytosine. Most important, its amount equaled the amount of guanine. This beautifully supported the double he1ix, since 5-hydroxy-methyl cytosine should hydrogen-bond like cytosine. Also pleasing was the great accuracy of the data, which illustrated better than any previous analytical work the equality of adenine and thymine and guanine with cytosine.
While I was away Francis had taken up the structure of the DNA molecule in the A form. Previous work in Maurice's lab had shown that crystalline A-form DNA fibers increase in length when they take up water and go over into the B form. Francis guessed that the more compact A form was achieved by tilting the base pairs thereby decreasing the translational distance of a base pair along the fiber axis to about 2.6 Ǻ. He thus set about building a model with tilted bases. Though this proved more difficult to fit together than the more open B structure, a satisfactory A model awaited me upon my return. In the next week the first drafts of our Nature paper got handed out and two were sent down to London for comments from Maurice and Rosy. They had no real objections except for wanting us to mention that Fraser in their lab had considered hydrogen-bonded bases prior to our work. His schemes until then unknown to us in detail, always dealt with groups of three bases, hydrogen-bonded in thy middle, many of which we now knew to be in the wrong tautomeric forms. Thus his idea did not seem worth resurrecting only to be quickly buried. However, when Maurice sounded upset at our objection, we added the necessary reference. Both Rosy's and Maurice's papers covered roughly the same ground and in each case interpreted their results in terms of the base pairs. For a while Francis wanted to expand our note to write at length about the biological implications. But finally he saw the point to a short remark and composed the sentence: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
Sir Lawrence was shown the paper in its nearly final form. After suggesting a minor stylistic alteration, he enthusiastically expressed his willingness to post it to Nature with a strong covering letter. The solution to the structure was bringing genuine happiness to Bragg. That the result came out of the Cavendish and not Pasadena was obviously a factor. More important was the unexpectedly marvelous nature of the answer, and the fact that the X-ray method he had developed forty years before was at the heart of a profound insight into the nature of life itself. The final version was ready to be typed on the last weekend of March. Our Cavendish typist was not on hand, and the brief job was given to my sister. There was no problem persuading her to spend a Saturday afternoon this way, for we told her that she was participating in perhaps the most famous event in biology since Darwin's book. Francis and I stood over her as she typed the ninehundred-word article that began, "We wish to suggest a structure for the salt of deoxyribose nucleic acid (DNA). This structure has novel features which are of considerable biological interest." On Tuesday the manuscript was sent up to Bragg's office and on Wednesday, Apri12, went off to the editors of Nature.
Linus arrived in Cambridge on Friday night. On his way to Brussels for the Solvay meeting, he stopped off both to see Peter and to look at the model. Unthinkingly Peter arranged for him to stay 'at Pop's. Soon we found that he would have preferred a hotel. The presence of foreign girls at breakfast did not compensate for the lack of hot water in his room. Saturday morning Peter brought him into the office, where, after greeting Jerry with Cal Tech news, he set about examining the model. Though he still wanted to see the quantitative measurements of the King's lab, we supported our argument by showing him a copy of Rosy's original B photograph. All the right cards were in our hands and so, gracefully, he gave his opinion that we had the answer. Bragg then came in to get Linus so that he could take him and Peter to his house for lunch. That night both Paulings, together with Elizabeth and me, had dinner with the Cricks at Portugal Place. Francis, perhaps because of Linus' presence, was mildly muted and let Linus be charming to my sister and Odile. Though we drank a fair amount of Burgundy, the conversation never got animated and I felt that Pauling would rather talk to me, clearly an unfinished member of the younger generation, than to Francis. The talk did not last long, since Linus, still on California time, was becoming tired, and the party was over at midnight.
