Clinical States Associated with Alterat of the Hemoglobin Molecule

Abstract

The role played by Dr. William B. Castle, the first Minot lecturer, in stimulating the initial studies of hemoglobin in sickle-cell anemia is not generally known. It was his description, in 1945, of the effect of oxygen and carbon dioxide on sickling, in Dr. Linus Pauling's presence, which prompted Dr. Pauling to postulate that an abnormal hemoglobin was present in the sickling cells.¹ The following year, Dr. Pauling suggested that I begin the investigation which culminated in the detection of an inherited abnormal hemoglobin in sickle-cell anemia and sickle-cell trait.² By 1951 two more abnormal hemoglobins (Figs. 1-5) were found to be associated with sicklecell disease.* By 1953, ten distinct hereditary clinical states were known to be associated with abnormal hemoglobin metabolism.⁵ During the past year five more abnormal hemoglobins have been found,† two in clinical states resembling Cooley's anemia ‡ and two in asymptomatic states.§ While part of what