Chapter 22 17 Triple Helix-2

The problem is to show how to place the phosphoric acid in the center, while the normal pH is generally considered to be negatively charged.These negative charges at the core repel each other, and the structure explodes.Although the triple helix they conceived looked very elegant and matched the relevant data so well, Crick and Watson figured that there must be a place in the core where positive ions could offset the negative charges.They found a copy of "The Nature of the Chemical Bond" to see if there were any inorganic ions that met their needs.They found that both manganese and calcium met the requirements.There is no evidence that positive ions of these two elements exist, however there is no evidence that they do not exist either.After all, they were thinking carefully after Pauling, as Pauling must have done in this case: first imagine the structure, and then consider some minor details.

The two young men felt very proud of having overcome this difficult problem so quickly.They invited Wilkins and Franklin to Cavendish to watch their victories.Franklin tore the invitation letter into pieces.The problem was not only that the molecules were assumed to be helical—Franklin never believed that the X-ray data would prove it—but that they could have imagined positive ions condensing together in the center of the helix.She pointed out that in the nucleus, manganese or other ions are undoubtedly surrounded by water molecules and are therefore neutral, making it impossible to bind phosphoric acid together.Besides, water is very important.Franklin also pointed out that Crick and Watson must have got some data wrong.In her view, DNA is a very thirsty molecule, with 10 times more water in it than their models allow.From the ability of this molecule to absorb water, she saw that phosphoric acid should be located on the outside of the molecule and accumulated in a thin water layer.The water capacity is not stable, indicating that the density calculated by Crick and Watson is not accurate.

As it turned out, Franklin was right.The two young men tried to persuade Wilkins and Franklin to cooperate with them in another experiment, but they pushed back.News of this failure reached the ears of Bragg, who quickly transferred Crick back to the protein group and Watson to something more commensurate with his knowledge base, namely the tobacco mosaic disease. Viruses were subjected to crystallography studies. However, the two men, especially Watson, did not stop thinking about nucleic acids.In Pauling's memory, Watson was enthusiastic about DNA "literally to the point of madness", and there was no way to stop there on this issue.He and Crick began to conduct secret research in secret, choosing to talk quietly in the office or a local bar.The models they got might not be right, but they were sure their research methods were right.Perhaps, all they need is a little more chemistry. On Christmas 1951, Crick gave Watson a copy of "The Nature of the Chemical Bond". "Somewhere in this classic Pauling book," Watson recalled, "I hoped to find the real secret."

coiled coil After Pauling attended several meetings in France, he hurried to England, hoping to make up for the time lost due to the passport turmoil. In Lu Yue in 1952, he visited several protein research centers in the UK, exchanged views with some of his critics, and answered their questions.At this time, people have found some new evidence, further showing that the alpha helix is ​​an important building block of many kinds of natural proteins, including globulins.In addition, the lamellar structure was also confirmed.Pauling believed that the theory of the alpha helix had been proven, so he began to turn his attention to some new ideas about how his structure could bend around the corner and fold onto itself, making the globulin into a tightly packed spherical.He found that the British were also receptive to his alpha spiral because they had evidence of it from their own research. "In this way, I think, I have redeemed myself for not being able to attend the meeting of the Royal Society in May—anyway, for myself, some of these people have made it clear to my face that expressed their skepticism about the correctness of the protein structure we conceived," Pauling wrote to Arnie Tesselles.Clearly expressed doubts can be given clear answers.On some issues, Pauling tried his best to make further arguments to the British; on other issues, he also revised and perfected his own ideas.

During his visit to Cavendish, Pauling met many young scholars, especially the meeting with Crick, which made him very happy.Since being transferred away from the DNA research topic, Crick has spent most of his time working on a research project.The project, started by the Prague team after reading Pauling's protein paper, aimed to find a mathematical formula to predict the way helices would diffract X-rays. In the spring of 1952, Crick and two colleagues published a paper providing the exact steps that should be followed for the mathematical processing.This was Crick's first important scientific achievement, which later proved to be very useful.Before publishing the paper, he proudly sent Pauling a copy.Next, he began to think about how to use this formula to explain the reflection data of 5.1 Angstroms, which is also a gap that Pauling's alpha spiral theory did not touch.

Crick hopes to do postdoctoral research at Caltech.He casually raised the possibility of such a possibility while driving around Cambridge in a limousine with Pauling.At this moment, Crick, who has always been eloquent, stuttered suddenly.He was full of thoughts and mixed emotions, half of which was awe—here, an ordinary graduate student, sitting next to what he believed to be the most famous scientist in the world—and the other half was terror. DNA is not the right topic; after all, he has been considered unsuitable for research in this area, however, he has created a new theory that can be used to explain why Pauling's alpha helix does not get 5.1 Angstroms reflectance data, which can be observed in most natural substances.He knew that Pauling was also thinking about this issue, so he didn't want to reveal too much to the guests.On the other hand, however, he very much wanted to make a good impression on his guests.In fact, he didn't need to worry so much. Pauling had already focused on Crick.Pauling offered to invite him to work with him at Caltech for a year.Crick felt more confident in himself, and asked, "Have you ever thought about the possibility that each alpha helix could be coiled together?" possible scenarios, several of which involve the assumption that individual helices are intertwined.He remembers answering, "Yes, I thought about it," before avoiding the subject.It occurred to him that he was almost ready to publish the idea, and therefore he did not intend to share it with a student of Cavendish, promising though he was.