E1izabeth and I flew off the following afternoon to Paris, where Peter would join us the next day. Ten days hence she was sailing to the States on her way to Japan to marry an American she had known in college. These were to be our last days together, at least in the carefree spirit that had marked our escape from the Middle West and the American culture it was so easy to be ambivalent about. Monday morning we went over to the Faubourg St. Honoré for our last look at its elegance. There, peering in at a shop full of sleek umbrellas, I realized one should be her wedding present and we quickly had it. Afterwards she searched out a friend for tea while I walked back across the Seine to our hotel near the Palis du Luxembourg. Later that night with Peter we would celebrate my birthday. But now I was alone, looking at the longhaired girls near St. Germain des Prés and knowing they were not for me. I was twenty-five and too old to be unusual.
That Pauling was in the know came out in a letter from Delbrück, arriving just after I returned from Paris on March 18. By then we didn't mind, for the evidence favoring the base pairs was steadily mounting. A key piece of information was picked up at the Institute Pasteur. There I ran into Gerry Wyatt, a Canadian biochemist who knew much about the base ratios of DNA. He had just analyzed the DNA from the T2, T4, and T6 group of phages. For the past two years this DNA was said to have the strange property of lacking cytosine, a feature obviously impossible for our model. But Wyatt now said that he, together with Seymour Cohen and A1 Hershey had evidence that these phages contained a modified type of cytosine called S-hydroxy-methyl cytosine. Most important, its amount equaled the amount of guanine. This beautifully supported the double he1ix, since 5-hydroxy-methyl cytosine should hydrogen-bond like cytosine. Also pleasing was the great accuracy of the data, which illustrated better than any previous analytical work the equality of adenine and thymine and guanine with cytosine.
While I was away Francis had taken up the structure of the DNA molecule in the A form. Previous work in Maurice's lab had shown that crystalline A-form DNA fibers increase in length when they take up water and go over into the B form. Francis guessed that the more compact A form was achieved by tilting the base pairs thereby decreasing the translational distance of a base pair along the fiber axis to about 2.6 Ǻ. He thus set about building a model with tilted bases. Though this proved more difficult to fit together than the more open B structure, a satisfactory A model awaited me upon my return. In the next week the first drafts of our Nature paper got handed out and two were sent down to London for comments from Maurice and Rosy. They had no real objections except for wanting us to mention that Fraser in their lab had considered hydrogen-bonded bases prior to our work. His schemes until then unknown to us in detail, always dealt with groups of three bases, hydrogen-bonded in thy middle, many of which we now knew to be in the wrong tautomeric forms. Thus his idea did not seem worth resurrecting only to be quickly buried. However, when Maurice sounded upset at our objection, we added the necessary reference. Both Rosy's and Maurice's papers covered roughly the same ground and in each case interpreted their results in terms of the base pairs. For a while Francis wanted to expand our note to write at length about the biological implications. But finally he saw the point to a short remark and composed the sentence: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
Sir Lawrence was shown the paper in its nearly final form. After suggesting a minor stylistic alteration, he enthusiastically expressed his willingness to post it to Nature with a strong covering letter. The solution to the structure was bringing genuine happiness to Bragg. That the result came out of the Cavendish and not Pasadena was obviously a factor. More important was the unexpectedly marvelous nature of the answer, and the fact that the X-ray method he had developed forty years before was at the heart of a profound insight into the nature of life itself. The final version was ready to be typed on the last weekend of March. Our Cavendish typist was not on hand, and the brief job was given to my sister. There was no problem persuading her to spend a Saturday afternoon this way, for we told her that she was participating in perhaps the most famous event in biology since Darwin's book. Francis and I stood over her as she typed the ninehundred-word article that began, "We wish to suggest a structure for the salt of deoxyribose nucleic acid (DNA). This structure has novel features which are of considerable biological interest." On Tuesday the manuscript was sent up to Bragg's office and on Wednesday, Apri12, went off to the editors of Nature.
