ANCHE I GENI SBAGLIANO: LA TRIPLA ELICA DI PAULING

In February of 1953, “A proposed structure for the nucleic acids” was published in The Proceedings of the National Academy of Sciences. In this paper, which would turn out to be one of the most famous mistakes in 20th-century science, Linus Pauling and his collaborator on protein structures, Robert Corey, both at the California Institute of Technology, argued for a triple-helical structure for DNA. A few months later, James Watson and Francis Crick published the correct structure of DNA, a double helix, in Nature and later shared the Nobel Prize (1962) with Maurice Wilkins for this epochal discovery.

How did Pauling make such an error? He was the world’s pre-eminent chemist and x-ray crystallographer, a technique that he employed successfully for decades to elucidate the structure of hundreds of inorganic substances like mica and topaz and then used to crack the structure of huge protein molecules in a revolutionary series of stunning papers published in 1951. Even earlier, Pauling and Max Delbruck in 1940 introduced a mechanism for gene replication, and in a lecture in 1948 Pauling proposed that genes might consist of mutually complementary molecules. Pauling knew about Oswald Avery’s extraordinary work in 1944 that indicated that nucleic acids were capable of transmitting genetic information, but he still believed, as did many scientists, that the hereditary key was protein. While sailing to England in late 1947, Pauling met Erwin Chargaff, who told him about his observations of the ratios of subunits of nucleic acids to one another. This clue to DNA structure was not heeded by Pauling, who found Chargaff’s personality disagreeable.

The major piece of key evidence to which Pauling did not have access was the beautiful x-ray diffraction picture of the pure form of DNA that Rosalind Franklin and Wilkins had in England. Pauling himself had to make do with old pictures of a mixture of A and B forms of DNA, which didn’t correspond to any real structure. Pauling wrote to Wilkins and asked to see the better pictures, but his request was denied. He then wrote to Wilkins’s superior and was again rebuffed.

After WWII, Pauling, Einstein, Albert Schweitzer, Bertrand Russell, and a number of other concerned scientists and scholars began to warn about the potentially catastrophic consequences of nuclear war. Pauling was a staunch patriot and had contributed much to the war effort, including the development of an oxygen meter for use in submarines and aircraft, artificial blood substitutes, and new explosives, even one that became known as linusite! For these efforts, he was awarded the Presidential Medal for Merit by President Truman and a certificate of appreciation from the War Department. But just a few years later, opposition to atomic bombs and their testing in the atmosphere was increasingly viewed by many as unpatriotic and even subversive.
A symposium to discuss Pauling’s protein structures was scheduled by the Royal Society in England for May 1952, at which time Franklin’s pictures of DNA would be available. When Pauling tried to renew his passport to attend, his application was denied on the grounds that his international travel “would not be in the best interests of the United States”. During this period of intense anti-Communism, some in the State Department were suspicious of Pauling’s political positions. Ironically, he was also being attacked by the Soviet government, which believed his chemical concepts to be incompatible with Marxism. Pauling’s passport application was eventually approved, although too late for the symposium. He visited England in the summer of 1952 but did not ask to see Franklin’s data. He may have been inhibited in doing so, having already been refused twice.

Pauling’s political activism also interfered with approval of his grant applications for research submitted to the Public Health Service. Passport problems surfaced yet again after Pauling won the Nobel Prize in Chemistry in 1954 and threatened to prevent him from accepting the award in Stockholm. And finally, a deep rift opened between Pauling and Caltech’s administrators that led to his departurefrom Caltech in 1963 just after winning the Nobel Peace Prize, an award that largely vindicated Pauling. Today, of course, few people would support the atmospheric testing of nuclear weapons.

Some have opined that Pauling was hurried, overconfident, or didn’t work hard enough on the structure of DNA, whereas Watson and Crick were extremely focused and intensely conscious of the “race” to discover the structure. Indeed, Pauling was working on many scientific problems during this period, as well as working for peace, and he did not pursue the structure of DNA to the exclusion of other scientific problems and social issues. In the late 1940s and early 1950s, he published papers on the serological properties of simple substances, antigen-antibody reactions, valence-bond theory, biological specificity, bonds in metallic compounds, the cause of sickle-cell anemia, the structure of hemoglobin, the alpha helix and pleated-sheet structures of proteins, the crystal structure of inorganic compounds, and a theory of ferromagnetism. He also prepared his famous textbook, College Chemistry, as well as the first and second editions of his classic textbook, General Chemistry. Francis Crick has written that this book provided almost his only education in organic chemistry. Indeed, when Pauling and Corey proposed the triple helix, Crick consulted General Chemistry and confirmed that Pauling had made a chemical error and had the wrong structure. When Pauling saw the Watson and Crick model of DNA, he immediately recognized it as the correct structure and graciously praised them for the discovery.

Francis Crick credits Pauling as the major founder of the science of molecular biology for his work on molecular complementariness, biological specificity, and the weak forces that govern many biological interactions. According to Nobel Laureate Arthur Kornberg, Pauling deserved a Nobel Prize in Medicine for his discovery of the molecular cause of sickle-cell anemia and his work on protein structure. Had it not been for the political persecution by the government, it is quite possible that Pauling would have quickly deduced the double helix had he been able to see Franklin’s data in England and may have won yet another Nobel Prize.

For more information on this topic, please visit the Ava Helen and Linus Pauling Papers website, where “Linus Pauling and the Race for DNA: A Documentary History” is posted. Force of Nature: The Life of Linus Pauling by Tom Hager also provides illuminating details.