However, according to Crick, Pauling did not give the impression that he had spent some time studying this problem. Protein remained a priority in Pauling's mind.During his month in the UK, he rarely thought about DNA, and didn't even bother to visit Kings College to see the increasingly expensive X-rays taken by Wilkins and Franklin.He later recalled that there were two reasons for this: one was that he was preoccupied with protein, and the other was that he still believed that Wilkins would not let him share the information. This is a historic mistake.Franklin had already taken pictures of the layers in the wet, pure stretch of the DNA.On the one hand, the figures clearly show double symmetry - which rules out the possibility of a triple-stranded structure; on the other hand, a helical cross-like reflected streak can be seen from the figures.If only Pauling could have seen the photos—he has no reason to think that Franklin must keep him from seeing them; in fact, she had already briefed Corey on this aspect of her life when he visited in May. Franklin's work--if Pauling could have had a talk with Franklin, she would not have been shy about her own firmly held views on the subject of water content and its effect on molecular form.If Pauling had heard her thinking in overthrowing the Crick-Watson model, he would undoubtedly have substantially changed his subsequent research methods.To put it mildly, if Pauling visited Franklin, he would at least get the impression that Astberry's earlier photograph, the one he is using, shows a mixture of the two molecular forms .

Historians speculate that the refusal of Pauling's passport to the Royal Society meeting was a key event in Pauling's inability to discover the structure of DNA.Had he been at that meeting, he would have seen Franklin's work, and would have had a better chance of winning again on the right track.This view strongly supports the conclusion that officials should not interfere with normal academic exchanges among scholars.The real problem, though, cannot be blamed on policies around passports.In fact, three factors conspired to lead Pauling in the wrong direction.The first factor was that he focused entirely on protein structure, ignoring almost all other aspects of the problem.The second factor is that he lacks sufficient data. The X-ray pictures he has been using are of a mixture of the two forms of DNA, which are of little value.The third factor is that he is too conceited, and he never thought that DNA needs his all-out research.After talking with Perutz and Bragg, he seems to have learned that Crick and Watson once showed their skills on the problem of DNA structure, but failed; he also knew that Wilkins was painstakingly studying This one question.However, he believes that these people may not be his competitors.Yeah, how are they capable of competing with him?Many facts have proved that he is the only person in the world who can solve the problems of large biomolecules.

"I kept thinking that sooner or later I would find the structure of DNA," Pauling said. "It's just a matter of time." Pauling missed an opportunity to view Franklin's photograph and returned to Caltech in September.He immediately returned to research work, with a view to finally completing the study of higher-level spiral structures. "The study of protein structure has now entered a very exciting phase," he wrote. "It's hard for me not to spend all my time on this problem, and I can't take care of other things." He found a way to make the alpha spiral itself twist, like a strand of yarn wrapped around As on a finger, it forms the coiled coil that Crick mentioned, and this form can show X-ray reflections that cannot be seen by the alpha helix itself.Next, he went a step further by imagining how these coiled coils could be wound around each other, thus forming cords with varying numbers of strands.He published these new ideas in October.

Before that, however, Crick had learned about these ideas through Pauling's son Peter.Peter arrived in Cambridge in the autumn of 1952 as a graduate student in Kendrew's laboratory.He was only 21 years old that year, lively and playful.He soon fell in love with Erna, Perutz's "mutual barnyard" girl, but he didn't take his research on the structure of myoglobin so seriously-"a bit wild," this is Crick's evaluation of him.Peter soon became intimate with Crick and Watson, and their new office mate, Jerry Donohu.Donohu, who also immigrated from Caltech, had worked for Pauling for several years before winning a Guggenheim fellowship and coming here in the fall.

