Sickle Cell Anemia, a Molecular Disease

The paper, published in the November 25, 1949 issue of Science, reports a difference in electrophoretic mobility between hemoglobin from healthy individuals and those with sickle-cell anemia, with those with sickle cell trait having a mixture of the two types.

The paper helped establish that genes control not just the presence or absence of enzymes (as genetics had shown in the early 1940s) but also the specific structure of protein molecules.

[3] Linus Pauling was a prominent physical chemist at the California Institute of Technology (a main focal point of Warren Weaver's efforts to promote what he called "molecular biology" through Rockefeller Foundation grants).

In 1946, he set graduate student Harvey Itano (who had been previously trained as a physician) the task of finding differences in hemoglobin that might explain sickle cell disease.

In the 1960s, by which time it had been shown that sickle cell trait confers resistance to malaria and so the gene had both positive and negative effects and demonstrated heterozygote advantage, Pauling suggested that molecular diseases were actually the basis of evolutionary change.