Chapter 17 14 UK tour

Observation blind spot In the summer of 1947, Pauling and Eva embarked on a journey, a two-month visit to Britain and Scandinavia.Their visit to Europe this time is both a lecture and a vacation.They rejoiced at the chance to escape the deteriorating political climate at home.This time, the two still left all the children at home for Aletta to take care of.The couple went to New York first, and Pauling attended the conference on the basic theory of quantum mechanics held there.Then, the two flew to the UK on a new large long-distance passenger plane across the Atlantic.Although remnants of wartime bombing can still be seen everywhere in Britain, and supplies are also in short supply, the Paulings' stay in London was very pleasant.There, the Royal Society absorbed Pauling as an honorary member, and Cambridge University also awarded him an honorary doctorate. Throughout the afternoon of June 12, Cambridge University held a degree conferring ceremony in the school's resplendent council hall.Dressed in full doctoral gown, Pauling marched through the packed hall alongside the former British governor-general in India, the Portuguese ambassador and eight other dignitaries.After they were seated, they began to listen to the latin acknowledgment read by the university spokesman, which mentioned that Pauling had successfully "solved the mystery of ... the original structure."This very grand degree conferring ceremony became a climax of Pauling's visit to Britain.

After visiting London, the Paulings traveled to Scandinavia.They attended the scientific congress that was being held there, and spent a long vacation happily by the sea. In August, they flew back to California refreshed with satisfaction and joy.They were eager to return home to take care of their personal affairs so that they could go to England together again in the winter.Pauling was invited to be a six-month Eastman Lecturer at Oxford University. The children cheered to see their parents come home, and they were especially happy that they would accompany their parents to England in the winter, when there was so little family time together.Peter has been doing poorly in school; Linda, who is smart, cute and quiet, is 15 years old. She tries to please her father, but she is always afraid that he will not take her to England; Clarelin is only a 10-year-old boy. Dissatisfied with being away from home often.

Little Linus is doing well.That autumn he surprised his parents by announcing his sudden engagement to Anita Orsay.Orsay is the great (outside) granddaughter of McCormick ①Rockefeller ② and the heir to the largest private fortune in the country.Their love has a fairy-tale tinge—one is the calm son of a respected scientist, the other is the beautiful daughter of the wealthiest man in the United States, so the news of their engagement was widely reported in the media. In September, the couple married austerely on the lawn of Pauling's Medel residence.For Pauling, this was another great occasion; he felt that things in the world should be arranged in this way.He toiled all his life to realize his American dream; and now, on the green lawn of this hillside mansion, under the golden Southern California sun, a group of wealthy and prominent dignitaries toasted to each other, which undoubtedly announced to the world :He succeeded!

① McCormick (Cyrus McCormick, 1809-1884), an American industrialist and inventor, invented the harvester in 1831, became rich by building a factory to produce harvesters, and later formed the world's largest international harvester company (1902). ② Rockefeller (John D. Rockefeller, 1839-1937), the founder of the American Rockefeller consortium, founded the Ohio Mobil Oil Company (1870), reorganized it into the first trust in the United States (1881), and later served as the chairman of the New Jersey Mobil Oil Company (1899 —1911), donated to establish the University of Chicago (1892) and some charitable institutions.

In late December, Pauling, Eva and their three children took the train to New York, and were scheduled to leave the United States on the Queen Mary the day after Christmas.They stayed at the Manhattan Hotel downtown.Families exchange Christmas presents in the room.Looking out of the window, they were pleasantly surprised to find that there was heavy snow falling in the sky. This was the first time the Pauling family spent a white Christmas.The whole family happily ran outside to play in the snow, and even Pauling and Eva squeezed snowballs and threw them at street signs. However, I was dumbfounded when I saw it the next morning: a good thing is too much!A blizzard overnight buried the whole city in snow, there were no moving vehicles on the street, and the ship would sail within a few hours, Pauling was as anxious as an ant on a hot pot.Finally, they found a taxi, and the driver expressed his willingness to try his best to send them to the pier—of course, the fare was very high, and finally arrived at the pier on time.

The kids were so happy when they got on the boat, they had never been so happy.The captain postponed the departure time to wait for the passengers who were delayed by the heavy snow.During this time, the three children ran from bow to stern and couldn't get enough of them.Even their modest cabins—Pawling bought third-class tickets to save money—seemed full of novelty and fun.Finally, the whistle sounded for a long time, and the Queen Mary slowly left the pier in the heavy snow. After the ship rushed out of the wind and snow, the whole voyage was relatively smooth, and the children were only slightly seasick.One day during the journey, Pauling was walking on the top deck when he came across a chemist named Chargaff.This person is an expert in nucleic acid research. He introduced Pauling to his recent research results on molecular secondary structures (a structure similar to purines and pyrimidines), and tried to arouse Pauling's interest.But Pauling, who was on vacation and found this fellow a bit boastful and boastful, was quite disgusted, interrupted him, and hurried back to the cabin.Later, Pauling recalled: "I didn't listen to his speech carefully." Pauling's always active thinking did not respond to new information this time and let it go, which is unique in his life , and he will regret it later.

After Pauling arrived in the UK with his family, it took him a week to settle the family down.They live in a flat in London and enroll their children in local private schools.Then Pauling began what he later called "one of the happiest years of my life."At Oxford, he was a typical Yankee, lean, lanky, energetic, witty and good-humoured.His black robes and long gray hair flowed behind him as he strode across the schoolyard of ancient arches and battlements.Students and professors flocked to hear him lecture. “He was a sensation. The lecture hall was so full of students that the latecomers had to stand,” one student who was lucky enough to squeeze into the lecture hall later recalled. “I never heard such a wonderful lecture. He delivered lectures with ease and wit. His cheerful smile, calculations with the aid of a slide rule, and spontaneous sparks of thought left an unforgettable impression.”