Their offices became a center for informal scholarly exchanges between Cambridge and Pasadena.Both Peter and Donoghue corresponded with Pauling, so the conversation in the office was also, for Crick and Watson, a source of at least a glimmer of what Pauling wanted to do.Pauling, for example, wrote to his son that he was seriously exploring the structure of natural keratin, a substance also made of strands of intertwined helices.When Peter told this to Crick, the first thought in Crick's mind was that Pauling had plagiarized his own inadvertent thoughts when he and Pauling were riding together.Crick immediately regrouped and began a new endeavor.After several months, he finally solved the last few mathematical difficulties. On October 22, he sent a brief note to Nature outlining his thoughts.The editorial office of the journal received this note just a few days after Pauling received a longer manuscript on the same subject. However, Crick included a note on the cover of the short article, calling for the prompt publication of his article.In general, annotations are published faster than long papers, so Crick's annotations were published much earlier than Pauling's papers.Over the course of several weeks, a row broke out on both sides of the Atlantic, with both parties claiming to be the originators.Later, the Cavendish researchers conceded, admitting that Pauling's set of ideas went far deeper than Crick's.As for Pauling, he was not surprised to see Crick's short article in print, but was a little annoyed, blaming Nature for not publishing both articles at the same time.In the end, the two parties reached a gentleman's agreement, acknowledging that the two individuals independently arrived at the same result. This is just a small episode.Significantly, the last major hurdle to the recognition of the alpha spiral has finally been cleared.By late autumn, Pauling had become convinced that his structure, with its various arrangements of coiled coils, was equally applicable to the basic substances in hair, horn and nails.He also gained new insight into feather structure.Evidence for the presence of alpha helices in many globulins is also accumulating.By late November, Pauling felt that his belief in the alpha helix, which had been shown to be the main structure of hemoglobin, serum albumin, insulin, pepsin, lysozyme, and a dozen other globulins, was fully confirmed. Morphology, he happily wrote to a colleague: "In fact, it has now been found that all globulins studied have the alpha helix as the dominant form of their structure." beautiful structure At this point, however, the alpha spiral is no longer the astonishing discovery it was once thought to be.This is a breakthrough in methodology, a test of Pauling's randomized research method, and an important part of a series of major achievements.However, as Pauling said, in the final analysis, the alpha spiral is just "a structural form".It seems that this is a stable sorting method, and by means of this method, the structure of the polypeptide chain can be imagined.Molecular biologist Gunther Sdent later said: "No matter how great Pauling's work was, the discovery of the alpha helix did not immediately lead to many new concepts about proteins, such as how proteins work. What is it made of, and so on. This discovery does not seem to lead people to many novel experiments, nor does it leave a wide space for people's imagination." At this time, Pauling already understood in his heart that the real harvest, or in other words, the real mystery of life lies in DNA.It was this question that became the focus of his next consideration. On November 25, 1952, three months after returning from England, Pauling attended a seminar on biology held by Caltech.The lecturer was Berkeley professor Robly Williams, who did some amazing things with the electron microscope.For example, he uses a sophisticated technique that allows him to photograph extremely small biological structures.This fascinated Pauling.A pattern of long, twisted chains of sodium ribonucleic acid can be seen in a photograph taken by William.This is a salt in the form of a nucleic acid, the shaded area showing the three-dimensional details.What caught Pauling's special attention was that these chains clearly took on the shape of a cylinder: they were not planar ribbon structures, but long, thin tubes.In the shaded classroom of the seminar class, Pauling looked at the slides and guessed that DNA might also be a helix, because other ideas not only did not fit with Astberry's molecular X-ray diagrams, but also with his own. The photos I see now don't match either.Even better, Williams was even able to estimate the size of the structure from his photographs, and he calculated that each strand was about 15 angstroms in diameter.Pauling was very interested in this and asked William to restate this figure.William confirmed the