William B. Castle (hematologist)
Encyclopedia
William Bosworth Castle was an eminent American physician
and physiologist who transformed hematology
from a "descriptive art to a dynamic interdisciplinary science."
, 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.
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 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 Caltech 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
.
. 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.
.
, 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.
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
and physiologist who transformed hematology
Hematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
from a "descriptive art to a dynamic interdisciplinary science."
Work
William B. Castle discovered gastric intrinsic factorIntrinsic factor
Intrinsic factor also known as gastric intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the small intestine...
, the absence of which causes pernicious anemia
Pernicious anemia
Pernicious anemia is one of many types of the larger family of megaloblastic anemias...
. 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
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
(cobalamin) and provides an effective therapy for pernicious anemia.
Castle then showed that tropical sprue
Tropical sprue
Tropical sprue is a malabsorption disease commonly found in the tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine.It differs significantly from coeliac sprue.-Symptoms and signs:...
was caused by intestinal impermeability to this and other hematopoietic factors in food. In closely related studies Castle defined the need for iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
for the bone marrow to make hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
. Without adequate iron in the diet, children and adults develop iron deficiency anemia
Iron deficiency anemia
Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...
, a common scourge.
Castle and his team later characterized the red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
defects that are responsible for paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria , sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterised by complement-induced intravascular hemolytic anemia , red urine and thrombosis...
and hereditary spherocytosis
Hereditary spherocytosis
Hereditary spherocytosis is a genetically-transmitted form of spherocytosis, an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped , and therefore more prone to hemolysis.-Symptoms:As in non-hereditary spherocytosis,...
. They also did important research on sickle cell disease.
A train ride
In 1945 Castle and the biochemist Linus PaulingLinus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
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
Birefringence
Birefringence, or double refraction, is the decomposition of a ray of light into two rays when it passes through certain anisotropic materials, such as crystals of calcite or boron nitride. The effect was first described by the Danish scientist Rasmus Bartholin in 1669, who saw it in calcite...
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 Caltech 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
Molecular medicine
Molecular medicine is a broad field, where physical, chemical, biological and medical techniques are used to describe molecular structures and mechanisms, identify fundamental molecular and genetic errors of disease, and to develop molecular interventions to correct them...
.
Life
Castle was born and educated in Cambridge, MassachusettsCambridge, Massachusetts
Cambridge is a city in Middlesex County, Massachusetts, United States, in the Greater Boston area. It was named in honor of the University of Cambridge in England, an important center of the Puritan theology embraced by the town's founders. Cambridge is home to two of the world's most prominent...
. He entered Harvard College
Harvard College
Harvard College, in Cambridge, Massachusetts, is one of two schools within Harvard University granting undergraduate degrees...
there in 1914 and at the end of his third year of college enrolled in Harvard Medical School
Harvard Medical School
Harvard Medical School is the graduate medical school of Harvard University. It is located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts....
. Upon graduating from medical school he did a medical internship at the Massachusetts General Hospital
Massachusetts General Hospital
Massachusetts General Hospital is a teaching hospital and biomedical research facility in the West End neighborhood of Boston, Massachusetts...
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
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
.) In 1923 Castle accepted a position in the laboratory of Cecil Drinker at the Harvard School of Public Health
Harvard School of Public Health
The Harvard School of Public Health is one of the professional graduate schools of Harvard University, located in the Longwood Area of the Boston, Massachusetts neighborhood of Mission Hill, which is next to Harvard Medical School. HSPH is considered a significant school focusing on health in the...
. In 1925 Castle went back into a clinical setting at the Thorndike Memorial Laboratory on the Harvard service at the Boston City Hospital
Boston City Hospital
The Boston City Hospital in Boston, Massachusetts, 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
American Academy of Arts and Sciences
The American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
in 1931.
Teaching
Aside from his work in research, Castle was a highly influential teacher. He had "three generations of trainees"http://www.nap.edu/readingroom/books/biomems/wcastle.html -- his intellectual children, grandchildren and great-grandchildren—who put his stamp of excellence upon the field of hematologyHematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
.
Family
William B. Castle was the son of William E. CastleWilliam E. Castle
William Ernest Castle was an early American geneticist.-Early years:William Ernest Castle was born on a farm in Ohio and took an early interest in natural history...
, professor of zoology at Harvard, a pioneer in mammalian genetics and a member of the U.S. National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
. 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 SciencesUnited States National Academy of SciencesThe National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
- Oral History of William Bosworth Castle from the American Society of HematologyAmerican Society of HematologyThe American Society of Hematology is a professional organization representing hematologists. It was founded in 1958. Its annual meeting is held in December of every year and has attracted nearly 20,000 attendees. The society publishes the medical journal Blood, one of the most cited peer-review...
External links
- Key Participants: William B. Castle - It's in the Blood! A Documentary History of Linus Pauling, Hemoglobin, and Sickle Cell Anemia