Linus Carl Pauling Biography - Nobel Prize Winner (1954)

Linus Carl Pauling (February 28, 1901 – August 19, 1994) was an American quantum chemist and biochemist, widely regarded as the premier chemist of the twentieth century. Pauling was a pioneer in the application of quantum mechanics to chemistry (quantum mechanics can, in principle, describe all of chemistry and molecular biology), and in 1954 was awarded the Nobel Prize in chemistry for his work describing the nature of chemical bonds. He also made important contributions to crystal and protein structure determination, and was one of the founders of molecular biology. Pauling is noted as a versatile scholar for his expertise in inorganic chemistry, organic chemistry, metallurgy, immunology, anesthesiology, psychology, debate, radioactive decay, and the aftermath of nuclear weapons, in addition to quantum mechanics and molecular biology.

Pauling received the Nobel Peace Prize in 1962 for his campaign against above-ground nuclear testing, becoming the only person in history to individually receive two Nobel Prizes (Marie Curie won Nobel Prizes in physics and chemistry, but shared the former and won the latter individually; John Bardeen won two Nobel Prizes in the field of physics, but both were shared; Frederick Sanger won two Nobel Prizes in chemistry, but one was shared).

Later in life, he became an advocate for regular consumption of massive doses of Vitamin C, which is still regarded as unorthodox by conventional medicine.

Early life
Pauling was born in Portland, Oregon to Herman Henry William Pauling (1876-1910) of Concordia, Missouri; and Lucy Isabelle Darling (1881-1926) of Lonerock, Oregon. Herman was an unsuccessful druggist who moved his family to and from a number of different cities in Oregon from 1903 to 1909, finally returning to Portland that year. Herman died in 1910 of a perforated ulcer, and Isabelle was left to care for Linus and two younger siblings: Pauline Pauling (1901-2003) who married Thomas Joseph Ney (1881-1963) of Millville, New Jersey; and Frances Lucille Pauling (1904-?).

Pauling was a voracious reader as a child, and at one point his father wrote a letter to a local paper inviting suggestions of additional books that would occupy his time. A friend, Lloyd Jeffress, had a small chemistry laboratory in his bedroom when Pauling was in grammar school, and Jeffress' laboratory experiments inspired Pauling to plan to become a chemical engineer.

In high school, Pauling continued to experiment in chemistry, borrowing much of the equipment and materials from an abandoned steel company near which his grandfather worked as a night watchman.

Pauling failed to take some required American history courses and did not qualify for his high school diploma. The school awarded him the diploma 45 years later  only after he had won two Nobel Prizes.

College and university

Pauling graduated from Oregon Agricultural College in 1922.In 1917, Pauling entered the Oregon Agricultural College (OAC) in Corvallis, now Oregon State University. Because of financial needs, he had to work full-time while attending a full schedule of classes. After his second year, he planned to take a job in Portland to help support his mother, but the college offered him a position teaching quantitative analysis (a course Pauling had just finished taking as a student). This allowed him to continue his studies at OAC.

In his last two years at OAC, Pauling became aware of the work of Gilbert N. Lewis and Irving Langmuir on the electronic structure of atoms and their bonding to form molecules. He decided to focus his research on how the physical and chemical properties of substances are related to the structure of the atoms of which they are composed, becoming one of the founders of the new science of quantum chemistry.

In 1922, Pauling graduated from OAC and went to graduate school at the California Institute of Technology ("Caltech") in Pasadena, California under the guidance of Roscoe Gilkey Dickinson. His graduate research involved the use of X-ray diffraction to determine crystal structure. He published seven papers on the crystal structure of minerals while he was at Caltech. He received his Ph. D. degree in physical chemistry, summa cum laude, in 1925.

Marriage
In his senior years Linus Pauling taught junior classes in "Chemistry for Home Economic Majors" . In one of these classes he met Ava Helen Miller, who he married on June 17, 1923; they had three sons (Crellin, Linus, Peter) and a daughter (Linda).

