LINUS CARL PAULING

February 28, 1901-August 19, 1994

BY JACK D. DUNITZ

LINUS CARL PAULING was born in Portland, Oregon, on February 28, 1901, and died at his ranch at Big Sur, California, on August 19, 1994. In 1922 he married Ava Helen Miller (died 1981), who bore him four children: Linus Carl, Peter Jeffress, Linda Helen (Kamb), and Edward Crellin.

Pauling is widely considered the greatest chemist of this century. Most scientists create a niche for themselves, an area where they feel secure, but Pauling had an enormously wide range of scientific interests: quantum mechanics, crystallography, mineralogy, structural chemistry, anesthesia, immunology, medicine, evolution. In all these fields and especially in the border regions between them, he saw where the problems lay, and, backed by his speedy assimilation of the essential facts and by his prodigious memory, he made distinctive and decisive contributions. He is best known, perhaps, for his insights into chemical bonding, for the discovery of the principal elements of protein secondary structure, the alpha-helix and the beta-sheet, and for the first identification of a molecular disease (sickle-cell anemia), but there are a multitude of other important contri-

This biographical memoir was prepared for publication by both The Royal Society of London and the National Academy of Sciences of the United States of America.



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--> LINUS CARL PAULING February 28, 1901-August 19, 1994 BY JACK D. DUNITZ LINUS CARL PAULING was born in Portland, Oregon, on February 28, 1901, and died at his ranch at Big Sur, California, on August 19, 1994. In 1922 he married Ava Helen Miller (died 1981), who bore him four children: Linus Carl, Peter Jeffress, Linda Helen (Kamb), and Edward Crellin. Pauling is widely considered the greatest chemist of this century. Most scientists create a niche for themselves, an area where they feel secure, but Pauling had an enormously wide range of scientific interests: quantum mechanics, crystallography, mineralogy, structural chemistry, anesthesia, immunology, medicine, evolution. In all these fields and especially in the border regions between them, he saw where the problems lay, and, backed by his speedy assimilation of the essential facts and by his prodigious memory, he made distinctive and decisive contributions. He is best known, perhaps, for his insights into chemical bonding, for the discovery of the principal elements of protein secondary structure, the alpha-helix and the beta-sheet, and for the first identification of a molecular disease (sickle-cell anemia), but there are a multitude of other important contri- This biographical memoir was prepared for publication by both The Royal Society of London and the National Academy of Sciences of the United States of America.

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--> butions. Pauling was one of the founders of molecular biology in the true sense of the term. For these achievements he was awarded the 1954 Nobel Prize in chemistry. But Pauling was famous not only in the world of science. In the second half of his life he devoted his time and energy mainly to questions of health and the necessity to eliminate the possibility of war in the nuclear age. His active opposition to nuclear testing brought him political persecution in his own country, but he was finally influential in bringing about the 1963 international treaty banning atmospheric tests. With the award of the 1962 Nobel Peace Prize, Pauling became the first person to win two unshared Nobel Prizes (Marie Curie won one and shared another with her husband). Pauling's name is probably best known among the general public through his advocacy, backed by personal example, of large doses of ascorbic acid (vitamin C) as a dietary supplement to promote general health and prevent (or at least reduce the severity of) such ailments as the common cold and cancer. Indeed, Albert Einstein and Linus Pauling are probably the only scientists in our century whose names are known to every radio listener, television viewer, or newspaper reader. EARLY YEARS Pauling was the first child of Herman Pauling, son of German immigrants, and Lucy Isabelle (Darling) Pauling, descended from pre-revolutionary Irish stock. There were two younger daughters: Pauline Darling (born 1902) and Lucile (born 1904). Herman Pauling worked for a time as a traveling salesman for a medical supply company and moved in 1905 to Condon, Oregon, where he opened his own drugstore. It was in this new boom town in the arid country east of the coastal range that Pauling had his first schooling. He learned to read early and started to devour books. In 1910

