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.
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."