correctness of the data, but also explained the difficulty he encountered in obtaining this precise figure.The molecule William showed was not yet DNA, but a close relative of a molecule—which prompted Pauling to ponder. The next day, Pauling sat at his desk, holding a pencil and a slide rule, and a pad of writing paper on the desk.Based on new data obtained that summer from Alexander Todd's laboratory, it was possible to determine the location of the junctions between sugars and phosphates in DNA; other work showed where they were attached to the bases.Based on his previous research, Pauling believed that the bases of different sizes must be located on the outside of the molecule, and the phosphates were on the inside of the molecule.He now knew that the molecule was likely to be helical.These conclusions were the starting point for his initial observations on DNA.This is his first attempt to study the structure of DNA, and he has not yet grasped how far he can go. One of the special reasons is that he still lacks a clear understanding of the precise size of the DNA base-sugar-phosphate structure and the size of the casting angle. Unmistakable stats, but worth a look. In order to determine the molecular weight and the expected value of the axial distance of each cycle section, Pauling quickly carried out some related calculations.Astberg's photographs show strong reflections every 3.4 angstroms—according to Pauling's calculations, this is about three times the size he estimated for a fragment of nucleic acid in the direction of the fiber.It is very unlikely that three different nucleic acids form a looping group; the triple-stranded structure seems to explain the phenomenon of continuous looping more easily.He calculated the density and showed that if there are three chains, they must be tightly packed together to match the observed molecular weight data.Still, it's possible.On the first page Pauling used to study DNA, he made a total of five lines of simple calculations, and he wrote: "Maybe what we get is a three-stranded structure." Immediately afterwards, he was hooked on the idea that the three chains were intertwined, with the phosphoric acid in the center.As he sketched and calculated, he soon discovered that doing so, along the direction of the fiber, would not allow the formation of hydrogen bonds to hold the intertwined chains in place, as the alpha helix would.If there are no hydrogen bonds, what holds the shape of the molecule?He saw that there was one place where hydrogen bonds could form, and that was through the center of the molecule, from phosphoric acid to phosphoric acid.It's an unexpected thought, but there are other things that seem to need to be figured out.After Pauling made six full pages of calculations, he wrote: "Note that there are about 3 residues for each chain turning around, a total of 3 chains are closely intertwined with each other, and between each Po4 is H-bonded." The only problem was that there didn't seem to be enough room in the center of the molecule, where the phosphates were packed close together.That night, he had to put down the pencil in his hand. Three days later, he returned to this question.According to Astberg's data, DNA is a relatively compact molecule, so the central part is tightly packed.Trying to squeeze all the phosphoric acid in the three chains into the narrow space determined by Astbury is like trying to force the feet of Cinderella's step sister into one of Cinderella's glass dancing shoes in fairy tales Same, it can't be done anyway. "Why are Po4 arranged in columns squeezed so tightly together?" he wrote in despair.If Astberry's estimate of the distance had been amplified a bit, everything would have been fine.However, Pauling can't do this, because he can't deviate too much from Astbury's data.Later, Pauling tried to deform the phosphoric acid tetrahedron a little bit, making some sides shorter and the other sides longer, and then see if it fits.Looks like things are a little better, but still can't do it.Pauling had to stop again. Next, Pauling ordered an assistant to go to the reference room of the Department of Chemistry to check the relevant literature, as long as it was the X-ray crystal diffraction data of nucleic acid, all the data were collected.Apart from the work of Astberg and the Norwegian crystallographer Sven Forberg, there is not much to refer to.Sven Furberg, who had worked under Bernal's supervision, had discovered that the bases in DNA are oriented perpendicular to the sugars.No sources detail the structure of purines or pyrimidines, let alone nucleic acids. On December 2, Pauling once again launched an impact on this subject.Nine full pages are full of graphs and calculations.He