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--> the family moved back to Portland, where his father wrote a letter to The Oregonian, a local newspaper, asking for advice about suitable reading matter for his nine-year-old son, who had already read the Bible and Darwin's theory of evolution. We do not know the replies, but Pauling later confessed that one of his favorites was the Encyclopaedia Britannica. Soon tragedy struck. In June of that year Herman Pauling died after a sudden illness, probably a perforated stomach ulcer with attendant peritonitis, leaving his family in a situation with which the young mother could not adequately cope. Linus did well at school. He collected insects and minerals and read omnivorously. He made up his mind to become a chemist in 1914, when a fellow student, Lloyd A. Jeffress, showed him some chemical experiments he had set up at home. With the reluctant approval of his mother he left school in 1917 without a diploma and entered Oregon Agricultural College at Corvallis as a chemical engineering major, but after two years his mother wanted him to leave college to earn money for the support of the family. He must have impressed his teachers, for in 1919, after a summer working as a road-paving inspector for the State of Oregon, he was offered a full-time post as instructor in qualitative analysis in the chemistry department. The eighteen-year-old teacher felt the need to read current chemical journals and came across the recently published papers of Gilbert Newton Lewis and Irving Langmuir on the electronic structure of molecules. Having understood the new ideas, the “boy professor" introduced them to his elders by giving a seminar on the nature of the chemical bond. Thus was sparked the "strong desire to understand the physical and chemical properties of substances in relation to the structure of the atoms and molecules of which they are

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--> composed," which determined the course of Pauling's long life. The following year Pauling resumed his student status and graduated in 1922 with a B.Sc. degree. In his final year he was given another opportunity to teach, this time an introductory chemistry course for young women students of home economics. This new teaching episode also had important consequences for his future. One of the students was Ava Helen Miller, who became his wife in a marriage that lasted almost sixty years. PASADENA Pauling came to the California Institute of Technology as a graduate student in 1922 and remained there for more than forty years. He chose Caltech because he could obtain a doctorate there in three years (Harvard required six) and because Arthur Amos Noyes offered him a modest stipend as part-time instructor. It was a fortunate choice both for Pauling and for Caltech. As he wrote towards the end of his life, "Years later ... I realized that there was no place in the world in 1922 that would have prepared me in a better way for my career as a scientist" (1994). When he arrived the newly established institute consisted largely of the hopes of its three founders, the astronomer George Ellery Hale, the physicist Robert A. Millikan, and the physical chemist Arthur Amos Noyes. There were three buildings and eighteen faculty members. When he left, Caltech had developed into one of the major centers of scientific research in the world. In chemistry Pauling was the prime mover in this development. Indeed, for many young chemists of my generation, Caltech meant Pauling. Pauling's doctoral work was on the determination of crystal structures by X-ray diffraction analysis under the direction of Roscoe Gilkey Dickinson (1894-1945), who had obtained

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--> his Ph.D. only two years earlier (he was the first person to receive a Ph.D. from Caltech). By a happy chance, Ralph W. G. Wyckoff (1897-1994), one of the pioneers of X-ray analysis, had spent the year before Pauling's arrival at Caltech and had taught Dickinson the method of using Laue photographic data (white radiation, stationary crystal; a method that fell into disuse but has newly been revived in connection with rapid data collection with synchrotron radiation sources). Wyckoff taught Dickinson, and Dickinson taught Pauling, who soon succeeded in determining the crystal structures of the mineral molybdenite MoS2 (Dickinson and Pauling, 1923) and the intermetallic compound MgSn (1923). By the time he graduated in 1925 he had published twelve papers, most on inorganic crystal structures, but including one with Peter Debye (1884-1966) on dilute ionic solutions (Debye and Pauling, 1925) and one with Richard Tolman (1881-1948) on the entropy of supercooled liquids at 0 K (Pauling and Tolman, 1925). Pauling had already made up for his lack of formal training in physics and mathematics. He was familiar with the quantum theory of Planck and Bohr and was ready for the conceptual revolution that was soon to take place in Europe. Noyes obtained one of the newly established Guggenheim fellowships for the rising star and sent him and his young wife off to the Institute of Theoretical Physics, directed by Arnold Sommerfeld (1868-1951), in Munich. They arrived in April 1926, just as the Bohr-Sommerfeld model was being displaced by the "new" quantum mechanics. It was an exciting time, and Pauling knew he was lucky to be there at one of the centers. He concentrated on learning as much as he could about the new theoretical physics at Sommerfeld's institute. Pauling had been regarded, and probably also regarded himself, as intellectually outstanding among his fellow students at Oregon and even at Caltech;