In the evening, the Paulings were either invited to dinners or parties (they were overwhelmed with invitations), or to go to shows, lectures, or concerts.Pauling constantly met with scientists, industrialists, politicians, and municipal dignitaries, and whenever it came to political or scientific issues, Pauling's conversations always attracted them strongly.All sorts of honors followed, he was elected a foreign fellow of the Royal Society, and was conferred simultaneous doctorates by Oxford, London and Cambridge—he was, he was told, the only one so far the recipient of this honor. The British Chemical Society invited him to give lectures throughout the United Kingdom, including three dedicated lecture series at the Universities of London and Cambridge.His report mainly focused on the theory of molecular complementarity.With the help of a standard molecular ball-and-stick model, his report is more lively.He often said to his audience: "Look here, if the atom is really as big as this ball with a diameter of 2 to 3 inches, then according to this ratio, a person observing this atom will be 250,000 miles high, that is, his body length is equal to The distance from the Earth to the Moon."

The man with the moon on his head later became a metaphor often used in Pauling's reports. He used this metaphor on various occasions to illustrate the challenges faced by scientists who are interested in overcoming the structural problems of macromolecules.He asked the audience to imagine themselves as a giant 250,000 miles long, so that the earth you see is the size of a billiard ball.You can see buildings like Central Park or Rockefeller Center that are 1,000 feet wide on Earth; and if you use a new type of electron microscope, you can see the Empire State Building—but not the inside of it, of course. structures, and tiny black dots—that's the cars on the street.You can use a translucent film and an ultracentrifuge to measure the size of the car.But down there is a gap in measurement capabilities.The finer ones can be measured using X-ray crystallography or electron diffraction, a technique so incredibly precise that it can determine the shape of pins, rivets and gears on an automobile, but not the smaller parts. They are bigger things.

As a result, there is a gap in the observation ability, a blind area of ​​observation between the resolution ability of the electron microscope and the X-ray diffraction resolution technology.For the 250,000-mile man, the blind spot meant he couldn't determine the shape of things between a foot and 10 feet in size, including being the builders of Central Park and the Empire State Building, as well as objects like cars and rivets shape of the maker.Go back to the normal scale and ask the same question, and you'll find that this "dark region of the unknown"—as Pauling calls it—is roughly within the volume of proteins and other large molecules.It is this unexplored area that is now calling for focused research.

In February 1948, Pauling was invited to give a Friday evening lecture at the Royal Academy of Sciences. This kind of lecture is very formal and held once a month. It was originally founded by Faraday in 1825. The participants were all from the British scientific and technological circles and society. Celebrities from all walks of life.In the early days, people regarded science as art, and scientific reports were appreciated like handicrafts; at that time, this lecture was created to provide rich people in London with an opportunity to appreciate the latest achievements in scientific research.But then it gradually evolved into an important scientific symposium, and only those who had achieved significant results were invited to give reports-for example, when Thomson gave a lecture here and announced the discovery of the electron.A frequent lecturer recalled: “The audience were connoisseurs with a high artistic appreciation for good reports. Both the speaker and the audience wore formal evening gowns, and the reporting process was strictly in accordance with traditional etiquette, full of a an atmosphere of commensurate importance." ①Michacl Faraday (Michacl Faraday, 1791—1867), a British physicist and chemist, discovered the phenomenon of electromagnetic induction (1831), the law of electric energy (1834) and the relationship between magnetism and light (1845), and studied the diffusion of gases and the liquefaction of alloys properties of steel, etc. ② Thomson (Sir Joseph John Thomson, 1856-1940), a British physicist, was a professor at Cambridge University (1884-1918), dean of Trinity College (1918-1940), discovered electrons (1897) and isotopes (1912) ), won the 1906 Nobel Prize in Physics for his research on the conduction of gases. For his Friday night presentation, Pauling carefully prepared the exact hour-long speech