By Harvey J. Weiss, MD

2009-05-01

Yale Nemerson, one of the pioneering figures in the field of blood coagulation during the past 40 years, died suddenly on February 12 while recovering from a long bout of pneumonia. With his passing, the field of hemostasis/thrombosis lost a preeminent scientist who helped to develop the modern theory of blood coagulation in establishing that tissue factor (TF), bound to factor VIIa, is the complex that is uniquely responsible for initiating the pathways leading to thrombin formation.

Dr. Nemerson was born in New York City on December 15, 1931, and attended the Bronx High School of Science. A superb tennis player (in later years, taking lessons from Roy Emerson), he spent a semester as a tennis recruit at Tulane before transferring to Bard College. There, he pursued an interest in the social sciences and arts before electing to enter medical school at New York University, from which he received his MD in 1960. His residency at New York’s Montefiore Hospital led him in 1962 to the laboratory of Theodore H. Spaet, the incubator for many prominent investigators in the field of hematology. Thus began his lifelong study of TF. Although it had long been known to initiate the “extrinsic system,” its precise role in hemostasis was not clear. A well-known scientist once informed him that he did nice work, adding “too bad you study an artifact” — a story that Dr. Nemerson always related with deadpan whimsy. His earliest studies, with Frances Pitlick, were to demonstrate the tight association of TF to phospholipids. In the early 1970s, Dr. Nemerson, in a series of collaborative studies with Jolyon Jesty, Robert Radcliffe, and Sidonie Morrison, proceeded to purify factor VII, develop an accurate method for measuring factor Xa generation, and demonstrate the critical feedback activation of factor VII by factor Xa. These studies provided the means for later kinetic and modeling studies in collaboration with Rodney Gentry. Publications with Ronald Bach and William Konigsberg were the first to describe the purification of bovine TF.

Later, they and other investigators reported the purification of human TF, which led to the cloning of its cDNA, and in 1996, with David Banner and colleagues, to solving a high-resolution crystal structure of the TF: VIIa complex. In collaboration with Vincent Turitto and Cynthia Gemmell, Dr. Nemerson’s group at the Mt. Sinai School of Medicine developed a novel system for studying the kinetics of the TF pathway under flow conditions and shear rates comparable to those in the vascular system. This model allowed his group to present evidence that TF in blood could play a role in the later stages of thrombosis. Dr. Nemerson received many honors throughout his career, including the William Dameshek Prize from ASH in 1977. He was elected to the American Society for Clinical Investigation and the Association of American Physicians and served as chairman of numerous NIH review committees, as well as the Gordon Conference on Hemostasis and Thrombosis in 1978. Dr. Nemerson was elected president of the International Society on Thrombosis & Haemostasis for its 1993 Congress in New York, and he received the Wright-Schulte Memorial Lecture in 1989, the Distinguished Career Award in 1995, and ISTH’s most prestigious award, the Robert P. Grant Medal in 2003.

Dr. Nemerson’s longtime friend and colleague, William Konigsberg, with whom he had an NIH-funded program project that extended more than 30 years, wrote, “Yale’s insights, curiosity, inspirational guidance, and intellectual leadership were responsible for the longevity and success of the endeavor. Yale will be remembered not only for his magnificent contributions to science, but also for his wide-ranging influence on many of his students and peers.”

He was the consummate scientist whose painstaking and imaginative work was seminal in transforming the “artifact” into what Dr. Samuel I. Rapaport, another pioneer in the field, has termed the “prima ballerina” of the coagulation pathway. If current attempts to modify its effects in a variety of clinical conditions prove to be successful, much will be owed to the contributions of Yale Nemerson.

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