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--> however, he must have become aware of his limitations during his stay in Europe. The new theories were being made by men of his own generation. Wolfgang Pauli (1900-58), Werner Heisenberg (1901-76), and Paul Dirac (1902-84) were all born within a year of Pauling and were more than a match for him in physical insight, mathematical ability, and philosophical depth. Pauling was not an outstanding theoretical physicist and was probably not particularly interested in problems such as the deep interpretation of quantum mechanics or the philosophical implications of the uncertainty principle. On the other hand, he was the only chemist at Sommerfeld's institute and saw at once that the new physics was destined to provide the theoretical basis for understanding the structure and behavior of molecules. The year in Europe was to have a decisive influence on Pauling's scientific development. In addition to Munich, he visited Copenhagen in the spring of 1927 and then spent the summer in Zurich. In Copenhagen it was not Bohr but Samuel A. Goudsmit (1902-78) who influenced Pauling (they later collaborated in writing The Structure of Line Spectra, New York: McGraw-Hill, 1930), and in Zurich it was neither Debye nor Schrödinger but the two young assistants, Walter Heitler (1904-81) and Fritz London (1900-54), who were working on their quantum-mechanical model of the hydrogen molecule in which the two electrons are imagined to "exchange" their roles in the wave function—an example of the "resonance" concept that Pauling was soon to exploit so successfully. One immediate result of the stay in Munich was Pauling's (1927) first paper in the Proceedings of the Royal Society of London, submitted by Sommerfeld himself. Pauling was eager to apply the new wave mechanics to calculate properties of many-electron atoms and he found a way of doing

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--> this by using hydrogen-like single-electron wave functions for the outer electrons with effective nuclear charges based on empirical screening constants for the inner electrons. THE NATURE OF THE CHEMICAL BOND In 1927 Pauling returned to Caltech as assistant professor of theoretical chemistry. The next twelve years produced the remarkable series of papers that established his worldwide reputation. His abilities were quickly recognized through promotions (to associate professor, 1929; full professor, 1931), through awards (Langmuir Prize, 1931), through election to the National Academy of Sciences (1933), and through visiting lectureships, especially the Baker lectureship at Cornell in 1937-38. Through his writings and lectures, Pauling established himself as the founder and master of what might be called structural chemistry—a new way of looking at molecules and crystals. Pauling's way was first to establish a solid and extensive collection of data. By means of X-ray crystallography, gasphase electron diffraction (installed after Pauling's 1930 visit to Europe, where he learned about Hermann Mark's pioneering studies), and infrared, Raman, and ultraviolet spectroscopy, interatomic distances and angles were established for hundreds of crystals and molecules. Thermochemical information was already available. The first task of theory, as Pauling saw it, was to provide a basis to explain the known metric and energetic facts about molecules, and only then to lead to prediction of new facts. At this stage of his development Pauling was attracting many talented co-workers, undergraduates, graduate students, and postdoctoral fellows, and their names read like a Who's Who in the structural chemistry of the period: J. H. Sturdivant, J. L. Hoard, J. Sherman, L. O. Brockway, D. M. Yost, G. W. Wheland, M. L. Huggins, L. E. Sutton, E. B. Wilson, S. H. Bauer, C. D.