Early scientific career
Pauling later traveled to Europe on a Guggenheim Fellowship to study under German physicist Arnold Sommerfeld in Munich, Danish physicist Niels Bohr in Copenhagen, and Austrian physicist Erwin Schrödinger in Zürich. All three were experts working in the new field of quantum mechanics and other branches of physics. While he was studying at the Oregon Agricultural College, Pauling was first exposed to the idea of quantum theory and quantum mechanics. He became interested in seeing how it might help in the understanding of his chosen field of interest, the electronic structure of atoms and molecules. In Europe, Pauling was also exposed to one of the first quantum mechanical analyses of bonding in the hydrogen molecule, done by Walter Heitler and Fritz London. Pauling devoted the two years of his European trip to this work and decided to make this the focus of his future research. He became one of the first scientists in the field of quantum chemistry and a pioneer in the application of quantum theory to the structure of molecules. In 1927, he took a new position as an assistant professor at Caltech in theoretical chemistry.

Pauling began his faculty career at Caltech with a very productive five years, both continuing with his X-ray crystal studies and performing quantum mechanical calculations on atoms and molecules. He published approximately fifty papers in those five years and created five rules now known as Pauling's Rules. In 1929, he was promoted to associate professor, and in 1930, to full professor. By 1931, the American Chemical Society awarded Pauling the Langmuir Prize for the most significant work in pure science by a person 30 years of age or younger. In 1932, Pauling published what he regarded as his most important paper, in which he first laid out the concept of hybridization of atomic orbitals and analyzed the tetravalency of the carbon atom.

At Caltech, Pauling struck a close friendship with theoretical physicist Robert Oppenheimer, who was spending part of his research and teaching schedule away from Berkeley at Caltech every year. The two men planned to mount a joint attack on the nature of the chemical bond; apparently Oppenheimer would supply the mathematics and Pauling would interpret the results. However, this relationship soured when Pauling began to suspect that Oppenheimer was probably becoming too close to Pauling's wife, Ava Helen. Once, when Pauling was at work, Oppenheimer had come to their place and blurted out an invitation to Ava Helen to join him on a tryst to Mexico. Although she flatly refused, she reported this incident to Pauling. This, and her apparent nonchalance about the incident, disquieted him, and he immediately cut off his relationship with the Berkeley professor, leading to a coolness between them that would last their lives, although Oppenheimer did invite Pauling to be the head of the Chemistry Division of the atomic bomb project. (Pauling refused, saying that he was a pacifist).

In the summer of 1930, Pauling made another European trip, learning about the use of electrons in diffraction studies similar to the ones he had performed with X-rays. With a student of his, L. O. Brockway, he built an electron diffraction instrument at Caltech and used it to study the molecular structure of a large number of chemical substances.

Linus Pauling introduced the concept of electronegativity in 1932. Using the various properties of molecules, such as the energy required to break bonds and the dipole moments of molecules, he established a scale and an associated numerical value for most of the elements, the Pauling Electronegativity Scale, which is useful in predicting the nature of bonds between atoms in molecules.

Work on the nature of the chemical bond

Linus Pauling in 1954In the 1930s he began publishing papers on the nature of the chemical bond, leading to his famous textbook on the subject published in 1939. It is based primarily on his work in this area that he received the Nobel Prize in Chemistry in 1954 "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances". Pauling summarized his work on the chemical bond in The Nature of the Chemical Bond, one of the most influential chemistry books ever published. In the 30 years since its first edition was published in 1939, the book had been cited more than 16,000 times. Even today, many modern scientific papers and articles in important journals cite this work, more than half a century after first publication.