required.The presentation was preceded by a formal dinner.After the dinner, Pauling was taken into the office where Faraday, the father of electronic chemistry, once stayed.The offices are quaintly furnished and well kept.Pauling was left there alone, clearing his mind one last time for his presentation. An hour later, the calm Pauling walked into the small ornately decorated auditorium.The audience sitting in the audience are specially invited, men all wear black ties, women all wear fur coats and jewelry.Reflecting on the essentials of oratory he had learned as a student at Oregon Agricultural College, Pauling took a deep breath and began the following speech: When I look at a living organism - any one of you or myself - I see many phenomena.These phenomena raise a series of questions that need to be answered... What is skin?What are nails?How do nails grow?How did I have a sense of touch—what is the neural structure like?How does it work?How do I see things?How do I smell and why do benzene and isooctane not smell the same?Why is sugar sweet and vinegar sour?How does the hemoglobin in my blood carry oxygen from the lungs to the tissues?How do the enzymes in my body break down the food I eat, burn it to maintain my body temperature, and create new tissue in my body?Why does exposure to a sick person make him catch colds and pneumonia, while taking a certain antiserum or sulfonamides can make him recover?Why does penicillin have such a miraculous healing effect?Why do I have measles, whooping cough.Polio, smallpox are immune, and some people are not?Last but not least, why do my children grow up to display the characteristics of me and their mother - how are these characteristics transmitted to them? All these questions have no ready-made answers from books.Although Chaucer ① said so ① Chaucer (Geoffrey Chaucer, 1340-1400), an English poet, wrote in the London dialect, making it a British literary language. The masterpiece "Canterbury Tales" reflects the life of all social classes in the 14th century in England , embodies the thought of humanism. However, "in this ancient soil / year after year grows new corn / and in this old scriptures / all new sciences of human learning," but Bacon corrected him not long after Francis Bacon (Francis Bacon, 1561-1626), a British philosopher, a master of English language, and the founder of British materialism and experimental science, opposed scholastic philosophy and proposed that knowledge is power. His main works include "On the Value and Development of Science". The saying: "Books should obey science, not the other way around." In order to understand these important biological phenomena, we must understand atoms and the molecules formed by the bonding forces of atoms. Combining scientific issues, everyday examples, and quotations from giants of English literature and science, Pauling captivates his audience's attention from the start.He then gave an overview of his theory of complementarity as a basis for explaining biomolecular interactions.Usually, the speaker of the Friday evening lecture always stands stiffly behind the podium and reads from the script, while Pauling speaks out of the script, holding chalk in his hand, walking back and forth on the rostrum, and at the same time sketching the shape of the antibody and the shape of the antibody on the blackboard. Schematic diagram of enzyme action.He asked the audience to imagine that they were giants whose height was equal to the distance from the earth to the moon, and guided them to understand that the problem of protein structure is the central problem of biology.His report was an impeccable, one-stop performance of excellence, with desired effect.At a party after Pauling's speech, Sir Helbro, the president of Imperial College, made this evaluation: "When we listen to Linus' report, we feel that we are listening to a genius narrating his own thinking process. .” Cavendish Laboratory Among the people who attended that evening was a luminous man named Lawrence Bragg, also a physicist who kept his eye on the structure of proteins.Since Pauling proposed a set of rules for determining the complex silicate structure, Pauling has surpassed Shilager.Over the ensuing 20 years, their careers followed two parallel upward trajectories.Bragg emerges stronger than ever from the psychological setbacks of the early 30s.More confident, the Manchester X-ray Crystallography Laboratory under his leadership has become one of the most theoretically creative research institutions in the world. In 1938, his efforts finally paid off, and he was called to succeed Rutherford as the director of the Cavendish Laboratory in Cambridge, the largest physics research center in the UK.He was knighted three years later. By 1948, he had built the Cavendish Laboratory into the world's