William Bosworth Castle

William Bosworth Castle (October 21, 1897 – August 9, 1990) was an 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. Intrinsic factor was necessary to facilitate the absorption of an 'extrinsic factor' from the diet. Whipple, Minot and Murphy were awarded the Nobel Prize for Physiology and Medicine, in 1934, for the discovery of the "anti-pernicious anæmia factor" from their experiments with liver in the diet. The 'extrinsic factor' is now known as vitamin B12 (cobalamin) and provides 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 mentioned that when red cells sickled, they changed shape and showed birefringence in polarized light. Castle believed 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 Caltech began the studies that eventually showed that the hemoglobin in sickle cell disease was abnormal. This discovery of what Pauling came to call a "molecular disease" was revolutionary.

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 career. He was elected a Fellow of the American Academy of Arts and Sciences in 1931.

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 U.S. 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 (Anne) and a son (William) and, reportedly, a very good marriage.

Source

 * Biographical Memoir of William B. Castle by James H. Jandl for the National Academy of Sciences
 * Oral History of William Bosworth Castle from the American Society of Hematology