Part of Pauling's work on the nature of the chemical bond led to his introduction of the concept of orbital hybridization. While it is normal to think of the electrons in an atom as being described by orbitals of types such as s, p, etc., it turns out that in describing the bonding in molecules, it is better to construct functions that partake of some of the properties of each. Thus the one 2s and three 2p orbitals in a carbon atom can be combined to make four equivalent orbitals (called sp3 hybrid orbitals), which would be the appropriate orbitals to describe carbon compounds such as methane, or the 2s orbital may be combined with two of the 2p orbitals to make three equivalent orbitals (called sp2 hybrid orbitals), with the remaining 2p orbital unhybridized, which would be the appropriate orbitals to describe certain unsaturated carbon compounds such as ethylene. Other hybridization schemes are also found in other types of molecules.

Another area which he explored was the relationship between ionic bonding, where electrons are transferred between atoms, and covalent bonding where electrons are shared between atoms on an equal basis. Pauling showed that these were merely extremes, between which most actual cases of bonding fall. It was here especially that Pauling's electronegativity concept was particularly useful; the electronegativity difference between a pair of atoms will be the surest predictor of the degree of ionicity of the bond.

The third of the topics that Pauling attacked under the overall heading of "the nature of the chemical bond" was the accounting of the structure of aromatic hydrocarbons, particularly the prototype, benzene. The best description of benzene had been made by the German chemist Friedrich Kekulé. He had treated it as a rapid interconversion between two structures, each with alternating single and double bonds, but with the double bonds of one structure in the locations where the single bonds were in the other. Pauling showed that a proper description based on quantum mechanics was an intermediate structure containing some aspects of each. The structure was a superposition of structures rather than a rapid interconversion between them. The name "resonance" was later applied to this phenomenon. In a sense, this phenomenon resembles that of hybridization, described earlier, because it involves combining more than one electronic structure to achieve an intermediate result.

Work on structure of the atomic nucleus
On September 16, 1952, Linus Pauling opened a new research notebook with these words "I have decided to attack the problem of the structure of nuclei" (see his actual notes at Oregon State Special Collections). On October 15, 1965, Pauling published his Close-Packed Spheron Model of the atomic nucleus in two well respected journals, Science, and Proc. Natl. Acad. Sci.[2] For nearly three decades, until his death in 1994, Pauling published numerous papers on his spheron cluster model.

No modern text books on nuclear physics discuss the Pauling Spheron Model of the Atomic Nucleus, yet it provides a unique perspective, well published in the leading journals of science, on how fundamental "clusters of nucleons" can form shell structure in agreement with recognized theory of quantum mechanics. Pauling was well versed in quantum mechanics--he coauthored one of the first textbooks on the subject (Introduction to Quantum Mechanics with Applications to Chemistry by Linus Pauling, E. Bright Wilson, 1935). The Pauling spheron nucleon clusters include the deuteron[NP], helion [PNP], and triton [NPN].


Work on biological molecules

Double Helix
Discovery
William Astbury
Oswald Avery
Francis Crick
Erwin Chargaff
Max Delbrück
Jerry Donohue
Rosalind Franklin
Raymond Gosling
Phoebus Levene
Linus Pauling
Sir John Randall
Erwin Schrödinger
Alec Stokes
James Watson
Maurice Wilkins
Herbert Wilson
In the mid-1930s, Pauling decided to strike out into new areas of interest. Early in his career, he had mentioned a lack of interest in studying molecules of biological importance. But as Caltech was developing a new strength in biology, and Pauling interacted with such great biologists as Thomas Hunt Morgan, Theodosius Dobzhanski, Calvin Bridges, and Alfred Sturtevant, he started to become interested in studying biological molecules. His first work in this area involved the structure of hemoglobin. He was able to demonstrate that the hemoglobin molecule changes structure when it gains or loses an oxygen atom. As a result of this observation, he decided to make a more thorough study of protein structure in general. He returned to his earlier use of X-ray diffraction analysis. But protein structures were far less amenable to this technique than the crystalline minerals of his former work. The best X-ray pictures of proteins in the 1930s had been made by the British crystallographer William Astbury, but when Pauling tried, in 1937, to account for Astbury's observations quantum mechanically, he could not.

