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Oscar Davis Ratnoff (August 23, 1916 – May 20, 2008) was an American physician who conducted research on the process of
coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
and blood-related disorders. Ratnoff discovered the substance later known as
Factor XII Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme () of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the ''F12'' gene. Struct ...
and was one of the primary contributors to the delineation of the exact sequence that makes up the
clotting cascade Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
. He also made notable research contributions to the understanding of the
complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...
and to the detection and treatment of
hemophilia Haemophilia, or hemophilia (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, ...
. Ratnoff was a professor at the
Case Western Reserve University School of Medicine Case Western Reserve School of Medicine (CWRU SOM, CaseMed) is the medical school of Case Western Reserve University, a private research university in Cleveland, Ohio. It is the largest biomedical research center in Ohio. History On November 1 ...
, served as president of 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 ...
, and was elected to the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
. He remained active in research at Case Western Reserve until he was 85 and he died in
Cleveland Cleveland ( ), officially the City of Cleveland, is a city in the U.S. state of Ohio and the county seat of Cuyahoga County. Located in the northeastern part of the state, it is situated along the southern shore of Lake Erie, across the U.S. ...
a few years later.


Early life

Ratnoff was born prematurely, the son of a New York pediatrician. Ratnoff's father was an associate of notable pediatrician
Henry Koplik Henry Koplik (October 28, 1858 in New York City – April 30, 1927 in New York City) was an American physician. He was educated at the College of the City of New York and at the College of Physicians and Surgeons, and earned his medical degre ...
. Koplik advised Ratnoff's father that the newborn had little chance of survival and that he should allow the child to die. Instead, Ratnoff's father used hot water bottles to keep him warm. Ratnoff survived and became a strong student at the Brooklyn Boys' School before enrolling at
Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...
when he was 16. After graduating from Columbia, a 19-year-old Ratnoff entered the
Columbia University College of Physicians and Surgeons Columbia University Vagelos College of Physicians and Surgeons (VP&S) is the graduate medical school of Columbia University, located at the Columbia University Irving Medical Center in the Washington Heights neighborhood of Manhattan. Founded i ...
, where he graduated third in his medical school class. Ratnoff spent two years as an intern at
Johns Hopkins School of Medicine The Johns Hopkins University School of Medicine (JHUSOM) is the medical school of Johns Hopkins University, a private research university in Baltimore, Maryland. Founded in 1893, the School of Medicine shares a campus with the Johns Hopkins Hospi ...
and then was a research fellow with physiologist
Walter Cannon Walter Bradford Cannon (October 19, 1871 – October 1, 1945) was an American physiologist, professor and chairman of the Department of Physiology at Harvard Medical School. He coined the term "fight or flight response", and developed the theory ...
at
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 ...
. After another year spent working at hospitals in New York, Ratnoff enlisted in the military beginning in 1943. He was a member of the
United States Army Air Corps The United States Army Air Corps (USAAC) was the aerial warfare service component of the United States Army between 1926 and 1941. After World War I, as early aviation became an increasingly important part of modern warfare, a philosophical r ...
during
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
, teaching aviation physiology before working as a physician at an army hospital.


