William B. Castle (hematologist)

William Bosworth Castle (1897-1990) was an eminent American physician and physiologist who transformed hematology from a "descriptive art to a dynamic interdisciplinary science."

Work
William B. Castle discovered gastric intrinsic factor, the absence of which causes pernicious anemia. His team extracted the active principle of gastric intrinsic factor from liver. It proved to be vitamin B12 (cobalamin) and provided an effective therapy for pernicious anemia.

Castle then showed that tropical sprue was caused by intestinal impermeability to this and other hematopoietic factors in food. In closely related studies Castle defined the need for iron for the bone marrow to make hemoglobin. Without adequate iron in the diet, children and adults develop iron deficiency anemia, a common scourge.

Castle and his team later characterized the red blood cell defects that are responsible for paroxysmal nocturnal hemoglobinuria and hereditary spherocytosis. They also did important research on sickle cell disease.

A train ride
In 1945 Castle and the biochemist Linus Pauling traveled together by overnight train from Denver to Chicago. On the train Castle told Pauling about some of the work he had been doing on sickle cell disease and mentionned that when red cells sickled they changed shape and showed birefringence in polarized light. Castle said that some kind of molecular alignment or orientation must be occurring.

Castle ventured to suggest that this might be "the kind of thing" in which Pauling might be interested. It was. The following year, Pauling and his colleagues at Cal Tech started their studies that proved the hemoglobin in sickle cell disease was abnormal. This discovery of what Pauling came to call a "molecular disease" was revolutionary. Thanks to Castle's suggestion to Pauling, we entered the present era of molecular medicine. 

Life
Castle was born and educated in Cambridge, Massachusetts. He entered Harvard College there in 1914 and at the end of his third year of college enrolled in Harvard Medical School. Upon graduating from medical school he did a medical internship at the Massachusetts General Hospital from 1921-1923. At the Mass General he had his first direct exposure to some of the great clinicians of the time, including Chester M. Jones, with whom he collaborated on his first medical publication, and George R. Minot who later became Castle's mentor and unflagging supporter. (Minot later shared the Nobel Prize.) In 1923 Castle accepted a position in the laboratory of Cecil Drinker at the Harvard School of Public Health. In 1925 Castle went back into a clinical setting at the Thorndike Memorial Laboratory on the Harvard service at the Boston City Hospital. He remained on the faculty of Harvard Medical School for his entire long career.

Teaching
Aside from his work in research, Castle was a highly influential teacher. He had "three generations of trainees" -- his intellectual children, grandchildren and great-grandchildren -- who put his stamp of excellence upon the field of hematology.

Family
William B. Castle was the son of William E. Castle, professor of zoology at Harvard, a pioneer in mammalian genetics and a member of the US National Academy of Sciences. In 1939, when William B. Castle was also elected to the Academy, the two Castles became the first father and son members in the history of that prestigious body. William B. Castle married Louise Muller in 1933 and they had a daughter and son and, reportedly, a very good marriage.

Source

 * Biographical Memoir of William B. Castle by James H. Jandl for the National Academy of Sciences