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--> Coryell, V. Schomaker, and others. Here are the major achievements. Pauling's ionic radii: Once the structures of simple inorganic crystals began to be established it was soon seen that the observed interatomic distances were consistent with approximate additivity of characteristic radii associated with the various cations and anions. Among the several sets that have been proposed, Pauling's are not merely designed to reproduce the observations but, typical for him, are derived from a mixture of approximate quantum mechanics (using screening constants) and experimental data. His values, derived almost seventy years ago, are still in common use, and the same can be said for the sets of covalent radii and nonbonded (van de Waals) radii that he introduced. Pauling's rules: Whereas simple ionic substances, such as the alkali halides, are limited in the types of crystal structure they can adopt, the possibilities open to more complex substances, such as mica, KA13Si3O10(OH)2, may appear to be immense. Pauling (1929) formulated a set of rules about the stability of such structures, which proved enormously successful in testing the correctness of proposed structures and in predicting unknown ones. As Pauling himself remarked, these rules are neither rigorous in their derivation nor universal in their application; they were obtained in part by induction from known structures and in part from theoretical considerations. His second rule states essentially that electrostatic lines of force stretch only between nearest neighbors. In the meantime, as structural knowledge has accumulated, this rule has been modified by various authors to relate bond strengths to interatomic distances, but it seems fair to say that it is still the basis for the systematic description of inorganic structures. W. L. Bragg, who may

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--> have felt somewhat beaten to the post by the publication of these rules, wrote (1937): "The rule (the second one) appears simple, but it is surprising what rigorous conditions it imposes upon the geometrical configuration of a silicate... To sum up, these rules are the basis for the stereochemistry of minerals." Quantum chemistry: In 1927 Ø. Burrau solved the Schrödinger equation for the hydrogen molecule ion H2+ in elliptic coordinates and obtained values for the interatomic distance and bonding energy in good agreement with experiment. Burrau's wave function fails, however, to yield much physical insight into the stability of the system. Soon afterwards, Pauling (1928) pointed out that although an approximate perturbation treatment would not provide any new information, it would be useful to know how well it performed: "For perturbation methods can be applied to many systems for which the wave equation cannot be accurately solved .... ." Pauling first showed that the classical interaction of a ground state hydrogen atom and a proton is repulsive at all distances. However, if the electron is not localized on one of the atoms, and the wave function is taken as a linear combination of the two ground state atomic wave functions, then the interaction energy has a pronounced minimum at a distance of about 2 a.u. This was the first example of what has come to be known as the method of Linear Combination of Atomic Orbitals (LCAO). For the hydrogen-molecule ion, the LCAO dissociation energy is only about 60% of the correct value, but the model provides insight into the source of the bonding and can easily be extended to more complex systems. In fact, the LCAO method is the basis of modern molecular orbital theory. A few months earlier Heitler and London had published their calculation for the hydrogen molecule. This was too

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--> complicated for an exact solution, and their method also rested on a perturbation model, a combination of atomic wave functions in which the two electrons, with opposite spins, change places. More generally, the energy of the electron-pair bond could now be attributed to "the resonance energy corresponding to the interchange of the two electrons between the two atomic orbitals." As developed by Pauling and independently by John C. Slater (1900-76), the Heitler-London-Slater-Pauling (HLSP) or Valence Bond model associates each conventional covalent bond with an electron pair in a localized orbital and then considers all ways in which these electrons can "exchange." Much has been made of Pauling's preference for Valence Bond (VB) theory over Molecular Orbital (MO) theory. The latter, as developed by Fritz Hund (born 1896), Erich Hückel (1896-1980), and Robert S. Mulliken (1896-1986), works in terms of orbitals extended over the entire molecule, orders these orbitals according to their estimated energies, and assigns two electrons with opposite spin to each of the bonding orbitals. Electronic excited states correspond to promotion of one or more electrons from bonding to antibonding orbitals. Nowadays, MO theory has proved itself more amenable to computer calculations for multicenter molecules, but in the early days, when only hand calculations were possible, it was largely a matter of taste. The main appeal of the MO model was then to spectroscopists. Chemists, in general, were less comfortable with the idea of pouring electrons into a ready-made framework of nuclei. It was more appealing to build molecules up from individual atoms linked by electron-pair bonds. The VB picture was more easily related to the chemist's conventional structural formulas. Both models are, of course, drastic simplifications, and it was soon recognized that when appropriate correction terms are added and the proper transformations