thought hard, and got something that seemed possible. “I squeezed the phosphoric acid together as much as I could and deformed them as much as I could,” he wrote on a scratch paper.Although the oxygens in some phosphoric acids are very close together in the center of the molecule and are not so loose between each other, the way they fit together is unassailable.In addition, Pauling also saw that the oxygen in the middle squeezed together to form an almost perfect octahedral shape, one of the most basic configurations in crystallography.Its construction is extremely compact, and the parts are arranged in perfect order, so the structure must be correct.It was less than a week since he first sat down to study the problem. The next day, Pauling excitedly wrote to a colleague: "I now think that we have found a complete structure for nucleic acid molecules." From the second-floor office of Lehring's lab to Shoemaker's office. "He was emotional," Shoemaker recalls.Pauling couldn't wait to introduce his thoughts to the young man, talking about his ideas at the top of his voice, while constantly checking and revising his model.He began collaborating with Corey, aiming to characterize this fine structure in detail. However, trouble came again.Corey's careful calculations of the positions of the atoms showed that the oxygen at the center was actually too close together to fit together. In early December, Pauling resumed twisting and squeezing the phosphate octahedron.He was asked how, using his model, he could create a sodium salt of DNA in which the positively charged sodium ions were attached to the negatively charged phosphoric acid as envisaged.There's no room for sodium salt in this tightly packed core of his, is there?Pauling had to admit that he couldn't find a proper way to house the ions, but he'd figure it out more clearly later.In addition to this point, other results should be affirmed.Using Crick's mathematical formula to calculate the proposed structure, it can be shown that his spiral model is consistent with most X-ray data.Of course, not all data fit the bill.Shoemaker also tried some models independently, and also found a way to distort the phosphate polyhedron so that the phosphates were less crowded, but Pauling couldn't see a reason to change his mind for a while.Phosphates at the core come together seamlessly, it's impossible not to be right. In Pauling's mind, the central problem boiled down essentially to one that involved the structural chemistry of phosphoric acid.The biological significance of DNA would be clarified later, he thought; if the structure was correct, the biological importance would manifest itself in some way.At this point, his task was to figure out the structure, not its function.He therefore did not consider the specific situation in the larger vicinity of the molecule, but concentrated all his thoughts on one thing: finding a way to place those phosphoric acids in the center of the molecule, and to ensure that the resulting helical fit the existing data. He had succeeded with the alpha spiral problem, so he was convinced that his research method was correct.He had built protein helices using rigorous chemical principles, published this result in the face of contradictory data, and only later found the facts he needed to answer his critics.Now, he also believes that he has the ability to rush ahead of such people, using his deep skills in chemistry to pick a structure that is intuitively correct.If you want to wait patiently until every mystery is solved, you can never expect any discoveries you make to be acknowledged.Moreover, he felt that the triple helix he had conceived was correct. A week before Christmas, he wrote Todd at Cambridge, saying: "We believe that we have discovered the structure of nucleic acid. In fact, I am convinced that ... it is a very beautiful structure." Pauling knew, Todd was working on a purified nucleic acid, so he asked Todd to send him some samples for X-ray analysis.Both Dr. Corey and myself are deeply disturbed that there has not been a report that anyone has accurately determined the structure of any nucleotide.We have recognized the need for some structure determination work in our laboratory.I know that the Cavendish scholars are working on this, but it's a huge field and we can't expect them to cover everything. Pauling then wrote to his son Peter, and to Donohu, saying that he hoped to finish a short paper on nucleic acids soon. However, this structure is still not correct enough.Corey made a series of calculations again and found that the phosphoric acid squeezed each other too much, and the corresponding atoms were too close to each other, so it was unreasonable.Pauling intends to make some adjustments