It took eleven years for Pauling to explain the problem: his mathematical analysis was correct, but Astbury's pictures were taken in such a way that the protein molecules were tilted from their expected positions. Pauling had formulated a model for the structure of hemoglobin in which atoms were arranged in a helical pattern, and applied this idea to proteins in general.

In 1951, based on the structures of amino acids and peptides and the planarity of the peptide bond, Pauling and colleagues correctly proposed the alpha helix and beta sheet as the primary structural motifs in protein secondary structure. This work exemplified his ability to think unconventionally; central to the structure was the unorthodox assumption that one turn of the helix may well contain a non-integral number of amino acid residues.

Pauling then suggested a helical structure for deoxyribonucleic acid (DNA) but in this structure he uncharacteristically made several basic mistakes, including making the phosphate group neutral, a fact which would no longer represent DNA as an acid[9]. Sir Lawrence Bragg had been disappointed that Pauling had won the race to find the alpha helix. Bragg's team had made a fundamental error in making their models of protein by not recognizing the planar nature of the peptide bond. When it was learned at the Cavendish Laboratory that Pauling was working on molecular models of the structure of DNA, Watson and Crick were allowed to make a molecular model of DNA using unpublished data from Maurice Wilkins and Rosalind Franklin at King's College. Early in 1953 James D. Watson and Francis Crick proposed a correct structure for the DNA double helix. One of the impediments facing Pauling in this work was that he did not have access to the high quality X-ray diffraction photographs of DNA taken by Rosalind Franklin, which Watson and Crick had seen. He planned to attend a conference in England, where he might have been shown the photos, but he could not do so because his passport was withheld at the time by the State Department, on suspicions that he had Communist sympathies. This was at the start of the McCarthy period in the United States.

Pauling also studied enzyme reactions and was among the first ones to point out that enzymes bring about reactions by stabilizing the transition state of the reaction, a view which is central to understanding their mechanism of action. He was also among the first scientists to postulate that the binding of antibodies to antigens would be due to a complementarity between their structures. Along the same lines, with the physicist turned biologist Max Delbruck, he wrote an early paper arguing that DNA replication was likely to be due to complementarity, rather than similarity, as suggested by a few researchers. This was made clear in the model of the structure of DNA that Watson and Crick discovered.

Molecular genetics
In November 1949 Linus Pauling, Harvey Itano, S. J. Singer and Ibert Wells published in the journal Science the first proof that a human disease was associated with a change in a specific protein. Using electrophoresis, they demonstrated that individuals with sickle cell disease had a modified hemoglobin in their red blood cells, and that individuals with the sickle cell trait, upon electrophoresis, had both the normal and abnormal hemoglobin. This was the first demonstration of a specific protein associated with a human disease, and the Mendelian inheritance of a change in that specific protein - the dawn of molecular genetics.

It was Vernon Ingram and J. A. Hunt in 1956 who determined that the change in the hemoglobin molecule in sickle cell disease and trait was the substitution of the glutamic acid in position 6 of the β-chain of the normal protein by valine.

Activism
Pauling had been practically apolitical until World War II, but the war changed his life profoundly, and he became a peace activist. During the beginning of the Manhattan Project, Robert Oppenheimer invited him to be in charge of the Chemistry division of the project, but he declined, saying that he was a pacifist. In 1946 he joined the Emergency Committee of Atomic Scientists, chaired by Albert Einstein, whose mission was to warn the public of the dangers associated with the development of nuclear weapons. His political activism prompted the U.S. State Department to deny him a passport in 1952, when he was invited to speak at a scientific conference in London. His passport was restored in 1954, shortly before the ceremony in Stockholm where he received his first Nobel Prize. Joining Einstein, Bertrand Russell and 8 other leading scientists and intellectuals he signed the Russell-Einstein Manifesto in 1955.

