Linus Pauling

• 1. Introduction

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  Linus Carl Pauling stands alone in the history of Nobel Prizes. He is the only person ever to have been awarded two unshared Nobel Prizes, one for Chemistry in 1954 and one for Peace in 1962. Scientific American named him one of the twenty greatest scientists of all time. And yet the man who unlocked the secret of the chemical bond, who first identified a disease caused by an abnormal protein, who helped push the world toward a nuclear test ban treaty, started life in a one-room apartment in Portland, Oregon, where his father worked as a traveling salesman for the Skidmore Drug Company.

  Herman Pauling died of a perforated ulcer on the 11th of June, 1910, leaving Linus, then nine years old, to grow up without him. The boy who would one day receive more than forty-seven honorary degrees left Washington High School in June without a diploma, denied the right to take two missing American history courses concurrently. The school awarded him an honorary diploma forty-five years later, after both Nobel Prizes had come in.

  What drove a boy from a modest Oregon family to become one of the founders of quantum chemistry and molecular biology? What made a celebrated scientist turn his energy toward nuclear disarmament, take on the US Senate, and sue a national magazine for a million dollars? And how did the same mind that cracked the structure of proteins miss the structure of DNA, calling it the biggest disappointment of his life? Those are the questions this documentary will answer.

• 2. A Chemist in the Making

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  Lloyd A. Jeffress, a childhood friend with a small chemistry lab kit, is the person Pauling credited with sparking his entire career. Pauling later described being "simply entranced by chemical phenomena, by the reactions in which substances, often with strikingly different properties, appear." That fascination drove him, as a high school student, to scavenge equipment from an abandoned steel plant and set up a basement laboratory called Palmon Laboratories with an older friend named Lloyd Simon.

  At fifteen, Pauling already had enough credits to enter Oregon Agricultural College, the institution now known as Oregon State University. To put himself through school, he worked part-time at a grocery store for eight dollars a week, then as an apprentice machinist at forty dollars a month, a salary soon raised to fifty. After his second year, he planned to drop out and support his mother, but the college offered him a paying position teaching quantitative analysis, a course he had just finished taking himself. He worked forty hours a week in the lab and classroom and earned a hundred dollars a month, enough to stay enrolled.

  It was in a chemistry course for home economics majors that he met Ava Helen Miller, the woman he would marry in 1923 and who would shape the second half of his life in ways he could not yet imagine. Engineering professor Samuel Graf had selected Pauling as his teaching assistant, a role that brought him into exactly that course. In 1922, Pauling graduated with a degree in chemical engineering and headed to the California Institute of Technology in Pasadena, where he received his PhD in physical chemistry and mathematical physics, summa cum laude, in 1925.

• 3. The Bond That Defined Chemistry

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  In 1926, a Guggenheim Fellowship sent Pauling to Europe to study under Arnold Sommerfeld in Munich, Niels Bohr in Copenhagen, and Erwin Schrödinger in Zürich. In Zürich he encountered one of the first quantum mechanical analyses of bonding in the hydrogen molecule, performed by Walter Heitler and Fritz London. He devoted the full two years of that trip to digesting this work and resolved to make it his life's research program.

  Back at Caltech, he published approximately fifty papers in his first five years on the faculty and created the five rules for predicting ionic crystal structures now known as Pauling's rules. In 1931 the American Chemical Society awarded him the Langmuir Prize for the most significant work in pure science by a person thirty years of age or younger. The following year he published what he considered his most important paper, introducing the concept of hybridization of atomic orbitals and analyzing the tetravalency of the carbon atom.

  Between 1937 and 1938 he delivered nineteen lectures at Cornell University as George Fischer Baker Non-Resident Lecturer in Chemistry. Those lectures became the bulk of his textbook The Nature of the Chemical Bond, first published in 1939. In the thirty years after that first edition, the book was cited more than sixteen thousand times. Chemistry historians have described it as "chemistry's most influential book of this century and its effective bible." It was primarily this body of work that the Nobel Committee recognized in 1954, citing his research into "the nature of the chemical bond and its application to the elucidation of the structure of complex substances."