and repairs to this structure. Some places need to be changed, and some places must be suppressed to try to get closer to the answer, but it is still not perfect. While Pauling was struggling with the structure of DNA, another disturbing thing happened. On December 23, Budenz, a full-time agent of the FBI and a confidant of the Congressional Investigation Committee, publicly testified at a special committee meeting of the House of Representatives investigating charitable foundations, saying that Pauling, as a member of the Guggenheim Foundation Advisory Committee, One member is an undisclosed Communist Party member.Budenzi was also afraid that people would say that he was not working hard enough, so he actually revealed the names of the original 23 guarantors and 3 officials from various groups.These people, like Pauling, had nothing to do with communism.Budenz's testimony will naturally irritate many prominent figures with close ties to some powerful foundations, and will eventually fuel a backlash against McCarthyism.But, in the short term, the timing of the announcement—two days before St. Yen, when the news media is struggling with the lack of reporters to follow up and find sensational front-page headlines—these are Those named will have little chance of rebutting, so they are especially hurt. For the most part, Pauling has followed the decision he made a year ago and has not been active in politics.At this moment, he felt as uncomfortable as being bitten by a poisonous snake.He responded straightforwardly in his typical fashion. "That's a complete lie," he told the news outlet. "If Budenz is not convicted of perjury, then we must be able to draw the conclusion that the courts and many investigative committees in Congress have no intention of knowing and publishing the truth of the facts." Later, Pauling found that Budenz could not be charged with perjury. He was punished by law because his testimony was protected by congressional privilege.So he tried another way to bring his informant to court, calling Budenz in the newspapers an "expert liar" in the hope that Budenz would denounce him instead.But Budenz didn't take the bait. Pauling was quite surprised by the political attack this time, and was very depressed.He took the unusual step of inviting several colleagues to his lab on Christmas Day to see what he was doing with DNA.He was very tired of the minutiae problems with his models, and he only wanted to hear good things from people.The few visitors who listened to Pauling's briefings enthusiastically praised his ideas and lifted his spirits.During the last week of the year, he and Corey put the finishing touches on the manuscript. On the last day of December 1952, Pauling and Corey posted their paper, "A Structure Conceived for Nucleic Acids," to the Proceedings of the National Academy of Sciences.They emphasize in the paper that this is "the first precisely described nucleic acid structure that researchers have proposed so far"—thus putting their work on nucleic acids on a par with that on alpha helices.The thesis expounds the structure of the core part of the molecule in detail, and spends most of the space discussing how to construct the phosphate polyhedron accurately, and of course also introduces some biological mechanisms.In Pauling's model, the bases are the information-carrying parts of the nucleic acid. They are stretched out, just like the branches and leaves on a tree, leaving enough space between each other and can be arranged in any way. Thereby ensuring that the molecule can have various changes, and the information contained will also have various specific contents.Prior to this, Astberg had noticed that the nucleic acid helical pitch is 3.4 angstroms, which is almost equal to the distance between each amino acid in the stretching direction of the polypeptide chain.This inspired us to consider that new proteins might be cut directly from a nuclease.Pauling saw that the same thing was allowed to happen in his model, the gaps formed by the sides of four adjacent bases in the direction of the chain would fit exactly one amino acid. In this paper, however, the authors use a rare, tentative language, contrary to usual. "This is a very promising structure," writes Pauling, but also "an unusually compact structure"; The comparison of the theoretical values ​​calculated by the formula can only be regarded as "unsatisfactory results". He continued to write that the position of each atom "probably can be described more precisely". As it turns out, the paper was written in a bit of a hurry.Pauling knew that DNA was important, and he knew that Wilkins and Franklin were keen on the subject, and that the team in Prague had tried it at least once.He