In 1957, Pauling began a petition drive in cooperation with biologist Barry Commoner, who had studied radioactive strontium-90 in the baby teeth of children across North America and concluded that above-ground nuclear testing posed public health risks in the form of radioactive fallout. He also participated in a public debate with the atomic physicist Edward Teller about the actual probability of fallout causing mutations. In 1958, Pauling and his wife presented the United Nations with a petition signed by more than 11,000 scientists calling for an end to nuclear-weapon testing. Public pressure subsequently led to a moratorium on above-ground nuclear weapons testing, followed by the Partial Test Ban Treaty, signed in 1963 by John F. Kennedy and Nikita Khrushchev. On the day that the treaty went into force, the Nobel Prize Committee awarded Pauling the Peace Prize, describing him as "Linus Carl Pauling, who ever since 1946 has campaigned ceaselessly, not only against nuclear weapons tests, not only against the spread of these armaments, not only against their very use, but against all warfare as a means of solving international conflicts." Interestingly, the Caltech Chemistry Department, wary of his political views, did not even formally congratulate him. However, the Biology Department did throw him a small party, showing they were more appreciative and sympathetic toward his work on radiation mutation.

Many of Pauling's critics, including scientists who appreciated the contributions that he had made in chemistry, disagreed with his political positions and saw him as a naïve spokesman for Soviet communism. He was ordered to appear before the Senate Internal Security Subcommittee, which termed him "the number one scientific name in virtually every major activity of the Communist peace offensive in this country." An extraordinary headline in Life magazine characterized his 1962 Nobel Prize as "A Weird Insult from Norway." Pauling was awarded the International Lenin Peace Prize by the USSR in 1970.

Work in the development of the electric car

Pauling contributed to the development of the first modern electric car - the Henney Kilowatt.In the late 1950s, Pauling became concerned with the problem of air pollution - particularly with the growing smog problem in Los Angeles. At the time, most scientists believed that the smog was due to chemical plants and refineries - not gasoline engine exhaust. Pauling worked with Arie Haagen-Smit and others at Caltech to show that smog was a product of automobile pollution instead of factory pollution. Shortly after this discovery, Pauling began work to develop a practical and affordable electric car. He joined forces with the engineers at the Eureka Williams company in the development of the Henney Kilowatt - the first speed-controlled electric car. After researching the electrophysics underlying the initial Kilowatt propulsion system, Pauling determined that traditional lead-acid batteries would not provide the power necessary to give electric cars the performance necessary to rival traditional gasoline powered cars. Pauling accurately predicted that the low top speed and the short range of the Henney Kilowatt would make them impractical and unpopular. Pauling insisted on making the car more practical before releasing it to the public, and recommended that the project be discontinued until the appropriate battery was available commercially. Unfortunately, Eureka Williams Company insisted that the production plans for the car proceed - leading to dismal sales and an additional delay in the development of practical electric cars.

Work in alternative medicine
In 1941, at age 40, Pauling was diagnosed with a serious form of Bright’s disease, a fatal renal disease. Experts believed then that Bright's disease was untreatable. With the help of Dr. Thomas Addis at Stanford, Pauling was able to control the disease with Addis' then unusual, low protein, salt-free diet. Addis also prescribed vitamins and minerals for all his patients.

In the late 1950s, Pauling worked on the role of enzymes in brain function, believing that mental illness may be partly caused by enzyme dysfunction. It wasn't until he read "Niacin Therapy in Psychiatry" by Abram Hoffer in 1965 that he realized that vitamins might have important biochemical effects unrelated to their prevention of associated deficiency diseases. Pauling published a brief paper, "Orthomolecular Psychiatry", in the journal Science in 1968 (PMID 5641253) that gave name and principle to the popular but controversial megavitamin therapy movement of the 1970s. Pauling coined the term "orthomolecular" to refer to the practice of varying the concentration of substances normally present in the body to prevent and treat disease.

Pauling's work on vitamin C in his later years generated controversy and was regarded by some adversaries in the field of medicine as outright quackery. [2] His ideas formed the basis of orthomolecular medicine, which is considered pseudoscience by some critics. The majority are often dismissive: "Scientific research has found no benefit from orthomolecular therapy for any disease."