  Pauling introduced the concept of electronegativity in 1932, establishing the Pauling Electronegativity Scale using the energy required to break bonds and the dipole moments of molecules. The scale gave chemists a reliable way to predict how bonds between different atoms would behave, and it remains in standard textbooks today alongside his concepts of hybridization and resonance.

• 4. Proteins, DNA, and a Missed Prize

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  In the mid-1930s, the biologically oriented funding priorities of the Rockefeller Foundation's Warren Weaver nudged Pauling toward molecules of life. His early work in this area included studies of hemoglobin with his student Charles D. Coryell; Pauling demonstrated that the hemoglobin molecule changes its structure when it gains or loses an oxygen molecule, a finding that set him on a longer investigation of protein structure in general.

  He ran into a wall with the best X-ray pictures of proteins available in the 1930s, made by the British crystallographer William Astbury. When Pauling tried in 1937 to account for Astbury's observations quantum mechanically, he could not. It took eleven years to discover why: Astbury had tilted the protein molecules from their expected positions during photography. Undistracted by that error, Pauling built a model in which atoms were arranged in a helical pattern.

  In 1951, Pauling, Robert Corey, and Herman Branson correctly proposed the alpha helix and the beta sheet as the primary structural motifs in protein secondary structure. Central to their model was the then-unorthodox assumption that one turn of the alpha helix contains a non-integer number of amino acid residues, specifically 3.7 per turn. Francis Crick would later acknowledge Pauling as the "father of molecular biology" for this and related work.

  DNA proved to be another matter. Pauling proposed that it was a triple helix, a model with several basic errors, including a proposal of neutral phosphate groups that conflicted with the well-known acidity of DNA. He later cited misleading density data and the lack of high-quality X-ray diffraction photographs as reasons for going wrong. Rosalind Franklin in England was producing the world's best images at the time, images that proved key to Watson and Crick's success. Pauling's assistant Robert Corey saw at least some of them at a summer 1952 conference in England. Pauling himself had been prevented from attending because the State Department withheld his passport on suspicion of Communist sympathies. Yet Pauling regained his passport within weeks and toured English laboratories well before writing his DNA paper; he had the opportunity to visit Franklin's lab and chose not to. Early in 1953, Watson and Crick proposed the correct double helix. Pauling called missing the structure of DNA the biggest disappointment of his life.

• 5. A Molecular Disease

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  In November 1949, Pauling published a paper in the journal Science with Harvey Itano, S. J. Singer, and Ibert Wells titled "Sickle Cell Anemia, a Molecular Disease." Using electrophoresis, the team demonstrated that individuals with sickle cell disease carry a modified form of hemoglobin in their red blood cells, while individuals with sickle cell trait carry both the normal and the abnormal forms.

  This was the first proof that a human disease could be caused by an abnormal protein. It was also the first demonstration that Mendelian inheritance determines the specific physical properties of proteins, not simply their presence or absence. Sickle cell anemia became, as a result, the first disease understood at the molecular level, and the paper is considered the dawn of molecular genetics.

  The sickle cell finding pushed Pauling to speculate that other diseases, including schizophrenia and other mental illnesses, might also result from flawed genetics. As chairman of the Division of Chemistry and Chemical Engineering at Caltech, he encouraged the hiring of researchers who took a chemical and biomedical approach to mental illness, a direction not always popular with established Caltech chemists. In 1951, he gave a lecture titled "Molecular Medicine." In the late 1950s he studied the role of enzymes in brain function. In the 1960s, working with his student Emile Zuckerkandl, he proposed the molecular evolutionary clock, the idea that mutations in proteins and DNA accumulate at a constant rate over time, a concept that remains central to modern evolutionary biology.