most advanced X-ray crystallography research center.At this point, however, his and Pauling's interests parted ways.Pauling was interested in the results of X-ray diffraction; Bragg was interested in the process of diffraction. He devoted himself to improving equipment and developing mathematical techniques for explaining X-ray diffraction patterns.The reason why the Cavendish Laboratory is famous all over the world is that Prague has a complete range of equipment and is powerful; it is because of the smart and capable young researchers he has absorbed; it is also because of the fruitful achievements made by Prague himself in his long-term unremitting research on diffraction theory. results.As for the research on the molecular structure, Prague mainly asked the staff below to do it.Their research objects were mainly limited to minerals.alloys and small organic molecules.But when Bragg first arrived at the lab, a group led by the Austrian-born scientist Perutz was also working on the structure of hemoglobin, an effort Bragg called a "courageous attempt."Bragg was initially not very interested in the study of protein structure—he had always lost track of biology, and thought that protein molecules must be too large and complex to be studied by X-ray diffraction—but Perutz was a A tireless and confident researcher who had done enough research to interest Bragg to make him realize that the study of proteins was a challenge to x-rays, a class of subjects that surpassed the study of minerals.By the time Pauling came to England, Prague had secured enough funding for Perutz and his young colleague Kendrew and two other assistants, who had also achieved a number of important results, revealing many kinds of The approximate structure of the hemoglobin molecule.And the research group in the UK is not alone in making important advances in protein research.Elsewhere, Hodgkin's insulin research is entering its second decade; Bernal and his colleagues have begun work on cleaving ribonucleases. ①Max Ferdlnand Perutz (Max Ferdlnand Perutz, 1914), an Austrian-born British biochemist, won the 1962 Nobel Prize in Chemistry with JCKendreu for the X-ray diffraction analysis of the structure of globular proteins, especially hemoglobin. prize. ② Dorathy Crowfoot Hodgkin (Dorathy Crowfoot Hodgkin, 1910—), a British female chemist, cooperated with colleagues to obtain the first X-ray diffraction photo of vitamin B12 (1948), determined the atomic arrangement of vitamin B12, and won the 1964 Nobel Prize in Chemistry . The more Pauling learned about the Briton's work, the more he worried that he might be the loser in the race to be the first in the world to completely determine the molecular structure of a protein.His method of solving the problem of protein structure is from the bottom up, that is, first carefully determine the structure of individual amino acids and small peptide molecules, and then assemble the macromolecular structure on this basis; in contrast, the British method is from the top Next, analyze the X-ray diffraction pattern of the intact protein.Pauling had thought that protein molecules were too large and their X-ray diffraction patterns too complex for a top-down approach to work for the foreseeable future.But after talking with Bernal and Hodgkin, Pauling realized that the British were getting close to solving the structural problems of certain protein molecules, which made him feel a lot of pressure. Under such circumstances, he once again considered theoretically solving the structure of the protein's mother body, the keratin chain, which he had tried in 1937.He tried unsuccessfully to construct a protein chain that would match Astberg's X-ray data.So he suspected that his ideas about amino acid structures or bonds were wrong.But years of research, including the specific research Corey had done on amino acids, told him he wasn't wrong.The molecular scale roughly matched his hypothesis.He also predicted that the bonds of peptide molecules have the characteristics of double bonds, and the atoms on both sides are fixed on a plane. This speculation was also confirmed by Corey's research results on diketopiperazines.He was actually very close to success at the time, and it was incredible that he didn't stick to it. In the spring of 1948, he revisited the problem, but this time with new guidelines.In the 1930s, chemists had proposed that long-chain starch molecules had a structure like a spiral ladder. Pauling's early partner Huggins (with whom Pauling had done some early research work together, finally came up with the peptide The planarity conclusion of bonds) has theoretically demonstrated that this helical structure is also the main structural form of protein molecules.According to the Huggins model, the shape of the amino acid chain is not the