Oscar Davis Ratnoff
Authors: C. Richmond
Journal: BMJ (2008)

Oscar Ratnoff discovered the Hageman and Fitzgerald clotting factors, now known as factor XII and high molecular weight kininogen. Long before genetic tests were available, he devised a method for detecting carriers of haemophilia. He co-discovered the sequence of chemical events in clotting, which he termed the waterfall hypothesis to distinguish it from the rival—but compatible—cascade hypothesis.

In the early 1980s he realised that the AIDS epidemic among haemophiliac patients could be due to them receiving factor VIII from pooled donations, which he realised conformed to Koch’s postulates and could spread contamination from a single donor. He had seen the incidence of AIDS antibodies in haemophiliac patients rise from 15% in 1980 to 64% in 1984, and at a 1983 meeting of the Centers for Disease Control (CDC) he argued for screening donors for hepatitis B as a surrogate for AIDS. He also argued against using factor VIII concentrates in favour of cryoprecipitate from local, known donors. His objections were dismissed because of the need to produce enough factor VIII for the marketplace.

Little was known about clotting at the start of his career. It was known that prothrombin was converted to thrombin by thrombokinase, and it was thought that this converted fibrinogen to fibrin, though some were aware that other plasma factors were needed, and haemophiliac patients were deemed to be short of “antihaemophilic factor.”

Oscar Ratnoff was a premature baby, and his paediatrician father was advised by a colleague, Dr Henry Koplik (of the eponymous spots), that Oscar had a dismal prognosis and he should “let the child go.” His parents ignored the advice and kept him warm with hot water bottles. At Brooklyn Boys’ School he was known as Professor Oscar, the boy chemist.

He entered Columbia University at the age of 16 and Columbia College of Physicians and Surgeons at the age of 19. He graduated third in his class but was refused an internship at Columbia Presbyterian Hospital as it had filled its Jewish quota. He went instead to the Johns Hopkins Hospital in Baltimore for two years, developing atypical pneumonia while there and surviving the fresh winter air treatment, which gave him thrombophlebitis and a pulmonary embolism. He went on to Harvard as the last but one research fellow to the great physiologist Walter Cannon, who unravelled the physiology of the “fight, flight, or fright” response. He then returned to New York, to the Goldwater and then the Montefiore Hospitals, for a further year.

In 1943 he enlisted for three years. When he was demobbed he was offered a training fellowship at Johns Hopkins, where he spent four years, rising to instructor in medicine. In 1950 he moved to Cleveland, where he spent the rest of his career, starting as assistant professor of medicine at Case Western University and ending as professor and director of the department of medicine.

He was invited there by a teacher from his medical school, Arthur Patek, who several years earlier had asked Oscar to investigate a report on cirrhosis of the liver. Oscar noted a report by Dr Ernest Goodpasture (of the eponymous syndrome) that blood from cirrhotic patients clots normally but reliquefies within hours. This problem, and the questions it generated, became his life’s work.

Shortly after his arrival at Cleveland Oscar saw John Hageman, a 17 year old railwayman who had a remarkably long clotting time but no symptoms of haemorrhage, despite dental extraction and tonsillectomy. The clotting time could be restored by adding plasma from patients with any of the other known clotting factor deficiencies. Oscar then discovered another family with the trait, which he showed was inherited as a Mendelian recessive. He named the factor after the index patient because he regarded patients as the most important people in medicine, and John Hageman, a cheerful, jolly man, was delighted with his medical fame. Oscar showed that the factor existed as a precursor that could be active by contact with glass, collagen, and several other materials. At the time of his discovery, some other factors, including Von Willebrand factor and factors V, VII, VIII, IX, and XI, had been discovered and the rest followed shortly after, but their sequence and interactions remained a mystery until he and others unravelled them.

In a long and productive career he published over 400 papers—the last in 2001—and was the Journal of Clinical Investigation’s most prolific contributor. He was made emeritus professor in 1987 but continued working until he was 85. He never took the examinations that would qualify him as a haematologist but became president of the American Society of Hematology. He received many honours and awards. He never sought aggrandisement and gave his time unstintingly to his students and trainees, and was an outstanding teacher and clinician. He spent 1962 in London working with Ashley Miles at the Lister Institute. Many young doctors who trained under him went on to brilliant careers. These included four Aberdonians—Bruce Bennett, Charles Forbes, Derek Ogston, and Colin Prentice.

Oscar was humane and kindly, loved his work, and enjoyed music, books, history, Sherlock Holmes, Gilbert and Sullivan, and the Cleveland Indians baseball team. He was an inveterate punster, once writing to a journal: “Dear Sir, I read with pleasure Scott F Gilbert’s paeon to punning in the autumn issue of Perspectives in Biology and Medicine (vol 28, p 148). But, alas, one of his examples was misspoken. The reluctant person who would not join the surfers really said, ‘He also surfs who only stands and wades.’”

He is survived by his wife of 63 years, Marian, and two children.