• 6. The Peace Activist

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  Robert Oppenheimer invited Pauling to head the Chemistry division of the Manhattan Project. Pauling declined, not wanting to uproot his family. He did, however, contribute to wartime research, serving as a principal investigator on fourteen OSRD contracts and designing the Pauling oxygen meter, manufactured by Arnold O. Beckman Inc. and later adapted for use in incubators for premature babies. In October 1948, President Harry S. Truman awarded Pauling the Presidential Medal for Merit.

  The aftermath of the Manhattan Project, and his wife Ava's deep pacifism, transformed him. In 1946, Pauling joined the Emergency Committee of Atomic Scientists, chaired by Albert Einstein, whose mission was to warn the public about the dangers of nuclear weapons. He signed the Russell-Einstein Manifesto on the 9th of July, 1955, alongside Bertrand Russell and eight other leading scientists and intellectuals.

  In May 1957, working with Washington University in St. Louis professor Barry Commoner, Pauling began circulating a petition among scientists to stop nuclear testing. On the 15th of January, 1958, he and Ava presented that petition to United Nations Secretary General Dag Hammarskjöld. It bore the signatures of 11,021 scientists representing fifty countries.

  Public pressure from scientists and the results of the Baby Tooth Survey, which demonstrated that above-ground nuclear testing spread radioactive strontium-90 through milk from cows that had eaten contaminated grass, helped push toward the Partial Test Ban Treaty. John F. Kennedy and Nikita Khrushchev signed it in 1963. On the 10th of October, 1963, the very day the treaty went into force, the Nobel Prize Committee awarded Pauling the Nobel Peace Prize for 1962, the year for which no prize had previously been given. The committee described him as someone 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." Pauling himself regretted that Ava was not awarded the prize alongside him.

• 7. Vitamin C and Controversy

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  In 1941, at age forty, Pauling was diagnosed with Bright's disease, a renal disease. Following the recommendations of his physician Thomas Addis, who recruited Ava Helen Pauling as "nutritionist, cook, and eventually as deputy 'doctor'," Pauling believed he controlled the disease through a low-protein, salt-free diet combined with vitamin supplements. That personal experience planted the seed for the most disputed chapter of his scientific life.

  Biochemist Irwin Stone introduced Pauling to the idea of high-dose vitamin C in 1966. Convinced of its value, Pauling began taking three grams every day to prevent colds. He published Vitamin C and the Common Cold in 1970 and began a long clinical collaboration with British cancer surgeon Ewan Cameron in 1971, studying intravenous and oral vitamin C as a possible therapy for terminal patients. He eventually published two studies of a group of one hundred allegedly terminal patients claiming that vitamin C increased survival by as much as four times compared to untreated patients.

  A re-evaluation in 1982 found that the vitamin C group had been less sick on entry to the study and had been judged terminal much earlier than the comparison group, making the groups not truly comparable. Later clinical trials at the Mayo Clinic, led by oncologist Dr. Edward T. Creagan, concluded that high-dose vitamin C at ten thousand milligrams was no better than placebo at treating cancer. Pauling denounced the Mayo Clinic findings as "fraud and deliberate misrepresentation," pointing out that the clinic used oral rather than intravenous vitamin C for most of the trial and treated patients for a median of only 2.5 months, whereas Pauling advocated continued high-dose supplementation for the rest of a patient's life.

  In 1973, Pauling founded what became the Linus Pauling Institute of Science and Medicine in Menlo Park, California, with Arthur B. Robinson and a third colleague. The institute moved in 1996 from Palo Alto to Corvallis, Oregon, where it became part of the Linus Pauling Science Center at Oregon State University. Pauling continued promoting vitamin C therapy, including a plan for treating heart disease with lysine and vitamin C, right up to his death from prostate cancer on the 19th of August, 1994, at his home in Big Sur, California. The Valley Library Special Collections at Oregon State University now hold his forty-six research notebooks.