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--> are made they become equivalent. In particular, the MO method in its simplest form ignores electron-electron interactions, while the VB method overestimates them. Pauling was fully acquainted with early MO theory—there is at least one important paper (Wheland and Pauling, 1935) on the theory of aromatic substitution. But he clearly preferred his own simplified versions of VB theory and soon became a master of combining them with the empirical facts of chemistry. A remarkable series of papers entitled "The Nature of the Chemical Bond" formed the basis for his later book with the same title. In the very first paper Pauling (1931) set out his program of developing simple quantum mechanical treatments to provide information about "the relative strengths of bonds formed by different atoms, the angles between bonds, free rotation, or lack of free rotation about bond axes, the relation between the quantum numbers of bonding electrons and the number and spatial arrangements of bonds, and so on. A complete theory of the magnetic moments of molecules and complex ions is also developed, and it is shown that for many compounds involving elements of the transition group this theory together with the rules of electron pair bonds leads to a unique assignment of electron structures as well as a definite determination of the type of bonds involved." To a large extent Pauling developed his own language to describe his new concepts, and of the many new terms introduced, three seem indelibly associated with his name: hybridization, resonance, and eletronegativity. Only the first of these truly originates from him. In the first paper of the series Pauling took up the idea of spatially directed bonds. By a generalization of the Heitler-London model for hydrogen, a normal chemical bond can be associated with the spin pairing of two electrons, one from each of the two atoms. While an s orbital is spherically symmetri-

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--> resigned from the American Chemical Society as well. The move to Santa Barbara was not a success. He turned to theoretical physics, but his close-packed spheron theory of the atomic nucleus met with little acceptance. He became engaged in actual and threatened libel suits. He moved briefly to the University of California at San Diego (1967-69) and then on to Stanford University (1969-72), where he was closer to his ranch at Big Sur, but he had no stable position in which to continue his planned research into "orthomolecular" psychiatric therapy. Meanwhile, he was deeply unhappy about the American involvement in Vietnam and about American politics in general. One consolation was that after passing his sixty-fifth birthday Pauling's health took a sudden turn for the better. Thanks to Dr. Addis's unconventional low-protein diet, he had recovered well from the kidney disease that had laid him low in his forties, but he had always suffered from severe colds several times a year. In 1966, following a suggestion from Dr. Irwin Stone, the Paulings began to take three grams of ascorbic acid per day each. Almost immediately they felt livelier and healthier. Over the next few years the colds that had plagued him all his life became less severe and less frequent. This experience made Pauling a believer in the health benefits of large daily amounts of vitamin C. It was not long before he was enthusiastically promulgating this belief in lectures and writings, which, not too surprisingly, brought on him the displeasure of the American medical establishment. After all, the then recommended daily allowance (RDA) of vitamin C was 45 mg; it was well known that there was no known cure for the common cold, and, in particular, previous studies had shown conclusively that vitamin C had no effect. Nevertheless, the NAS Subcommittee on Laboratory Animal Nutrition was then recommending daily intakes around 100 times that of the human RDA

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--> (adjusted for body weight) to keep laboratory primates in optimal health. In his 1970 book Vitamin C and the Common Cold, Pauling gave evolutionary arguments why much larger amounts of vitamin C than the RDA may be conducive to optimal health. He cited studies supporting its efficacy in preventing colds or at least in lessening their severity. He criticized studies that claimed the opposite and he argued that since vitamin C is not a drug but a nutrient there is no reason why a large daily intake should be harmful. Pauling's arguments did not win the approval of the medical profession but they caught on with the general public. The book rapidly became a best seller. As a result, in America and later in other countries, millions of people have been persuaded that a daily intake of 1-2 g of ascorbic acid has a beneficial effect on health and well being, essentially agreeing with Pauling that “we may make use of ascorbic acid for improving health in the ways indicated by experience, even though a detailed understanding of the mechanisms of its action has not yet been obtained." One result of the book was a collaboration with a Scottish surgeon, Ewan Cameron, from Vale of Leven, who had observed beneficial effects of high doses of vitamin C in treating terminal cancer patients. Cameron thought that vitamin C might be involved in strengthening the intracellular mucopolysaccharide hyaluronic acid by helping to inhibit the action of the enzyme hyaluronidase produced by invasive cancerous cells. A paper by Cameron and Pauling (1973) advocating vitamin C therapy in cancer was submitted to the Proceedings of the National Academy of Sciences (PNAS), which, in an unprecedented move, rejected the paper (it was then published in the specialist journal Oncology). During the next few years Cameron continued his trials. Since a double-blind trial was ethically unacceptable, he compared