flat, kinked ribbon assumed by the Astberry model, but a spiral ladder, like a mattress spring; Huggins also assumes that the loops and loops of the chain They are fixed by hydrogen bonds, thus maintaining the stability of the structure. This is a very instructive hypothesis, and has already aroused heated discussions among British crystallographers.These assumptions help explain some phenomena.According to Astberg's flat ribbon model, the chemical properties of the protein should reflect the two-sided nature of the ribbon, however, the protein chains actually appear to be isotropic, which coincides with the overall shape of the cylinder formed by the helices match.In addition, theoretical extrapolation results are also in favor of the spiral hypothesis.As Crick,1 who was a graduate student in Perutz and Kendrew's lab at the time, put it, "It is well known that if a chain is folded and connected in exactly the same way by identical rings, and The relationship between each ring and the adjacent ring is also exactly the same, so such a chain forms a helical structure." Whether it is called a helical structure or a helix, anyway, Huggins' hypothesis has a great impact on Cavendish researchers. had an important impact.Soon it seemed that every protein researcher in the UK was looking for helical structures.Hodgkin, for example (with whom Pauling had several long talks when she visited Oxford), paid close attention to finding evidence of a helical structure in her work on the insulin molecule. ①Crick (Franis Crick, 1916—) British biophysicist and geneticist, because of his participation in making the molecular structure model of deoxyribonucleic acid (DNA), laid the foundation for the division of genetics, and Watson ( J.Watson) and Wilkins (M.Wilkins) shared the 1962 Nobel Prize in Medicine. More than a week after the Royal Academy report, Pauling fell ill.Due to the wet weather in England, he suffered from severe osteosinusitis and had to stay in bed.He remembers: "The first day I read detective novels to keep myself from having bad luck, and the second day was the same. But the third day I got bored and I thought, 'Why can't I think about the structure of proteins? In this way, he decided to make another attempt to study the structure of keratin chains. But this time he used the idea of ​​a helical model. He prepared a pencil, ruler and some paper, and began to draw a sketch of the amino acid chain. According to memory, He sketched the lengths and angles of atomic bonds. He used a three-step working method: first, draw the chains according to the known dimensions of amino acids; second, arrange the elements in space in such a way that The hydrogen bonds are easy to form and keep the titanium bonds in the same plane; the third step is to check whether the resulting model can explain the X-ray diffraction data. He drew the basic carbon-carbon-nitrogen skeleton of each amino acid molecule, and then He represented the peptide bonds with thick lines, and connected them, and these peptide bonds remained straight on the page. He also drew the side bonds that distinguish different types of amino acid molecules as line segments pointing from the center of the helix to the outside. Through this representation, these side bonds will not interfere with the repeat structure present at the central site, Then he folds the paper.Folding keeps the peptide bonds flat on the page and only knuckles at the single carbon atoms in the amino acid backbone where the peptide bonds are attached, which is where he thinks the rotation might occur.He managed to fold the angles roughly equal to the tetrahedral angles, the size of the folds that is most natural for carbon bonds.He folded the paper in various ways, trying to arrange the elements in just the right way to form as many hydrogen bonds as possible.It didn't take long before he came up with a beautifully shaped spiral structure.This made him overjoyed.This structure has planar peptide bonds, roughly correct bond angles and lengths, and an appropriate number of hydrogen bonds at the corners. "I just forgot I had a cold and I was so excited," he said. This is a typical example, which can well illustrate the characteristics of Pauling's stochastic method: a few limited chemical rules that play a key role are used to construct a reasonable structural model.Pauling's excitement waned, however, when he realized that the X-ray diffraction patterns derived from his model likely did not match those produced by Astberry and others.Natural keratin molecules show a strong reflection of 5.1 angstroms, a length considered to be the distance between two repeating units in the axial direction of the chain—in a helical structure, between two adjacent coils of the chain. distance between.It would take several months of careful modeling to