also recognized that this was a simpler structure compared to proteins.And, he knows full well, whoever gets a structure roughly right first—even if the details are a little buggy—has established the lead.This is exactly what he dreamed of.What is said first, not last, on the DNA issue, the first to be published, will be cited by those who come later.This does not require 100% accuracy.How he wanted to gain the reputation of being the first discoverer! In order to make sense of this hastily put together treatise on nucleic acids, it is best to compare it with Pauling's work on proteins.Pauling's alpha spiral is the result of his analysis over and over for more than ten years, in which he has condensed his painstaking efforts in crystal diffraction research for tens of thousands of hours.Before he formally published his model, his lab determined the individual components of amino acids to a fraction of a degree, or hundredth of an Angstrom.On the subject of protein, there is a large amount of clear data taken by X-rays, which allows Pauling to do careful research and makes it possible for him to eliminate dozens of different structures.From the rough idea of ​​the alpha spiral in his mind to his actual publication of this structure, it took a total of two years.During this time, he and Corey spent much of the time together, and together the two produced a series of delicate 3D models, which they reviewed and revised over and over again. 对于DNA，这些事都没有做。 “我仅有的疑点是……” 12月底，克里克和沃森从彼得口中得知，鲍林已经解决了DNA问题，心里感到很不是滋味。说不清楚到底是绝望，还是不服气——两个人一会儿估摸着鲍林是怎样打败他们的，一会儿又确信，鲍林没有看到过威尔金斯和富兰克林的Ｘ光照片，他不可能超过他们。当然，他们又想到，他毕竟是鲍林，因此没有什么事一定办不到——两个人又继续研究自己的问题了。要是他们能够在鲍林发表论文之前就能独立地搞出点名堂，也许他们至少可以分享一部分荣誉。 那一年春天，就是克里克和沃森两人受到警告不得搞DNA研究以后几个月，也是在鲍林来访卡文迪什前的几个月，有人介绍他们认识了切加夫。切加夫是一位出牛于奥地利的牛物化学家，为人尖刻，固执已见，他曾经使用色谱分析法研究过核酸的化学成分。他对克里克和沃森两人的印象并不好。“我从来就没有碰到过这么无知而又狂妄的两个人，”他说道。“他们对我说要制作一个螺旋，也就是一个多核苷酸，以便与鲍林的阿尔法螺旋竞争。他们喋喋不休地谈论有关'螺距'的情况，以至于我还记得我随后写下了这样的话：'两个小贩寻找着一个螺旋'”①不过，他们这一次交谈对于克里克和沃森来说，还是意义重大的。切加夫告诉他们，在DNA中，不同碱基出现的可能性之间，存在着一个简单的关系，就是腺嘌呤和胸腺嘧啶出现的数量大致上相同，鸟嘌呤和胞嘧啶出现的数量也大致相等。每一对碱基中，较大的一个是嘌呤，较小的一个是嘧啶。切加夫在1947年在大西洋彼岸旅行期间，曾对鲍林讲起过这一种关系，但鲍林并没有在意。 ①英语中，“pitch”一词兼有“螺距”和“摊位”之意，但“pitchman”却只能作“小贩”或“推销员”解。在此，说话人故意用pitchman一词来嘲弄克里克和沃森。 但是，对于克里克和沃森来说，这可大不一样了。富兰克林的批评已经促使他们将磷酸放到了分子的外侧；现在他们又受到启发，得知内侧各对碱基之间存在着一一对应的关系。他们开始设想，在螺旋中，嘌呤和嘧啶以某种方式挨次排列在分子中心的下部。 1953年2月初，他们通过彼得看到了鲍林寄来的关于DNA的论文手稿，这是两位学者求之不得的东西。使他们大吃一惊的是，鲍林的模型看上去与他们早先舍弃的三链结构很相似，只是各个部件装配得更加紧密一些罢了。只要将手稿读上几分钟，就不难明白，在分子中心并没有地方可以放置用来维系带负电的磷酸所需的正离子。克里克和沃森两人几乎惊呆了。鲍林的结构离不开磷酸之间的氢键，但是，DNA中的磷在正常的洲中失去氢时，怎能再会有氢呢？“没有氢原子，整个链就会马上散飞掉，”沃森说道。虽然他们以前用自己的模型说明了这一点，但他们还是重新核对了一遍。没有错，在他们十分珍视的教科书上，白纸黑字，写得明明白白：磷酸必定处于离子的状态。他们参阅的就是鲍林编着的《普通化学》教科书。 他们感到莫大的安慰。“要是一名学生犯了一个类似的错误，他一定会被人认为不配在加州理工学院化学系读书，”沃森后来这样说。他和克里克毫不迟疑地向剑桥大学的化学家反映了他们批评的意见。当天傍晚，鲍林的错误就在全校沸沸扬扬地传开了：莱纳斯的化学出了毛病。 对于沃森来说，这倒是一个重要的时刻。他向威尔金斯讲述了鲍林的错误，同时也介绍了自己关于DNA呈螺旋状的想法。他得到了回报：他第一次被给予机会察看富兰克林拍摄到的有关DNA分子的最新照片。富兰克林已经发现，DNA存在着两种形式：一种处于缩合干燥的状态，另一种处于扩张湿润的状态。鲍林先前使用的阿斯特贝里拍到的照片，显示出来的是这两种形式的混合品；而富兰克林的新照片则要清晰得多，而且纯粹是其扩张的形式。沃森由此马上认定，这种分子是一个螺旋，他还从中得到了解决问题所需的几个主要的参数。 克里克尽管仍耿耿于怀那次盘绕螺旋的事，此时心情却显得格外舒畅。他致函鲍林，谢谢他事先就给了他关于核酸的这篇论文的单印本。“我们为其结构之巧妙折服了，”他写道。“我仅有的疑点是，我还想不出怎样把它装配好。” 鲍林这次明显的失误也使布拉格很得意，他同意让克里克和沃森全部身心地重新投入DNA的研究，在这里，一扇机遇的窗口打开了，布拉格想让卡文迪什赶在鲍林卷土重来前抢占这一个高地。 然而，鲍林却转向了一个新项目，那就是开春以来一直在研究的铁磁性理论。与此同时，他还开始筹划秋季在加州理工学院召开一次重要的研究蛋白质问题的国际性会议。只是在彼得2月中旬写信告诉他，英国人对他提出的结构是嘘声一片时，他才不得不回过头来再次考虑DNA。此时，科里最后一次校校了鲍林的原子坐标，其中有些数据仍然表明结构太紧密，不合理。“我对核酸的结构又验算了一次，旨在修饰一下有关的参数，”鲍林回信给彼得道。“我听到有人说，沃森和克里克在早先一些时候就已经构造出这一种结构，但他们没有将这件事做下去，也许这是一次言过其实的误传吧。”2月下旬，他终于采纳了舒梅克的一个意见，将各个磷酸组扭曲了45度，发现结构中存在的应力已有所减小。 仍然有不妥的地方。鲍林在加州理工学院的一次讨论班上介绍了他的DNA结构，听众的反应很冷淡；此后，德尔布吕克对舒梅克说，他认为鲍林的摸型是不能令人信服的。他还提到了沃森给他写来的一封信，信中称，鲍林的结构包含了“某些非常严重的错误”。沃森在信中补充说，“我已找到了一个非常漂亮的模型，其精美的程度使我很吃惊，这是以前谁也没有想到过的事。”鲍林希望了解更多的情况，他很快就写信给沃森，邀请他来参加定于秋天举行的蛋白质研讨会。鲍林在信中提到，他已从德尔布吕克处得知他正在研究DNA，因此鼓励他把这一课题做下去。“科里教授和我都认为，我们的结构尚未证明是正确的，”他写道，“不过，我们倾向于认为它是正确的。”3月初，他与爱娃·海伦一起驱车前往加州大学里弗赛德分校，目的是检验一下那里收集到的一组有机磷酸，结果找到了一些可以用于结构分析的材料。这些材料与DNA中的磷酸相似。他还要寻找一些模型，从中了解他那些多面体到底可以变到怎样的程度。克里克讽刺他怎样去维系分子时所用的尖刻语言，促使他收集了一些化学研究的先例，说明在同一分子中相邻离子同带负电荷的现象是存在的。此外，他自己也得找一些理由，说明DNA中心也许有一种特殊的环境，容许磷酸像他提议的那样存在着。对鲍林来说，这仍然关系到磷酸的化学特性。与此同时有人给他寄来了所需要的核苷酸样本。鲍林开始对其作Ｘ射线分析。 他最终在为寻找一种合理的结果做奠基性工作。可惜，这一切都为时已晚。 克里克得谢谢鲍林的论文，他终于得到指示重返DNA的研究工作。克里克和沃森两个人各自都拼命地设想了各种各样不同的模型，不过，此时的注意力已集中在双链模型上，因为切加夫曾经提醒他们考虑碱基双双成对的情况。沃森在给德尔布吕克的信中提到的“非常漂亮的模型”就是其中的一次尝试，但是，正如多诺胡指出的那样，那个模型是不对的。 多诺胡发表的看法后来证明是一个关键。作为达特默思大学毕业的高材生，多诺胡从40年代开始就曾长期在加州理工学院跟随鲍林工作和学习，因此，他对结构化学可谓是了如指掌。氢键曾是他专门研究的课题，因此他心里很清楚，克里克和沃森在化学上还只能算初出茅庐的新手，他们两人为鸟嘌呤和胸腺嘧啶摆弄出来的结果是错误的。多诺胡帮助他们明确了方向，将中心氢键上的氢原子放置在合适的位置上，推翻了他们原先设想的模型，促使他们走上了正确地解决问题的轨道。 克里克和沃森经过多诺胡的指点，开始认识到各对具体的嘌呤和嘧啶之间是由氢键自由地连接起来的：腺嘌呤连接胸腺嘧啶，鸟嘌呤连接胞嘧啶。这是最后的一道谜底，其结果闪耀着夺目的光彩。将一个大碱基与一个小碱基配对，不但使整个结构的骨架处于平稳的状态，而且为切加夫的发现提供了一种简单的解释。由此得到的结构犹如一架楼梯，各对碱基就是上面的一步步台阶，糖一磷酸骨架是框架，两者结合在一起，就能方便地形成符合Ｘ射线资料的螺旋。 这一种结构不但看上去很美观，而且其含意也非常丰富。