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--> results obtained with one hundred ascorbate-treated terminal patients and one thousand other cases, ten controls for each patient, matched as closely as possible, and found that the ascorbate-treated patients lived longer and felt better subjectively. A paper describing these results was eventually published in PNAS (Cameron and Pauling, 1976) but only after long arguments with referees. The Cameron-Pauling collaboration culminated in their 1979 book Cancer and Vitamin C, which was again more popular with the public than the medical profession, which continued to regard claims about the effectiveness of vitamin C in treating or preventing cancer as quackery. But by this time several important changes had occurred in Pauling's life. At Stanford Pauling's demands for more laboratory space for his orthomolecular medicine studies had been turned down. A solution was found by a younger colleague, Arthur B. Robinson, who had left a tenured position at San Diego to work with Pauling at Stanford. Instead of working in cramped quarters at the university they would set up their own research institute nearby. A building was rented, initial financial help was forthcoming, and the Institute for Orthomolecular Medicine was founded in 1973. Once the initial funding ran out the institute found itself in financial straits. Soon it was renamed the Linus Pauling Institute of Science and Medicine with Pauling as president. By this change, it was hoped, fund-raising possibilities would be improved—a hope that proved illusory. Since Pauling was frequently away on travels and in any case disliked administration, Robinson took over in 1975, but the fiscal problems of the institute dragged on for several years until support began to be provided by private foundations and individual donations. Personal and scientific difficulties between Robinson and Pauling led to Robinson's dismissal in 1979 and to lawsuits that dragged on for years. Meanwhile, Pauling continued to

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--> defend his unorthodox views and became once again a controversial figure, regarded by some as a crackpot, by others as a sage. In 1986 he wrote another popular book How to Live Longer and Feel Better, which, based on his own experiences, gave advice about how to cope with aging. In July 1976 Ava Helen underwent surgery for stomach cancer. Instead of post-operative chemotherapy or radiation treatment she adopted vitamin C therapy to the tune of 10 g per day. She was soon well enough to accompany Pauling on his various travels, but she finally succumbed five years later in December 1981. Pauling continued to travel, appear on television, write, and receive honors—his energy seemed unabated. When quasi-crystals with forbidden fivefold symmetry were discovered in 1984 Pauling took a contrary position and argued that the fivefold symmetry seen in Al/Mn alloys resulted merely from twinning of cubic crystallites (1985). He was probably wrong, but the resulting controversy was nevertheless useful in forcing the proponents of quasi-crystals to seek better evidence for their view. He even became reconciled with Caltech, where his eighty-fifth and ninetieth birthdays were marked by special symposia in his honor. In 1991 he was diagnosed with cancer. Surgery brought temporary relief, and megadoses of vitamin C kept up his spirits. He spent his last months at the ranch at Big Sur and died there on August 19, 1994. In the meantime, the medical establishment is no longer so totally dismissive of Pauling's views about possible therapeutic benefits of vitamin C on the common cold and on cancer. A recent review of several studies concludes that although supplemental vitamin C does not decrease the incidence of the common cold it does diminish the duration and severity of symptoms (Hemila, 1992). This review also states that the level of vitamin C intake derived from a