test this possible outcome in a spiral pattern, but already from his rough sketches it seems clear that his spiral pattern will produce different periodic spacings.Calculating by applying his own rules for peptide bonds and hydrogen bonds, Pauling discovered: "I cannot stretch or compress my structure." Pauling went back to bed.He didn't show off his scribbled sketches, or even write to Corey.He just stored the spiral idea for further exploration when he returned to Caltech.As he puts it, all he has is "just a piece of paper" for the time being. the tortoise and the hare Pauling's osteosinusitis lasted for several weeks. When he took his family to Paris for an academic visit, he still hadn't healed. After Pauling settled the residence, he persuaded the doctors of the American embassy to give him some penicillin. After taking it, the inflammation Sure enough, it disappeared quickly.Eva and the kids took time out to explore the park, visit museums and cathedrals, and shop for groceries, while Pauling was busy attending various social events in the French scientific community. At a scientific symposium Pauling attended, the conference organizers set aside a full day to discuss and compare the advantages and disadvantages of Pauling's molecular valence bond theory and the University of Chicago Mulliken's molecular orbital theory.This discussion became a hot spot for the participants. ①Mulliken (Robert Mulliken, 1896-1986), an American chemist and physicist, proposed a quantum mechanical theory of the orbital behavior of electrons when different atoms combine to form molecules, and won the 1966 Nobel Prize in Chemistry. In the ever-growing community of quantum chemistry, the debate between the two theories is seen as somewhat akin to the challenge of Pope Martin Luther.Starting from the same "bible", that is, the accepted principles of quantum mechanics, two scientists have made very different interpretations of its chemical meaning for nearly 20 years. ①Martin Luther (Martin Luther, 1483-1546), a German, was the initiator of the European Reformation Movement in the 16th century and the founder of Protestant Lutheranism. He published the Ninety-Five Theses (1517) and criticized the Holy See Selling the Atonement Book, denying the authority of the Pope, and translating the Bible into German. The Pauling theory derived from the electron exchange ideas of German chemists Heitler and London believes that molecules are superimposed bodies of different atoms.Atoms are connected to each other by bonds, which are formed by a number of electrons positioned between two atomic nuclei.The number of bonds is equal to the valence of the element, that is, the bond capacity of the element, so the Pauling school is called the valence bond school or the VB school.Theoretically, the total quantum mechanical state can be calculated by superimposing the wave functions of each bond.Of course, the calculation results need to be properly corrected according to the effect of each key on the adjacent key. During the nearly 20 years when Pauling vigorously promoted the VB theory, Mulliken patiently studied his own molecular orbital (MO) theory. He firmly believed that molecules were not as the VB theory advocates imagined.In Mulliken's view, a molecule is not an aggregate of different atoms connected by different bonds, but an indivisible whole whose unique behavior can only be explained from the molecule itself.He has studied the phenomenon of molecular absorption and emission spectra, and his research experience in this area has convinced him that the bonding electrons should not be regarded as fixed in a certain position, but should be regarded as distributed on the entire surface, so that it can be better explain the behavior of molecules.Although this theory is not intuitive to most chemists, after 20 years of research, Mulliken is convinced that the theory is correct.Mulliken believed that molecules should be what they actually were, not what nineteenth-century chemists imagined they should be.He summed up his point of view by borrowing the words of the American female writer Stein: "The definition of a molecule is: a molecule is a molecule." ① Stein (Gertrude Stein, 1874-1946), an American female writer, moved to Paris (1903), advocated avant-garde art, and used repetition, fragmentation, and simplification in writing. Her works include the novels "The Lives of Three Women", "The Autobiography of Abes B. Toklas", etc. In the debate between the valence bond theory and the molecular orbital theory, most chemists agree and accept the valence bond theory. One of the main reasons for this result is the important role played by Pauling's intelligence and personality.Pauling knew how to explain his valence bond theory so that chemists were happy to accept it.Atoms are connected