The hematology research community recently lost a pioneer. Oscar Ratnoff, MD, died of respiratory failure on May 20, 2008, in Cleveland Heights, OH. He was 91 years old. Ratnoff’s career spanned more than five decades.
Ratnoff was born in 1916 in Manhattan, the son of a prominent Brooklyn pediatrician. He graduated from the Columbia University of Physicians and Surgeons in 1939. After interning at Johns Hopkins Hospital in Baltimore, MD, he did his postdoctoral training at Harvard Medical School and Montefiore Hospital in New York. He served in the U.S. Army during and after World War II, from 1943-1946. Ratnoff joined Case Western Reserve University in Cleveland, OH as a young clinician in 1950. His tenure with the university lasted more than 50 years. It was there that he made his first breakthrough by identifying coagulation factor XII, also called “Hageman” factor for the first patient to be diagnosed with the deficiency.
In 1957, Ratnoff met biochemist Earl W. Davie, PhD, and the two began a collaboration that eventually shed vital new light on the intricacy of the coagulation process. They found that a group of proteins, lipids and calcium functioned in an interconnected, sequential way that led to effective blood clotting. Through a series of laboratory tests, the team discovered that an absence or deficiency of one of the factor proteins could cause bleeding in certain patients. They were also able to explain the role fibrin (an insoluble protein) plays in forming the platelet plugs that are crucial to clotting.
Ratnoff and Davie studied coagulation for several years, describing the process as a “waterfall sequence for intrinsic blood clotting.” Their early findings were first published in 1962 in the journal Biochemistry and then with more elaboration in the journal Science in 1964,. These seminal papers, along with that of British scientist R.G. MacFarland, are considered fundamental to the subsequent treatment advances made for patients with strokes, wounds and bleeding disorders in the decades that followed.
In the 1970s, Ratnoff, with the help of Case Western colleague Theodore Zimmerman, MD, helped develop a more accurate technique for detecting hemophilia carriers. By using an antiserum derived from rabbits and combining it with clotting factor, they established a test with an accuracy level of approximately 95%, compared to the roughly 25% accuracy of prior tests. The technique was particularly useful because it came before the availability of genetic testing. In 1971 the National Hemophilia Foundation gave Ratnoff its Researcher of the Year award.
By the early 1980s, Ratnoff was warning the hemophilia community about the inherent dangers in clotting factor products that were infected with HIV and hepatitis C (HCV). Recognizing how susceptible plasma-derived products from the pooled blood of many commercially solicited human donors were to these viruses, he tried to alert the medical community. Ratnoff noted a drop in lymphocyte counts – often associated with viral infection – among some hemophilia patients and cautioned that it could increase vulnerability to blood-borne pathogens such as HIV and HCV.
Ratnoff’s protestations were initially dismissed by some, who cited the necessity of manufacturing enough factor to supply the hemophilia market, according to Nathan A. Berger, a professor of experimental medicine, biochemistry and oncology at Case Western and a former dean of the medical school. “But ultimately, the medical community and the drug companies came to see his point and favor a single-donor approach,” said Berger. “He was farsighted in that respect, and he had a voice that had to be listened to.”
In the late 1980s and 1990s, Ratnoff remained an active researcher and clinician. He continued to publish scientific papers on topics such as the genetics of factor XI deficiency and gene therapy for hemophilia B.
In 2003, Harold Roberts, MD, a fellow hematologist and longtime colleague painted a colorful picture of Ratnoff in a historical review article in the British Journal of Haematology. “Oscar Ratnoff is, without question, one of the outstanding investigators in the field of coagulation,” Roberts wrote in the piece. “He is well known for his strong opinions, but they have always been based on data. His debates, though sometimes ‘rough and tough’ were always friendly and constructive and frequently entertaining. Those of us old enough to remember Ratnoff and colleagues debating the issues of the day can only reminisce about how much fun it was to hear and listen to these great men describe their discoveries during a golden era of coagulation research.”
Ratnoff is survived by Marian, his wife of 63 years; son William Ratnoff, MD, a rheumatologist from Lubbock, TX; daughter Martha Fleisher of Dallas and five grandchildren.
Source: The New York Times, June 6, 2008