Work from several scientists contributed to the discovery of Haemoglobin, the protein responsible for Sickle cell disease. In 1940 Irwin Sharman noticed a difference between the way light passed through sickled blood cells compared to normal cells. Dr. Castle, a Harvard professor in Medicine, understood the implication of this finding: a change in the spatial orientation inside these sickled blood cells. In a chance conversation Dr. Castle mentioned this to Linus Pauling, a scientist, who worked extensively on haemoglobin ultimately resulting in the identification of the two different forms of haemoglobin present in people with sickle cell.
Pauling tested the haemoglobin samples from normal individuals, Sickle cell patients and people with Sickle cell trait using a technique called electrophoresis, which separated proteins based on their size and electrical charge. While normal individuals had haemoglobin of one type distinguishable from the haemoglobin from patients with sickle cell, the individuals with the sickle cell trait had both. This was the first reported case where a change in protein structure was shown to be inherited in a Mendalian fashion.