to other atoms one at a time by different bonds, which can be represented on paper by dotted lines connecting the symbols of the elements, which is consistent with the way chemists think about chemical bonds.Equally important, Pauling was good at finding shortcuts to simplify math.Although theoretically speaking, the quantum mechanical description of molecules can be obtained by superimposing different wave functions, but in the absence of electronic computers at that time, except for some of the simplest molecules, the mathematical calculation of general molecules is very difficult , is actually not feasible at all.Pauling proposed some semi-empirical workarounds to circumvent this difficulty, such as the calculation of resonance energy and electron negativity level, these workarounds are in line with the spirit of quantum mechanics, but their basis depends on Yu Pauling's intuitive imagination.Chemists do not need to know how to superpose wave functions to apply Pauling's theory.This simplistic approach made Pauling's theory more and more popular in the 1930s and early 1940s.This is especially the case after Pauling's monograph "The Essence of Chemical Bonds" was officially published.Applying Pauling's method means that chemists have dabbled in the latest physical theory, but they don't need to study physics at all; Pauling's own ability, his intellect and personality, played a decisive and arguably the most important role in the promotion of the valence bond theory.He was an outstanding teacher and a charismatic speaker.He can attract people to believe in his theories.Influenced by himself or his writings, researchers have turned to his methods.By the 1940s, valence bond theory seemed to have conquered the chemistry community. Mulliken simply couldn't compete with Pauling.Not only did his basic concepts turn off many chemists because they were too esoteric, but also because he packaged them in such abstruse ways that they were difficult to read (he used Greek letters for molecular orbitals, subscripts and subscripts), but also because he was a poor communicator of information—too precise, too mathematical, too much rigor to render his theories quite dull.At the University of Chicago, he lectured so poorly that he bored the chemistry students.His profound insight is shrouded in the fog of difficult and gloomy theory, which makes people puzzled.Most of his papers are published in physics-related journals and are difficult to read. For many years, Mulliken could only watch so many honors and awards fall on Pauling's head.He saw that Pauling's series of papers on "The Essence of Chemical Bonds" published in the 1930s was praised as a revolutionary achievement, while his own series of 14 papers published in the same period "Electronic Structure and Valence of Polyatomic Molecules" But no one cares.He saw that the classroom was overcrowded when Pauling lectured, but the students shunned him.He saw that invitations and honors were given to Pauling one after another, but he himself could only stay at the University of Chicago as a hardworking teacher. What particularly annoyed Mulliken was Pauling's contempt for his theory.Pauling does not think his theory is wrong - Slater and Pauling as early as 1931 affirmed that the valence bond theory and the molecular orbital theory are good approximations to the wave equation.出同样的结论；而且鲍林本人在自己早期的几篇论文里还采用了分子轨道理论的有关概念——但是鲍林却坚持主张，他的价键理论对化学家更实用且更适合于教学。 “有一种理论已经足够了，”鲍林写道，“分子轨道只能把学生搞糊涂。”在他1935年出版的《量子力学导论》一书中，他用了相当大的篇幅论述价键理论，而只写了一小段文字把分子轨道理论一带而过。在《化学键的本质》一书中，他对马利肯的理论更只是顺便提了一句。 而马利肯却发现，风行一时的鲍林价键理论正在起着破坏作用。“鲍林是个演员，”他说，“他千方百计把每样事情都讲得通俗简单，这使他的理论在化学家中倍受欢迎；殊不知这样做的结果是使人们放弃了对事物的深入理解……他教给化学家非常粗略的概念并使他们自我满足，从而阻碍他们去做出更好的结果。” 在整个30年代，鲍林利用自己出色的演技将价键理论推上了唯我独尊的地位。但是到了40年代后期，越来越多的化学家开始学习马利肯的理论。主要由于鲍林的工作，这时量子化学已经走出了初期的普及阶段，在名牌大学学习的化学系高年级学生希望学习量子力学基础和更多的数学知识，以便在未来的化学研究中取得更好的成果。新一代化学家学到的知识越多，他们就越不需要鲍林的简化方法。他们渴望掌握这一领域中更加定量化的、不依赖于直观的理论。他们在马利肯的分子轨道理论中找到了所需的东西。 有些事情真像风水轮回，成败难料。举例说，在30年代，对氢分子用分子轨道方法进行分析时，比用价键方法可得出更精确的键长，却只能得出较差的离解常数。但现在人们逐渐看清，经过改进的分子轨道方法是研究复杂分子的更加有效的工具。人们开始公开批评鲍林的价键理论的某些概念，比如电子负电能级的概念。有些批评者说，这一概念虽然在很多场合是一种实用的工具，但是它缺乏坚实的理论基础，用来处理矿物元素时更不可靠。他们还批评鲍林用共振体来解释分子性质的方法。在实践中，这种方法依赖于选取若干个恰当的初始结构——即所谓的正则结构——在它们之间形成共振，然后再恰当地权衡每个共振体的贡献得出最后的结果。一般来说，分子越大，包含的原子越多，那么解释分子性质所需要的正则结构的数量就越多。鲍林具有超常的化学直觉能力，常常能得到恰当的共振体，但其他化学家就得不出，鲍林的一个学生韦兰特（他曾成功地应用价键理论进行有机化学的研究）走得更远，他引入一种所谓的“受激态”结构——纯粹想象出来的在自然界不可能现实存在的结构——作为共振体的构件，使事情更加复杂化了。一些化学家认为，这种做法无异于鼓励人们胡思乱想，把各种怪东西都塞到正则混合体中去，价键理论的任意性太大了。越来越多的化学家产生了这样的感觉：鲍林和他的追随者为了解释某种分子的性质，可随时从他们的帽子里变出所需的共振混合体。 到1947年，甚至韦兰特也承认，尽管共振概念从总体上看对解释化学现象很有用，但确定正则结构的数值时，“带有很大的随意性，很不可靠……然而我并不认为这种方法是完全没有价值的。当严格的处理方式行不通而不得不采取近似方法时，那么你只能引进某种程度的随意性，这是为了取得进展唯一可行的方法，只要头脑清醒，不把所取得的结果看得太认真，你就不会有大的麻烦，并有可能获得某些研究成果。” 但是，到了战后时期，很多化学家急于把量子化学变成一门严格的定量化科学。对他们来说，价键方法已不再是一种好方法。正如马利肯所说，“当涉及到复杂分子时，价键方法要求有大量的共振结构，而对这些结构进行计算几乎是不可能的事。”在30年代，马利肯在英国找到了一小批人数虽少但影响颇大的志同道合的量子化学家。