Career

Returning from the military in 1946, Ratnoff secured a fellowship at Johns Hopkins. He became an instructor in medicine there, leaving in 1950 to move to
Cleveland Cleveland ( ), officially the City of Cleveland, is a city in the U.S. state of Ohio and the county seat of Cuyahoga County. Located in the northeastern part of the state, it is situated along the southern shore of Lake Erie, across the U.S. ...
. Arthur Patek, the physician who recruited Ratnoff, may have also inspired some interest in coagulation. While a professor at Columbia, Patek had asked Ratnoff to review a research report on
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
from noted physician
Ernest Goodpasture Ernest William Goodpasture (October 17, 1886 – September 20, 1960) was an American pathologist and physician. Goodpasture advanced the scientific understanding of the pathogenesis of infectious diseases, parasitism, and a variety of ricketts ...
. Ratnoff became interested in the observation that the blood of such patients clotted after death but soon turned back to liquid. While practicing in Cleveland in 1954, Ratnoff treated a young railway worker John Hageman. The man had a long clotting time, but he had undergone successful surgery in the past without suffering from major bleeding. Working with biochemist
Earl Davie Earl Warren Davie (October 25, 1927 - June 6, 2020) was an American biochemist. He was a professor emeritus of biochemistry at the University of Washington. Davie studied the blood proteins involved in coagulation and was among the first scientist ...
, Ratnoff identified a protein missing in the man's blood. Ratnoff named the missing substance Hageman trait or Hageman factor. As other clotting factors had been discovered by the time of Ratnoff's encounter with his patient, Hageman factor became known as
factor XII Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme () of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the ''F12'' gene. Struct ...
. In 1964, Ratnoff and Davie published their model of the
clotting cascade Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
; a similar cascade was independently reported by
Robert Gwyn Macfarlane Robert Gwyn Macfarlane (26 June 1907 – 26 March 1987) was an English hematologist. Life Born in Worthing, Sussex, Gwyn Macfarlane left Cheltenham College in 1924 and a year later entered the Medical School of St Bartholomew's Hospital, L ...
of the
University of Oxford , mottoeng = The Lord is my light , established = , endowment = £6.1 billion (including colleges) (2019) , budget = £2.145 billion (2019–20) , chancellor ...
at around the same time. At Case Western University, Ratnoff was a professor, division chief of hematology-oncology and interim chief of medicine. Ratnoff had a long association with immunologist Irwin Lepow, and they conducted some of the early research on inhibition of the
complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...
. Ratnoff and Ted Zimmerman developed an
assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a ...
in the early 1970s to distinguish between classic hemophilia and
von Willebrand disease Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor ( ...
, then used the same technology to identify carriers of classic hemophilia. In 1972, 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 ...
selected Ratnoff to deliver its Henry M. Stratton Lecture. Three years later, Ratnoff served as the organization's president. In the 1980s, Ratnoff became concerned about the risk of HIV transmission to patients with hemophilia because these patients received
factor VIII Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the ''F8'' gene. Defects in this gene result in hemophilia A, a recessive X-linked coagulation disorder. ...
treatments created from pooled blood samples. He and his associates had been the first to identify some of the symptoms of HIV/AIDS in hemophilia patients. Noting that AIDS antibodies were being increasingly detected among hemophiliacs, Ratnoff proposed at a 1983
Centers for Disease Control The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
meeting that blood donors should be screened for
hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...
as a surrogate for HIV, as there was no good screening test for HIV at the time. Ratnoff also favored using
cryoprecipitate Cryoprecipitate, also called cryo for short, is a frozen blood product prepared from blood plasma. To create cryoprecipitate, fresh frozen plasma thawed to 1–6 °C is then centrifuged and the precipitate is collected. The precipitate is re ...
from local donors to treat these patients. Ultimately, his suggestions were not taken because of concerns that they would not result in enough clotting factor to meet patient demand. In the 1990s,
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including t ...
techniques allowed for the production of factor VIII without donated blood.


Honors and awards

Ratnoff was the second recipient of the H. P. Smith Award for Distinguished Pathology Educator from the
American Society for Clinical Pathology The American Society for Clinical Pathology (ASCP) is a professional association based in Chicago, Illinois Illinois ( ) is a state in the Midwestern United States. Its largest metropolitan areas include the Chicago metropolitan area, and ...
. He was elected to the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
in 1976 and received the organization's
Jessie Stevenson Kovalenko Medal The Jessie Stevenson Kovalenko Medal is awarded every two years by the US National Academy of Sciences "for important contributions to the medical sciences." It was first awarded in 1952 and involves a prize of $25,000 plus $50,000 for research. ...
in 1985. He was named a Master of the American College of Physicians in 1983. He received the ACP's John Phillips Memorial Award in 1974 for outstanding contributions to clinical medicine. He won the George M. Kober Medal from the
Association of American Physicians The Association of American Physicians (AAP) is an honorary medical society founded in 1885 by the Canadian physician Sir William Osler and six other distinguished physicians of his era for "the advancement of scientific and practical medicine." ...
in 1988.


Later life

Ratnoff, who received his first
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
(NIH) research grant in 1951, was still NIH-funded as an emeritus professor in the 1990s. He remained engaged in research at Case Western Reserve until 2001. He died in 2008 and was survived by Marian, his wife of 63 years, and by two children. A sister, Helen Ratnoff Plotz, preceded him in death. She compiled and edited anthologies of poetry.


References

{{DEFAULTSORT:Ratnoff, Oscar 1916 births 2008 deaths American hematologists Physicians from New York (state) Columbia University Vagelos College of Physicians and Surgeons alumni Johns Hopkins University faculty Case Western Reserve University faculty Members of the United States National Academy of Sciences Presidents of the American Society of Hematology