WILLIAM B. CASTLE

October 21, 1897–August 9, 1990

BY JAMES H. JANDL

WILLIAM BOSWORTH CASTLE died peacefully on August 9, 1990, at age ninety-two. Castle's eminence in medicine and physiology was secured early in his career by the celebrated discovery of gastric intrinsic factor, absence of which is the proximal cause of pernicious anemia. Within a very short period, he and his colleagues extracted the active hematopoietic principle of liver, characterized it as a B vitamin, later identified as vitamin B12 (cobalamin), and formulated an effective parenteral therapy for pernicious anemia. He then demonstrated that tropical sprue was caused by “intestinal impermeability” to this and other hematopoietic factors present in food and in related studies defined the stoichiometric need for iron in hemoglobin synthesis. This body of work transported hematology from a descriptive art to a dynamic interdisciplinary science. In ensuing years Castle and associates characterized the red cell defects responsible for paroxysmal nocturnal hemoglobinuria and hereditary spherocytosis and established the role of heightened hemoglobin viscosity in the pathogenesis of sickle cell anemia.

Castle once attributed his record of achievements to “being in the right place at the right time—especially with the



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