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William Bosworth Castle (October 21, 1897 – August 9, 1990) was an American
physician A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...
and physiologist who transformed hematology from a "descriptive art to a dynamic interdisciplinary science."


Life

Castle was born to William E. Castle and his wife in
Cambridge, Massachusetts Cambridge ( ) is a city in Middlesex County, Massachusetts, United States. As part of the Boston metropolitan area, the cities population of the 2020 U.S. census was 118,403, making it the fourth most populous city in the state, behind Boston ...
. His father was a professor of zoology at Harvard, a pioneer in mammalian genetics, and a member of the U.S. National Academy of Sciences. The young Castle was educated in local schools and entered
Harvard College Harvard College is the undergraduate college of Harvard University, an Ivy League research university in Cambridge, Massachusetts. Founded in 1636, Harvard College is the original school of Harvard University, the oldest institution of higher lea ...
in 1914. At the end of his third year of college, he enrolled in
Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
. 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 The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
.) In 1923 Castle accepted a position in the laboratory of Cecil Drinker at the
Harvard School of Public Health The Harvard T.H. Chan School of Public Health is the public health school of Harvard University, located in the Longwood Medical Area of Boston, Massachusetts. The school grew out of the Harvard- MIT School for Health Officers, the nation's firs ...
. In 1925 Castle went back into a clinical setting at the Thorndike Memorial Laboratory on the Harvard service at the
Boston City Hospital The Boston City Hospital (1864–1996), in Boston, Massachusetts, was a public hospital, located in the South End. It was "intended for the use and comfort of poor patients, to whom medical care will be provided at the expense of the city, and . ...
. 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 The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, a ...
in 1931. In 1939, Castle was elected to the National Academy of Sciences. The two Castles became the first father-and-son members in the history of that prestigious body.


Marriage and family

William B. Castle married Louise Muller in 1933. They had a daughter Anne and a son William.


Work

William B. Castle discovered gastric
intrinsic factor Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption ...
, the absence of which causes
pernicious anemia Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...
. 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 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
(cobalamin) and provides an effective therapy for pernicious anemia. In 1931 Castle went to
Puerto Rico Puerto Rico (; abbreviated PR; tnq, Boriken, ''Borinquen''), officially the Commonwealth of Puerto Rico ( es, link=yes, Estado Libre Asociado de Puerto Rico, lit=Free Associated State of Puerto Rico), is a Caribbean island and unincorporated ...
sponsored by the Rockefeller Foundation
International Health Board The Rockefeller Foundation is an American private foundation and philanthropic medical research and arts funding organization based at 420 Fifth Avenue, New York City. The second-oldest major philanthropic institution in America, after the Car ...
in a public health project. He conducted a several-month study for the Rockefeller Anemia Commission, as part of the Rockefeller Foundation's work in trying to combat hookworm in the Caribbean. Anemia was widespread on the island because of the endemic parasite hookworm and
tropical sprue Tropical sprue is a malabsorption disease commonly found in tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine. It differs significantly from coeliac sprue. It appears to be a more ...
, the latter a disease which scientists thought possibly related to diet. Castle was assisted by
Cornelius P. Rhoads Cornelius Packard "Dusty" Rhoads (June 9, 1898 – August 13, 1959) was an American pathologist, oncologist, and hospital administrator who was involved in a racist scandal and subsequent whitewashing in the 1930s. Beginning in 1940, he served a ...
, known as Dusty, who was affiliated with the Rockefeller Institute in New York and later became head of Memorial Hospital for Cancer Care and Research. They showed that
tropical sprue Tropical sprue is a malabsorption disease commonly found in tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine. It differs significantly from coeliac sprue. It appears to be a more ...
was caused by intestinal impermeability to this and other hematopoietic factors in food. They were able to use liver extract therapy to treat tropical sprue successfully. It is still a problem in Puerto Rico, but it can be treated with folic acid and a 3-6 month course of antibiotics. In closely related studies, Castle defined the need for
iron Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...
for the bone marrow to make
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
. Without adequate iron in the diet, children and adults develop
iron deficiency anemia Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, s ...
, a common scourge. Castle and his team later characterized the
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
defects that are responsible for
paroxysmal nocturnal hemoglobinuria Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occu ...
and
hereditary spherocytosis Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (s ...
. They also did important research on
sickle cell disease Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red b ...
. It is a genetic disease found at high frequency among people of African ethnicity.


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.


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 suggested 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 The California Institute of Technology (branded as Caltech or CIT)The university itself only spells its short form as "Caltech"; the institution considers other spellings such a"Cal Tech" and "CalTech" incorrect. The institute is also occasional ...
began the studies that eventually showed that the hemoglobin in sickle cell disease was abnormal. Pauling and coworkers wrote Sickle Cell Anemia, a Molecular Disease.


References


Sources


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 The American Society of Hematology (ASH) is a professional organization representing hematologists. It was founded in 1958. Its annual meeting is held in December of every year and has attracted more than 30,000 attendees. The society publishes t ...
*


External links


Key Participants: William B. Castle
- ''It's in the Blood! A Documentary History of Linus Pauling, Hemoglobin, and Sickle Cell Anemia'', Oregon State University
"William Bosworth Castle"
National Academy of Sciences Biographical Memoir
William B. Castle Papers, 1889-1991 (inclusive),1925-1989 (bulk). H MS c174. Harvard Medical Library, Francis A. Countway Library of Medicine, Boston, Mass.
{{DEFAULTSORT:Castle, William Bosworth 1897 births 1990 deaths American geneticists American physiologists Fellows of the American Academy of Arts and Sciences Harvard Medical School alumni Harvard Medical School faculty Harvard University staff People from Cambridge, Massachusetts Harvard College alumni American tropical physicians