两条链互为补充，每条链都是另一条链的镜像反射；将两者分开，每条链就可以作为形成一个新螺旋的基础，这个新螺旋与原来的螺旋完全相同。由此可以立即得到有关DNA复杂的思想，这是鲍林的模型无法做到的，因为在他的模型中，碱基都伸向外侧，彼此之间不相干。 3月12日，沃森致函德尔布吕克，借助于草图作说明，论述了他们设想的新模型。他再三要求自己这位导师不要把此事向鲍林透露，等到他们对这些结果更有把握时再说。但是，德尔布吕克向来就是嘴巴锁不牢的人，他马上就将此信到处让人传阅了。鲍林一面读着这封信，一面在头脑里进行着紧张的思考。他马上就认识到，在卡文迪什设想出来的这一种结构，不但在化学上是非常合理的，而且在生物学上也是十分迷人的。“两个嘧啶各自与相应的嘌呤在结构上互为补充，对这一简洁的想法我颇感意外——当然，这是令人欣喜的意外，因为它在遗传机理的问题上让人豁然开朗起来了，”他这样说道。鲍林还从中看到，自从他1940年与德尔布吕克一道写的论文发表以来，在他一直在思考和著述的一些问题上，已经有人在仿效他使用互补性概念。 亚历山大·里奇在第一次听到有关沃森一克里克结构的那一天夜里，他突然醒来，起身下床走进了办公室。他利用原来堆在那里的分子模型的部件，动手为沃森一克里克的双螺旋制作一个粗糙的模型。他了解到的唯一结论是DNA碱基应当穿过分子的中心，不过知道这一点已经足够了。他很快就将碱基配成了对，看来这个模型的确很漂亮，于是，他摇了摇头，又回到床上睡觉了。 鲍林尽管还不甘心在这场竞赛中认输，但在思想上受到了很大的触动。在读到沃森的信以后几天，他致函一位同事说：“当然，你应当承认，我们的结构还只是一种设想，它可能是正确的，但我们要有真正的把握，也许还得有两到三年的时间……”。几天以后，他收到了沃森和克里克论文手稿的单行本。文中批评了鲍林的DNA模型，结尾处对多诺胡给予的帮助表示了感谢。鲍林将此文从头至尾读了一遍，然后写信给他的儿子说：“我想，为核酸提出了两种结构，是一件好事，我期待着有一天能作出定论，到底哪一种结构不正确。毫无疑问，金斯学院的资料会在这两种结构中否定掉一种。” 此时，他仍未能看到富兰克林和威尔金斯拍摄的Ｘ射线新照片，因此，他一直没有作出最后的判断。他不久就会有机会：他正打算在4月份去布鲁塞尔参加一次关于蛋白质的索尔维会议，顺便想在英国停下，看一看沃森一克里克模型，看一看威尔金斯和富兰克林实验室拍摄的照片。在他申领护照时，他的宿敌露丝·希普利又再次作出了拒发的提议。这一次她的根据是，她认为鲍林在就业资格审查委员会的证词表明，他拒绝接受参阅绝密级资料的资格审查。鲍林解释道，他在以前已经通过了绝密级资格的审查，再说，他也愿意再次受审查，但总得与他的工作有关系——在他再次当着她的面发誓否认自己是共产党员以后——他的护照总算得到了批准。 4月初，就在克里克和沃森将论文送出发表后的几天，鲍林来到了剑桥。当天在彼得处过了一夜，第二天就走进了克里克的办公室，第一次看到了他们冲压出来的金属板搭接而成的三维模型。在鲍林仔细地察看模型的过程中，克里克精神紧张地述说着双螺旋模型的特点。鲍林看来又察看了富兰克林为扩张形式分子拍摄的照片。沃森和克里克急切地等待着鲍林的表态。此时，“他表现出一副洒脱的样子，”沃森回忆道，“发表意见说，我们找到了答案。” 对于这两位年轻人来说，这是一个充满喜悦的时刻；但是对鲍林来讲，这是一次不小的挫折。鲍林感到非常惊讶的是，这个井不起眼的研究组，其中一人是资格尚嫩的博士后研究者，另一人是年龄偏大的研究生，竟然为这么重要的一个结构找到了如此漂亮的解决办法。如果他们是正确的话，那么他本人提出的模型将是一个十分荒唐的错误，不但将内外颠倒了，而且连链数都不对。不过，此时他已经认识到，这个卡文迪什研究小组得到的结果几乎可以肯定是正确的。 现在，只剩下一件事他可以做一做：向全世界表明，他是怎样潇洒地对待自己的失败的。 鲍林从克里克办公室出来，吃中饭时碰到了布拉格。在他们用餐过程中，布拉格怎么也掩饰不了内心万分喜悦的心情。经过这么多年矮人一等的经历，他的研究组终于打败了鲍林！后来，鲍林出席了克里克一家人在葡萄牙广场的自家寓所里举行的一次喜气洋洋的宴会。人们自始至终都可以看到鲍林这个人谈笑风生，举止优雅，他衷心地赞美DNA的新结构，显示出一派绅士的风度。他机智地承认自己的失败，同时气度非凡而又不失幽默地接受这一个事实。又过了一两天，布拉格和鲍林一起去参加了索尔维会议——这是一次难得的世界顶尖科学家聚会，由一位比利时企业家赞助——会上，布拉格首次公开宣布了双螺旋结构。鲍林则在自己的发言中热情洋溢地表示了赞同的意见。“尽管离科里教授和我发表我们为核酸设想的结构只有两个月时间，但是我认为，我们应当承认自己很可能弄错了，”他对大会的参加者这样说。“虽然对沃森一克里克结构还可以作一些精细的修改，但我感到，就本质上而言，这一结构很可能是正确的。” 然而，在情感深处，鲍林却心急如焚。在英国，他可以毫无保留地称赞沃森和克里克的工作，但他在私下里仍认为，也许能找到意外的机会，可以证明他本人的想法在经过若干修改后仍有正确的地方。在他4月中旬回国后不久，他关照里奇赶快拍摄DNA的Ｘ光新照片，他本人也重新开始对自己模型中各个原子的位置作更加精细的测定。 这是一件毫无希望的事。事实很快就表明，他这样做，实际上是在世界科学的舞台上给人留下了笑柄。在沃森一克里克的论文发表以后，他们立即受到了来自世界各地的称赞和喝彩，而鲍林的模型最终落到了被人抛弃和遗忘的命运。在此之前，鲍林也曾经出过错——特别是在人造抗生素和相对来说不那么重要的几个问题上，还有小分子结构——但是，在这样一个众所周知而又如此重要的课题上，他可从来就未闪失过。况且，作为世界上首席结构化学家，他竟被两个初出茅庐的新手打败了，这一切难道还不是奇耻大辱吗？ 到底在哪里出了毛病？ 每个人似乎都有自己的看法。彼得认为，问题在于鲍林严格地限于用化学方法研究DNA，一心迷恋于磷酸的包装，忽视了对其生物功能的思考。“在我父亲的眼里，核酸只不过是令人感兴趣的化学品，正如氯化纳是一种有趣的化合物一样，”彼得写道。不过，严格地说，这并非是事实。鲍林在加州理工学院受到过摩尔根的影响，因此从30年代起就开始对基因感兴趣。他曾在1937年谈到过“对染色体结构作一次化学的研究”，并且在40年代后期有关互补性的一次谈话中，就将基因的复制看作为一个处于中心地位的概念。对于基因是怎样复制自己的，他头脑里有一种非常牢固的看法：基因开始时是两种互补结构的复合体，每一种结构是创造另一种结构的基体，两者在一起就构成了这个复合体。他曾经迷恋过自己这一美妙的结构，甚至达到了不能自己的程度，并且估计以后一定会有生物学事实来证明其正确性。 切加夫则认定问题是显而易见的：鲍林“没有利用自己的成果”。威尔金斯认为鲍林“只是没有亲自动手试一试，他本人甚至不愿花上五分钟时间真正研究一下这一个问题”。舒梅克则从理论的角度进行了概括，认为鲍林没有在这个问题上安排足够的人力去搜集充分而过硬的数据。里奇补充说，加州理工学院的同事们在考察鲍林的模型时，还不够挑剔，因而也要承担一部分责任。“在一定程度上，”他说，“他周围的人也不够卖力。” 对于自己是怎样迷失方向的，鲍林有他自己的想法。开始时，他埋怨自己使用的Ｘ光照片。鲍林在访问卡文迪什后一星期左右，就致函德尔布吕克，说这些糟糕的衍射资料使他抓不住要领。“我们手头的Ｘ光照片是里奇博士拍摄的，本质上与若干年以前阿斯特贝里和贝尔拍得的照片并没有两样，实际上这是两种类型的分子重叠一起的结果。……科里和我曾想找到一种结构，它既能解释一种类型的主要特点之一，又能解释第二种类型的一个主要的特点。 后来，他又更加强调是因为把DNA的密度搞错了，这一错误导致了三链结构的设想。“我误入三链结构的陷阱，原因在于我不清楚这些化合物中水的含量到底是多少，”他这样说道。“这种化合物中三分之一以上的物质是水，核酸则不到三分之二，因此，我在计算过程中忽视了水的含量，从而得出了三链的结论。要是水含量计算得正确的话——我没有意识到水的作用这么大——那就会得到双链结构了。 鲍林还责备自己对DNA的成分缺乏有关的知识。“如果我们对嘌呤和嘧啶进行过一些研究的话，那么我就会具备必要的基础知识，从而就可保证研究工作不会偏离正确的方向。然而我们对嘌呤和嘧啶根本就没有作任何研究。 每一种说法都有一定的道理，但都只是谈论到问题的外表，并没有触及问题的本质。 鲍林之所以在DNA的研究中跌了跤，可以归之于两方面原因：浮躁和自负。他急于求成，因为DNA是当时最大的研究课题，要是他不去攻克，就会有别人——很可能是某个英国人——很快去抢占这一个高地。尽管他否认自己在DNA结构问题上在与英国的学者竞争，——“我并未感到自己在与沃森和克里克竞赛，”他说道。“倒是他们认为在与我竞争”——实际情况是，他确实在竞赛，对手不是沃森和克里克，而是威尔金斯和富兰克林，特别是还有他的老对手劳伦斯·布拉格爵士。鲍林之所以希望很快就公开自己的DNA结构，目的就是要打败布拉格的课题组，打败威尔金斯的课题组。但是，他还没有把研究的准备工作做好就想碰碰自己的运气了。 更为重要的是，他急急匆匆地行事，原因还在于，他认为自己有办法补上留下的漏洞。他在阿尔法螺旋上取得了成功，因而变得很自信，认为自己完全能跳跃着前进。他在30年代后期作出的基本假设全是正确的；在15年中所作的深入研究全都证明了这一点。他关于氢键、平面肽键和非整数循环等所作的探索都得到了正确的结果。只要他坚持在他所熟悉的化学领域里驰骋，他就无往而不胜。 阿尔法螺旋给他套上了成功的光环，同时也让他染上了自负的恶习。在解决了阿尔法螺旋问题后，他以为自己不再需要做别人需要做的那些研究的准备工作了。很清楚，他是世界上解决巨分子结构——甚至包括其他各种分子结构——的最佳人选。他知道，自己曾用两年的时间将阿尔法螺旋的基本结构正确地装配起来，然后才发表有关的结果。在这长长的两年中，布拉格随时都可能找到其答案，将自己甩在后面。那时，鲍林曾一再迟疑不决，因为他吃不准5.1埃这个Ｘ光反射的数据，经过试验才观察到，这个数据根本与结果无关。他一定要相信自己的直觉，相信自己对结构正确性所具的敏感。他知道自己的三链DNA结构实在太紧密，知道带有负电荷的磷酸存在着互相排斥的问题，但是他相信这些问题以后必定会得到解决，正如在阿尔法螺旋问题上，那个迟迟无法说明的反射现象最终还是作为盘绕螺圈的特性得到了解决。在他的模型中心部位装磷酸，看上去是那么漂亮，那么巧妙，不可能是错误的。 他渴望着抢头功，他投下了赌注，结果却输掉了。 尽管他不久又像平常一样，兴高采烈地回到了实验室，但是，在他后半辈子生涯中，他当然会感到很后悔。在几个月时间里，他还在这个问题上与里奇开玩笑，问起他关于DNA的一种特殊形式课题有什么进展，最后会加上一句：“亚历山大，在这个课题上，你一定要加油，因为我希望大多数重要的发现都是在帕萨迪纳作出的。” 文献中，在阐述DNA发现的历史时，学者之间的明争暗斗无形中带上了种种传奇的色彩。沃森和克里克将位于舞台的中央，而鲍林只能充当幕后人物中一个较小的角色。这是一个远方传奇大力士被两个无名小卒砍倒的故事。1953年以后的一年里，任何人碰到鲍林，不管是科学家还是作家，都要问他是在什么地方失误的。 爱娃·海伦终于对此感到厌倦了。她听到这类疑问和解释后，总会用一个简单的问题来打断丈夫的话：“要是这个问题是那么重要的话，”她质问丈夫道，“你为什么在以前不更加卖力一点呢？”