1999 Bristol-Myers Squibb cardiovascular metabolic research award. Earl Davie, PhD, defined the system of blood coagulation.

A scientist whose work with the blood coagulation system led to effective treatments for people with hemophilia is the recipient of the ninth annual Bristol-Myers Squibb Award The prize carries with it a $50 000 award and a silver medallion. In research that spanned more than 4 decades, Dr Davie hypothesized, elucidated, and defined the blood clotting system. His work began as a graduate student, when he showed that the digestive pancreatic protein trypsinogen was converted into an active enzyme called trypsin when a single peptide bond was cleaved. This study served as a model for the coagulation process proposed by Davie and his collaborator , Dr Oscar Ratnoff. As a young researcher at Case Western University in Cleveland, Ohio, Dr Davie studied the blood of people with rare clotting disorders. He discovered than in some cases, blood that would not clot on its own would clot when combined in a test tube with the plasma of a person with normal blood. From this, he predicted that blood that did not clot lacked certain factors that were the signals for coagulation. In 1962 and 1964, Drs Davie and Ratnoff published their theory that coagulation was the result of a series of sequential actions in which proteins in blood plasma are activated from a dormant state. The final result is the production of a fibrin clot at the site of the injury. During the second half of the 1960s and the 1970s, Dr Davie and another collaborator, Dr Kazuo Fujikawa, isolated and purified most of the plasma proteins involved in the sequential cascade of events that is the blood clotting system. They also identified the peptide bonds involved in the cleaving process that activates each factor. With the advent of recombinant DNA technology, Dr Davie collaborated with Dr Dominic Chung in cloning and sequencing the genes for each factor. During this process, they sequenced the full-length gene for hemophilia B. They demonstrated that the variation of even a single nucleotide could result in a severe clotting disorder. When Drs Davie and Chung cloned and sequenced the genes for more than a dozen other clotting proteins, they paved the way for the mass-production of these proteins in mammalian cells. These proteins, used as clotting factors, treat both hemophilia A and B. These clotting factors made by recombinant technology are also safer than factors made from pooled blood products, which can be contaminated …