Thinking Between Disciplines: Immunological Interests and Beyond

I believe that chemistry will play a very important part in the golden age of biology that is now beginning.”
– Linus Pauling, “Molecular Structure and Biological Specificity,” July 17, 1947.

One of the reasons why Linus Pauling enjoyed such a prolific and diverse scientific career was his ability to combine and draw inspiration from rather disparate interests and research questions.

Indeed, structural chemistry – the discipline with which Pauling is most commonly associated – appealed to Pauling in part because it allowed him to consider the physical causes underlying the chemical nature of certain biological phenomena in concert with known principles of chemical interaction.  In other words, Pauling viewed structural chemistry as the avenue by which he could best utilize the tools not only of chemistry, but of physics and biology as well.

Many of Pauling’s laboratory experiments rested on knowledge and methods borrowed liberally from biology, medicine, chemistry and physics. In a 1946 proposal for a program of fundamental research in biology and medicine at Caltech, Pauling emphasized that the long-established cooperation of the Institute’s divisions of Biology, Chemistry, and Chemical Engineering were resulting in a vigorous and successful “attack” on the “great fundamental problems of biology and medicine.” As he sought to justify the expansion of these interacting programs, Pauling wrote that the “primary features” of their organization were “the presence of a group of men rigorously trained in the exact sciences and interested in attacking…broad problems.”

Of nearly-equal importance was an “unusual spirit of cooperation.” Such ‘unusual cooperation,’ in Pauling’s opinion, could be expected to produce work that was at once “sound but imaginative,” and indebted to “the transfer of ideas among different fields…ranging from quantum mechanics to animal physiology.” Pauling’s ideas on the nature of hemoglobin and sickle cell anemia were two of the ‘sound but imaginative’ ideas that arose out of the broader culture of interdisciplinary laboratory research.

In the 1930s Pauling came under the influence of a prominent immunologist, Karl Landsteiner, who helped to turn his attention and interest towards the mechanism of immunological response. To Pauling, the fundamentals of immune response in the body seemed reminiscent of the folding of hemoglobin in the presence of iron. Both mechanisms underscored the importance of the physical structure of a molecule in influencing its chemical interactions.

Pauling’s work on both the nature of hemoglobin as well as the immunological reaction to antigens and foreign proteins were linked practically, as well as conceptually, to his hemoglobin research. As he came to learn more about immune response, Pauling applied some of this knowledge to increasing the practical value of his work on the development of Oxypolygelatin, a blood substitute created as part of the Pauling’s contributions to the Allied effort during World War II.

An original container of 5% Oxypolygelatin in normal saline. Developed by Linus Pauling as part of his scientific war work research program, mid-1940s.

An original container of 5% Oxypolygelatin in normal saline. Developed by Linus Pauling as part of his scientific war work research program, mid-1940s.

This project, which was not completed to fruition until 1949, was vexed by certain problems having much to do with the nature of blood in the human body. In a handwritten note from 1945, Pauling suggested that foremost among his concerns vis-a-vis the creation of a suitable blood alternative were both a “lack of toxicity,” and a lack of “antigenicity.”

Pauling’s ideas on the nature of hemoglobin, sickle cell anemia and the blood substitute Oxypolygelatin were all born of his ability to fruitfully-combine the methods of several different disciplines with the expertise of his colleagues and fellow researchers. Even moreso, this remarkable body of work constitutes a clear example of the important place that interdisciplinarity can assume in scientific research.

To learn more about Pauling’s research on hemoglobin, immunology and Oxypolygelatin, please visit the website It’s in the Blood!  A Documentary History of Linus Pauling, Hemoglobin and Sickle Cell Anemia.

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