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--> normal or balanced diet may be insufficient for optimal body function and that the substance is safe even in large amounts. The connection between vitamin C and cancer has also become a respectable topic of discussion. It was the subject of a conference organized by the National Cancer Institute in Washington, D.C., in 1990. Vitamins C and E (and other anti-oxidants) inhibit the endogenous formation of N-nitroso compounds in animals and humans (Bartsch, Ohshima, and Pignatelli, 1988). Such compounds are known to be carcinogenic in animals. Conclusive proof that they are dangerous at the levels naturally present in man is lacking, but the evidence seems suggestive. Thus, although the effectiveness of vitamin C in treating cancers may still be debatable, there is good reason to believe that it has at least an important preventative role. The final word about the effect of large doses of vitamin C on health has still to be said. If you have a full, healthy diet rich with fruit, grains, and fresh vegetables, then you probably do not need supplemental vitamins and minerals. But in the modern world many people have, and may even prefer, an unhealthy diet. For them vitamin supplements are probably beneficial. After all, Pauling not only recommended large doses of vitamin C but also advised people to stop smoking, eat less, and cut down on sucrose. PAULING THE MAN Pauling lived a long and productive life. As scientist, through his writings and personal impact, he influenced several generations of chemists and biologists. As political activist he challenged the political and military establishment of the United States and helped to change them. As health crusader he took on the medical establishment and persuaded millions of people to eat supplemental vitamins.

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--> He could be very persuasive indeed. His lectures were spellbinding, and he had a characteristically simple and direct literary style. I remember his lectures at Oxford in early 1948. The lecture hall was too small to hold all who wished to attend; there was standing room only. He told those of us who had never studied electrostatics to go home and read Sir James Jeans's book on that subject before coming to his lectures on chemical bonding. I had never studied electrostatics but I stayed, spellbound. I had never heard anyone quite like him, with his jokes, relaxed manner, seraphic smile, slide-rule calculations, and spontaneous flow of ideas (only much later did I realize that much of that apparent spontaneity was carefully studied). He had great histrionic skills. Vain? Conceited? Pauling was certainly aware of his own intellectual superiority, but he could be patient in dealing with the slowness of the slow witted. On the whole he was fairly tolerant of young, insecure seminar speakers, although, as I remember, he could also be intimidating at times. I am referring here to Pauling in middle age; I am told he became more intolerant in his later years. Political harassment during and after the McCarthy era must have taken its toll. Ambitious? Self-centered? Undoubtedly. Without these traits he would not have been able to accomplish as much as he did. But he often had a merry twinkle in his eyes and could be very charming, both as a public personality and in private. In personal matters he kept most people at a distance. I believe he was basically rather shy. When he talked about science or politics or anything that caught his interest there was no stopping him. He read widely and was extremely knowledgeable in many areas-a result of having pored over the Encyclopaedia Britannica in his youth? In conversation one sometimes sensed a faraway look in his eyes; one felt

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--> that he was already thinking about something else. Probably he was, and, indeed, he was a formidable thinker, both at the problem-solving level and about fundamentals. With his prodigious memory he could call up facts and derivations, what so-and-so had written in 1928, the unit cell dimensions of an obscure mineral, the standard heat of formation of ethane; and he had a remarkable capacity to visualize complex three-dimensional structures. I once asked him why he had never discussed the application of group theory to problems of chemical bonding. "Jack," he replied, "if you need group theory to solve that sort of problem then you're in the wrong line of business." In addition to his Nobel Prizes Pauling was awarded dozens of honors and distinctions, including honorary doctorates from Oregon State College, Brooklyn Polytechnic Institute, Reed College, and the Universities of Chicago, Princeton, Yale, Cambridge, London, Oxford, Paris, Toulouse, Montepellier, Lyon, Liege, Humboldt (Berlin), Melbourne, York (Toronto), New Brunswick, and Warsaw. His election to membership in the National Academy of Sciences, Royal Society of London, Academie Frangaise des Sciences, and Akademiya Nauk SSR may be specially mentioned. His name will be remembered as long as there is a science of chemistry. I HAVE LEARNED MUCH about Pauling's life from the excellent biography by Tom Hager (1995) and am grateful for information and advice from many friends and colleagues, among them David Craig, Durward W. J. Cruickshank, Albert Eschenmoser, Edgar Heilbronner, Barclay and Linda Pauling Kamb, Paul Kleihues, Alan Mackay, Peter J. Pauling, Alexander Rich,John D. Roberts, and Verner Schomaker.