Linus arrived in Cambridge on Friday night. On his way to Brussels for the Solvay meeting, he stopped off both to see Peter and to look at the model. Unthinkingly Peter arranged for him to stay 'at Pop's. Soon we found that he would have preferred a hotel. The presence of foreign girls at breakfast did not compensate for the lack of hot water in his room. Saturday morning Peter brought him into the office, where, after greeting Jerry with Cal Tech news, he set about examining the model. Though he still wanted to see the quantitative measurements of the King's lab, we supported our argument by showing him a copy of Rosy's original B photograph. All the right cards were in our hands and so, gracefully, he gave his opinion that we had the answer. Bragg then came in to get Linus so that he could take him and Peter to his house for lunch. That night both Paulings, together with Elizabeth and me, had dinner with the Cricks at Portugal Place. Francis, perhaps because of Linus' presence, was mildly muted and let Linus be charming to my sister and Odile. Though we drank a fair amount of Burgundy, the conversation never got animated and I felt that Pauling would rather talk to me, clearly an unfinished member of the younger generation, than to Francis. The talk did not last long, since Linus, still on California time, was becoming tired, and the party was over at midnight.
E1izabeth and I flew off the following afternoon to Paris, where Peter would join us the next day. Ten days hence she was sailing to the States on her way to Japan to marry an American she had known in college. These were to be our last days together, at least in the carefree spirit that had marked our escape from the Middle West and the American culture it was so easy to be ambivalent about. Monday morning we went over to the Faubourg St. Honoré for our last look at its elegance. There, peering in at a shop full of sleek umbrellas, I realized one should be her wedding present and we quickly had it. Afterwards she searched out a friend for tea while I walked back across the Seine to our hotel near the Palis du Luxembourg. Later that night with Peter we would celebrate my birthday. But now I was alone, looking at the longhaired girls near St. Germain des Prés and knowing they were not for me. I was twenty-five and too old to be unusual.
 |
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EPILOGUE
VIRTUALLY everybody mentioned in this book is alive and intellectually active. Herman Kalckar has come to this country as professor of biochemistry at Harvard Medical School, while John Kendrew and Max Perutz both have remained in Cambridge, where they continue their X-ray work on proteins, for which they received the Nobel Prize in Chemistry in 1962. Sir Lawrence Bragg retained his enthusiastic interest in protein structure when he moved in 1954 to London to become director of the Royal Institution. Hugh Huxley, after spending several years in London, is back in Cambridge doing work on the mechanism of muscle contraction. Francis Crick, after a year in Brooklyn, returned to Cambridge to work on the nature and operation of the genetic code, a field of which he has been the acknowledged world leader for the past decade. Maurice Wilkins' work remained centered on DNA for some years until he and his collaborators established beyond any doubt that the essential features of the double helix were correct. After then making an important contribution to the structure of ribonucleic acid, he has changed the direction of his research to the organization and operation of nervous systems. Peter Pauling now lives in London, teaching chemistry at University College. His father, recently retired from active teaching at Cal Tech, at present concentrates his scientific activity both on the structure of the atomic nucleus and on theoretical structural chemistry. My sister, after being many years in the Orient, lives with her publisher husband and three children in Washington.
All of these people, should they desire, can indicate events and details they remember differently. But there is one unfortunate exception. In 1958, Rosalind Franklin died at the early age of thirty-seven. Since my initial impressions of her, both scientific and personal (as recorded in the early pages of this book), were often wrong, I want to say something here about her achievements. The X-ray work she did at King's is increasingly regarded as superb. The sorting out of the A and B forms, by itse1f, would have made her reputation; even better was her 1952 demonstration, using Patterson superposition methods, that the phosphate groups must be on the outside of the DNA molecule. Later, when she moved to Bemal's lab, she took up work on tobacco mosaic virus and quickly extended our qualitative ideas about helical construction into a precise quantitative picture, definitely establishing the essential helical parameters and locating the ribonucleic chain halfway out from the central axis.
Because I was then teaching in the States, I did not see her as often as did Francis, to whom she frequently came for advice or when she had done something very pretty, to be sure he agreed with her reasoning. By then all traces of our early bickering were forgotten, and we both came to appreciate greatly her personal honesty and generosity, realizing years too late the struggles that the intelligent woman faces to be accepted by a scientific world which often regards women as mere diversions from serious thinking. Rosalind's exemplary courage and integrity were apparent to all when, knowing she was mortally ill, she did not complain but continued working on a high level until a few weeks before her death.
THE END
__________________________________
__________________________________
 |
| 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.
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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