在莱纳德一琼斯（他是英国理论化学学会的首任主席）和朗盖一希金斯的领导下，英国的分子轨道理论研究者积极发展马利肯的理论并推广他的方法的应用范围。比如说，就在鲍林和马利肯在巴黎进行辩论之前不久，莱纳德一琼斯提出了一种简易方法，利用分子轨道理论解释键的方向性，从而克服了这种理论的一个重大缺陷。 到40年代后期，通过鲍林、马利肯和他们的追随者对量子化学的艰苦深入的研究，有两点变得越来越清晰：分子轨道理论和价键理论的核心内容在本质上是一致的；而分子轨道理论学派为分子的定量化研究提出了更简单、更有用的工具。潮流从价键理论转向了分子轨道理论。 在法国举行的这次辩论会上，马利肯被允许的发言时间跟鲍林得到的一样长，这个事实本身说明了他的分子轨道理论已经有了巨大的影响。一整大的报告虽然再次证实鲍林是一个更有吸引力的演讲者，但辩论的结果却清楚表明，在过去的十年里，除了对金属的价键研究取得一些新成果外，鲍林在价键理论方面并没有做多少重要的工作。他的注意力转向了其他方面。然而马利肯却坚持在分子轨道理论领域里耐心耕耘，不断完善有关方法，他的方法已经更加适应新一代化学家的需要。一天的辩论结束后，并没有什么立时显现的后果，也没有大批人员的阵营转移；但它证实了一种发展趋势，即在未来的十年里，量子化学家将更欢迎分子轨道理论。乌龟追上了兔子。 讨论会后，马利肯和他的妻子来到鲍林在巴黎下榻的公寓参加晚会。当鲍林在众多化学家和物理学家中间周旋应酬时，马利肯夫妇静静地坐在一边。晚会气氛欢快，说笑声此起彼伏，人们时不时借用化学键开善意的玩笑。此外还有马利肯至今记得的“无数瓶的香滨”。鲍林女儿琳达即兴表演了一段独舞。晚会一直延续到深夜。然而，马利肯却悄悄地先行退席，在睡觉之前，他还要抓紧时间做一点研究工作。 镰状细胞 鲍林5月份回到伦敦后，到剑桥作了三次报告，这使他有机会对布拉格的卡文迪什实验室作出第一手的评估。佩鲁茨十分乐意充当向导。他非常钦佩鲍林，认为鲍林是世界科学界的巨人。佩鲁茨记得，当自己还是一个穷学生时，曾向女友借钱买了一本用过的旧书《化学键的本质》。他说，这本书“把我早先读过的教科书中的化学知识从平面转换成了三维世界”。鲍林对佩鲁茨关于血红蛋白的研究成果印象深刻。他的研究表明，血红蛋白分子总体上呈椭圆形。更重要的是，它看起来像是一堆堆蛋白质圆柱体，每个柱体的直径为10埃到11埃，沿着分子长轴的方向排列。鲍林注意到这个结果也许与他几星期前在病床上用纸折出的螺旋结构的尺度相符合。 但是他没有把这个想法说出来。“我并没有（向佩鲁茨）提起这件事，”鲍林说，“我总觉得还有点问题——很可能某个可笑的错误逃过了我的注意。”佩鲁茨的血红蛋白Ｘ射线衍射图显示了5.1埃的反射，而这不可能存在于鲍林的螺旋模型中。用未经证实的猜测把水搅混是毫无意思的，也没有必要把新的设想公开出来，让卡文迪什研究小组更快地深入到蛋白质结构研究的最后细节中去。 事实上，鲍林为在卡文迪什实验室的所见所闻而暗自焦急。布拉格——他很体面地接待了鲍林但仍然拒绝谈专业——把他的实验室建设成了一个晶体研究的窗口，实验室装备了各种最新的设备，使用这些设备的是那些最有才干的研究者。与此相对照，鲍林在加州理工学院的装备就显得陈旧落后了。“他们的设备是我们的五倍之多，也就是说，他们可同时拍摄30张Ｘ光照片，”鲍林写信告诉他的助手休斯说，“我认为我们必需毫不拖延地扩充我们的Ｘ射线实验室。” 鲍林又一次显示了强烈的竞争意识，他感到又要与布拉格展开一轮竞赛，而这次是为了更大的奖项而竞争。他不无忧虑地看到布拉格研究小组有很大的获胜机会。“我担心我们会输给英国对手，”鲍林写信给科里这么说，并在信中描述了佩鲁茨等人关于蛋白质结构的研究成果，“他们已经开始触及问题的核心，并正在想方设法取得突破……我认为他们取得了十分惊人的进展。”作力对策，鲍林要求科里改变研究的策略。他看到英国人利用蛋白质消化酶把蛋白质大分子分裂成中型分子——由大约26个氨基酸分子串成，这样大小的分子更加适宜于作Ｘ射线分析；他因而要求科里做同样的事情。科里有很强的敬业精神，他回信这样答复：“我急不可待地希望立即投入蛋白质研究，我想跟英国人好好地比一比。” 在余下的那些日子里，鲍林一家在英国过得很愉快。琳达和彼得喜欢他们的学校，同时也喜欢结交新朋友；克莱林在伦敦德雷根小学的拉丁语测验中取得了第一名，使大家吃了一惊。鲍林继续在牛津讲学，直到春季结束。5月份，他得到了洛克菲勒基金会批准给他70万美元资助的好消息。这笔资助用于他和比德尔的宏大合作项目：用分子生物学的方法开展蛋白质结构和其他问题的研究。6月份，他和爱娃在牛津跟孩子们和其他朋友一起庆祝他俩结婚25周年。 7月份，鲍林在阿姆斯特丹一次大型科学会议上报告了自己关于金属结构的新设想。他在黑板上写满了数据，然后自己躲到黑板后面讲话，逗得与会者开怀大笑。一天鲍林走在阿姆斯特丹的大街上，看到一个妇女的外套被夹在电车的门缝里，人被电车拖着跑。他立即从后面追上去，一面扶起这个妇女，一面猛敲车门，直到售票员停下车子松开她为止。鲍林表现出的天不怕地不怕的莽撞脾气给朋友们留下了难忘的印象。鲍林全家接着到了瑞士，后来又再到法国过了两个星期。在此期间鲍林从巴黎大学又得到了一个荣誉学位。 到他准备返回加州理工学院的时候，鲍林脑子里已充满了新的设想。离开美国的这段时间，使鲍林有机会与欧洲最优秀的科学家进行交流并受到启发，也使他能静下心来仔细思考一些问题。用价键理论处理金属键的思路，关于蛋白质螺旋结构的设想，均使他感到满意；对于与马利肯的辩论，他自己的感觉也挺不错；他的脑了里充满着其他设想，却急需验证。他在给科里的信中这么说：“我觉得这次花这么长时间出国访问是非常值得的，这里的环境有利于我思考问题并找出解决问题的办法。” 他访问欧洲的成果在他回到帕萨迪纳以后开始表现出来了。在几个月时间里，他写出了一系列论文，这些论文总结了他的互补性理论以及他在巴黎报告过的金属结构新理论；进一步论述了抗体的作用，氢化铀的结构，纤维性硫的稳定性，双价氧的键能以及血红蛋白的结构，Ｘ射线对果绳的作用，等等。文章所涉及的主题从科普性的“今日世界与化学”到专业性非常强的“类胡萝卜素的顺、反异构性”，分别发表在法国、德国、英国和美国的杂志上。从1948年到1949年的两年内，他发表文章的总数达到创记录的30篇。 在这些数目众多的论文中，有一组文章特别引人注目。这组文章报告了鲍林领导下的研究镰状细胞贫血症病因的小组所取得的成果。 得到这个结果并不容易。鲍林的看法是，变异的镰状细胞血红蛋白之所以在脱氧后发生结晶现象，是由于细胞的结构发生了变化。然而在很长的时间内，从医学博士转过来研究化学的青年学者依泰诺（鲍林在1946年秋季指派他研究这个问题）却找不出正常人的血红蛋白与镰状细胞贫血症患者的血红蛋白在结构上的重要区别，它们有相同的细胞重量，给出相同的酸基滴定曲线。由于镰状细胞血的供源很难找到，因此他的研究进度就更缓慢了。所有的镰状细胞贫血症患者均为非洲裔美国人，他们大多住在美国南部，在加州难得有几个病例。开始时鲍林和依泰诺尝试与洛杉矶黑人社区的医生达成协议，取得少量的血样；后来有一阵他们劝诱病人直接来加州理工学院供血，付给他们少量酬金。最后鲍林在路易斯安那的图莱恩大学找到一个医生，他可获得大量的这类血液并能满足鲍林的全部研究所需。 一旦拥有充裕的血源，鲍林就让依泰诺观察不同的化学药品对镰状细胞血红蛋白的影响。依泰诺的研究证实，氧气在发生镰状形变的过程中发挥著作用，在一定幅度内减少含氧量会加速红细胞的镰状化。在这一发现的基础上，他们提出了一种快速诊断镰状细胞病的测试法，鲍林和依泰诺还联合写出了第一篇有关这个课题的论文。依泰诺还证实，血液中加入一氧化碳后（一氧化碳会与血红蛋白不可逆转地结合在一起，从而阻止氧气的进入），能够防止红细胞出现镰状弯曲。根据鲍林的推测，所在的变异似乎都局限在血红蛋白分子里。 这个结果说明了为什么正常的血红蛋白和镰状细胞血红蛋白看起来那么相像。原来能够探测到的两者之间的区别只是分子所带电荷的微小差别。依泰诺把血红蛋白分子分割开来，发现这种差别局限在分子的蛋白质部分，即珠蛋白部分，而不发生在含铁的血质部分。对一个很大的分子来说，这只是一个微小的变化。需要利用极为敏感的探索工具才能进行深入的研究。 为了加快研究的进程，鲍林在1947年秋季吸收了另一个博士后研究者加入该项目，他的名字叫辛格。辛格在大分子的物化研究方面比依泰诺更有经验，他还懂得怎样使用一种叫做泰氏仪的新型仪器。这种仪器是战前由瑞典化学家泰赛列斯发明的，它利用分子的电学性质把蛋白质从混合体中分离出来。人们知道，每个蛋白质分子的表面都携带着一组确定的电荷。泰赛列斯据此发明了一种仪器，蛋白质溶液放置在仪器的玻璃试管的中部，试管置于电场之中，一头为正极，另一头为负极。根据各种不同的因素，特别是按照蛋白质分子表面携带的不同的电荷组合，溶液中的蛋白质分子将以不同的方式和速度，被吸引到正极或负极上去。这是一种精巧、轻柔而又精确性很高的分高蛋白质混合液的方法，在分离过程中蛋白质分子不会受到任何损害。在大战期间泰氏仪还很少，而且在市场上买不到，鲍林请斯托特范特为加州理工学院专门制作了一台。 当鲍林在英国访问的时候，理工学院的泰氏仪已经安装就绪并可实际使用了。辛格和依泰诺试着利用它来分离镰状细胞和正常的血红蛋白，最后终于发现了两者之间的区别。镰状细胞血红蛋白分子比正常分子以更快的速度趋向电场的负极，看起来在正常的pH值下，镰状细胞分子带有3个额外的单位正电荷。这个结果明确显示了一个事实：镰状细胞贫血症患者血液中的血红蛋白分子与正常人血液中的同类分子有着重要的区别。鲍林原先的推测是正确的。 这个结果令人十分惊讶：仅一种分子所带的电荷发生细微变化，就可使健康人患上致命的疾病。在为这项研究所写的第一篇重要论文中，鲍林把这种奇异的特性醒目地写进了论文的标题：“镰状细胞贫血症，一种分子型疾病”，这篇论文于1949年秋季正式发表。尽管在此之前已有人用比较宽泛的语言从分子层面上论述过疾病的病因，但像鲍林研究组这样具体展示疾病的分子变异基础的，还是第一次。此后，辛格和依泰诺继续深入进行这一项研究。处于镰状细胞贫血症中间阶段的患者称为有“镰状细胞贫血性状”，比重症病人的症状要轻。依泰诺和辛格通过实验证实，这类病人的血液中含有正常血红蛋白和镰状细胞血红蛋白的混合体。对正常人、镰状细胞贫血性状患者和镰状细胞贫血症患者的家族关系进行分析的结果显示，这种病是按照孟德尔①式遗传的。遗传疾病的镰状细胞基因由两条等位基因组成，即有两个变异体，分别来自父母亲。镰状细胞贫血性状患者携带一条带病的等位基因。即一个变异体；而重症病人携带两条带病的等位基因。 ①孟德尔（Gregor Mendel，1822—1884），奥地利遗传学家，孟德尔学派创始人，原为天主教神父，发现遗传基因原理（1865），总结出分离定律和独立分配定律，奠定了遗传学的数学基础。 这样，鲍林研究组确定了疾病的根源在于某类特定分子的变异，并把这种变异与基因学说紧密联系了起来。他们的研究成果成为医学和分子生物学发展史上的里程碑。这一成果证实了鲍林的看法：弄清楚蛋白质分子所在的那个未知的黑暗区域的情况是十分重要的，这就吸引了整整一代医学科研人员从分子层面上来进行疾病的研究。这一成果有力地支持了鲍林关于医药研究必须建立在现代化学方法基础上的观点，展示了对遗传性疾病新的研究前景。他们的研究成果还开创了异常血红蛋白研究工作的新时期，这类研究此后延续了多年并取得了丰硕的成果。最后，他们的成果又一次提高了鲍林的地位，特别是他在医学界的地位。