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--> REFERENCES Bartsch, H., H. Ohshima, and B. Pignatelli. 1988. Inhibitors of endogenous nitrosation. Mechanisms and implications in human cancer prevention. Mutat. Res. 202:307-24. Bernal, J. D. 1939. Structure of proteins. Nature (London) 143:663-67. Bragg, W. L. 1937. Atomic Structure of Minerals. Ithaca, N.Y.: Cornell University Press. Bragg, W. H., J. C. Kendrew, and M. F. Perutz. 1950. Polypeptide chain configurations in crystalline proteins. Proc. R. Soc. Lond. A203:321-57. Cameron, E., and L. Pauling. 1973. Ascorbic acid and the glycosaminoglycans: An orthomolecular approach to cancer and other diseases. Oncology 27:181-92. Cameron, E., and L. Pauling. 1976. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc. Natl. Acad. Sci. U.S.A. 73:3685-89. Debye, P., and L. Pauling. 1925. The inter-ionic attraction theory of ionized solutes. IV. The influence of variation of dielectric constant on the limiting law for small concentrations. J. Am. Chem. Soc. 47:2129-34. Dickinson, R. G., and L. Pauling. 1923. The crystal structure of molybdenite. J. Am. Chem. Soc. 45:1466-71. Hager, T. 1995. Force of Nature: The Life of Linus Pauling. New York: Simon & Schuster. Hemila, H. 1992. Vitamin C and the common cold. Br. J. Nutr. 67:316. Jencks, W. P. 1969. Catalysis in Chemistry and Enzymology. New York: McGraw-Hill. Kauffman, G. B., and L. M. Kauffman. 1996. An interview with Linus Pauling. J Chem. Educ. 73:29-32. Mirsky, A. E., and L. Pauling. 1936. On the structure of native, denatured, and coagulated proteins. Proc. Natl. Acad. Sci. U.S.A. 22:439-47. Pauling, L. 1923. The crystal structure of magnesium stannide. J. Am. Chem. Soc. 45:2777-80. Pauling, L. 1927. The theoretical prediction of the physical properties of many-electron atoms and ions: Mole Refraction, diamag-

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--> Pauling, L., R. B. Corey, and H. R. Branson. 1951. The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chains. Proc. Natl. Acad. Sci. U.S.A. 37:205-10. Pauling, L., and C. D. Coryell. 1936. The magnetic properties and structure of hemoglobin, oxyhemoglobin and carbonmonoxyhemoglobin. Proc. Natl. Acad. Sci. U.S.A. 22:210-16. Pauling, L., and M. Delbrück. 1940. The nature of intermolecular forces operative in biological processes. Science 92:77-79. Pauling, L., H. A. Itano, S. J. Singer, and I. C. Wells. 1949. Sickle cell anemia, a molecular disease. Science 110:543-48. Pauling, L., and R. C. Tolman. 1925. The entropy of supercooled liquids at the absolute zero. J. Am. Chem. Soc. 47:2148-56. Pauling, P. 1973. DNA-The race that never was? New Sci. 58:558-60. Perutz, M. G. 1987. I wish I'd made you angry earlier. Scientist, (Feb. 23):19. Sakharov, A. 1990. Memoirs (English translation by R. Laurie). New York: Knopf. Wheland, G. W., and L. Pauling. 1935. A quantum mechanical discussion of orientation of substituents in aromatic molecules. J. Am. Chem. Soc. 57:2086-95. Zuckerkandl, E., and L. Pauling. 1962. Molecular disease, evolution and genetic heterogeneity. In Horizons in Biochemistry, eds. M. Kasha and P. Pullman, pp. 189-225. New York: Academic Press. BIBLIOGRAPHY A complete bibliography, by permission of the Linus Pauling Institute, is available from The Royal Society, London.

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