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
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."