It's in the Blood! A Documentary History of Linus Pauling, Hemoglobin and Sickle Cell Anemia Narrative  
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Theoretical Conclusions
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The article also suggested a theory describing the sickling process, which came purely from Pauling. He stated many times that his work in immunology incited his immediate understanding of the sickling process when Castle mentioned it. Indeed, Pauling proposed a similar mechanism for the sickling process as he had presented in 1940 to explain his theory about the formation of antibodies. Specifically, Pauling assumed that the globins differed from one another near where the iron attached, and that the sickling happened because a region in the globin of sickle cell anemia hemoglobin had a different surface area than normal hemoglobin. In the absence of oxygen, the two complementary regions of sickle cell hemoglobin molecules bind together forming long chains and therefore hinder blood flow in the body. In comparison, the presence of oxygen obstructs the two complementary regions from binding and the various red blood cells do not aggregate.

Moreover, their experiments proved Pauling's theory that the abnormal structure of sickle cell hemoglobin causes the disease, sickle cell anemia. Their term "molecular disease" brought attention to the structural change at the molecular level. By linking a structural abnormality of a substance inside the human body to a disease, Pauling and his colleagues demonstrated that genes determine the structure of proteins, and that abnormal protein structure can cause a disease.

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Audio Clip  Audio: Drawing the Analogy between Antibodies and the Sickle Cell Anemia Process. February 26, 1962. (0:57) Transcript and More Information

Video Clip  Video: William Castle's Thoughts on Sickle Cell Anemia. May 20, 1986. (2:05) Transcript and More Information

See Also: Letter from William Castle to Linus Pauling. September 28, 1955. 

Click images to enlarge 

Pastel drawing of Hemoglobin at 100 angstroms, 1964.

Pastel drawing of Hemoglobin at 20 angstroms, 1964.

"It appears, therefore, that while some of the details of this picture of the sickling process are as yet conjectural, the proposed mechanism is consistent with experimental observations at hand and offers a chemical and physical basis for many of them. Furthermore, if it is correct, it supplies a direct link between the existence of “defective” hemoglobin molecules and the pathological consequences of sickle cell disease."

Linus Pauling
April 1949
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