He was first introduced to the concept of high-dose vitamin C by biochemist Irwin Stone in 1966 and began taking several grams every day to prevent colds. Excited by the results, he researched the clinical literature and published "Vitamin C and the Common Cold" in 1970. He began a long clinical collaboration with the British cancer surgeon, Ewan Cameron,  in 1971 on the use of intravenous and oral vitamin C as cancer therapy for terminal patients. Cameron and Pauling wrote many technical papers and a popular book, "Cancer and Vitamin C", that discussed their observations. After three disputed trials at the Mayo Clinic, Pauling, known for his blunt precision and candor, pointedly denounced Moertel's conclusions and handling of the final study as "fraud and deliberate misrepresentation", Pauling published critiques of the second Mayo-Moertel cancer trial's flaws over several years as he was able to slowly unearth some of the trial's undisclosed details. However, the wave of adverse publicity generated by Moertel and the media effectively undercut Pauling's credibility and his vitamin C work for a generation. Always precariously perched since his molecular biologically inspired crusade to stop atmospheric nuclear testing in the 1950s, the 1985 Mayo-Moertel confrontation left Pauling isolated from his institutional funding sources, academic support and a bemused public. He later collaborated with the Canadian physician, Abram Hoffer,  on a micronutrient regimen, including high-dose vitamin C, as adjunctive cancer therapy.

As of 2005, some physicians have called for a more careful reassessment of vitamin C, especially intravenous vitamin C, in cancer treatment. The selective toxicity of vitamin C for cancer cells has been demonstrated repeatedly. The Proceedings of the National Academy of Sciences recently published a paper demonstrating vitamin C killing cancer cells.

With two colleagues, Pauling founded the Institute of Orthomolecular Medicine in Menlo Park, California, in 1973, which was soon renamed the Linus Pauling Institute of Science and Medicine. Pauling directed research on vitamin C, but also continued his theoretical work in chemistry and physics until his death from prostate cancer in 1994. In his last years, he became especially interested in the possible role of vitamin C in preventing atherosclerosis and published three case reports on the use of lysine and vitamin C to relieve angina pectoris. In 1996, the Linus Pauling Institute moved from Palo Alto, California, to Corvallis, Oregon, to become part of Oregon State University, where it continues to conduct research on micronutrients, phytochemicals (chemicals from plants), and other constituents of the diet in preventing and treating disease.

Pauling's legacy
Pauling's contribution to science is held by many in the utmost regard. He was included in a list of the 20 greatest scientists of all time by the British magazine New Scientist, with Albert Einstein being the only other scientist from the twentieth century on the list. Gautam R. Desiraju, the author of the Millennium Essay in Nature (408: 407, 2000) claimed that Pauling was one of the greatest thinkers and visionaries of the millennium, along with Galileo, Newton, and Einstein (PMID 11100703). Pauling is also notable for the diversity of his interests: quantum mechanics, inorganic chemistry, organic chemistry, protein structure, molecular biology, and medicine. In all these fields, and especially on the boundaries between them, he made decisive contributions. His work on chemical bonding marks the beginning of modern quantum chemistry, and many of his contributions like hybridization and electronegativity have become part of standard chemistry textbooks. Although his valence bond approach fell short of accounting quantitatively for some of the characteristics of molecules, such as the paramagnetic nature of oxygen and the color of organometallic complexes, and would later be superseded by the Molecular Orbital Theory of Robert Mulliken, the strength of Pauling's theory has lain in its simplicity, and it has endured. Pauling's work on crystal structure contributed significantly to the prediction and elucidation of the structures of complex minerals and compounds. His discovery of the alpha helix and beta sheet is a fundamental foundation for the study of protein structure.

In his time, Pauling was frequently honored with the sobriquet "Father of molecular biology". His discovery of sickle cell anemia as a 'molecular disease' opened the way toward examining genetically acquired mutations at a molecular level.