There should be, and in the best of cases there is, a synergy between basic research and patient care. However, this synergy is hard to develop because the techniques required to be a successful researcher are so different from the skills required to be an outstanding physician. Harold R. Roberts, M.D., of the University of North Carolina at Chapel Hill, is an example of a physician-researcher who has benefited from having his feet in both the world of patient care and the world of the laboratory: he has let clinical problems direct his basic research effort and conversely has adopted research advances in his care of patients. Dr. Roberts's long and continuing career has included many research and clinical advances. He was part of the first group to determine the amino acid sequence of the important thrombin inhibitor hirudin and part of the group that prepared the first cryoprecipitates which were the first alternative to plasma as therapy in hemophilia A. Dr. Roberts has made significant advances in understanding the protein chemistry behind hemophilia B; he was among the first researchers to identify some patients as not being completely deficient but instead as having measurable levels of protein and subsequently demonstrated that this protein was dysfunctional. This important advance led him to a classification scheme for patients into Cross Reacting Material (CRM) positive, negative, and reduced. Dr.

Serpins (serine protease inhibitors) are a superfamily of proteins whose physiologi- cal action is primarily targeted to inhibiting serine proteases. There are instances where serpins are not inhibitors (and can carry steroid hormones for instance), yet key structural and functional elements found in all serpins are maintained in these 'non-inhibitor' ser- pins. Many serpins have well-described biological properties which influence pathophysi- ological events, including: antithrombin (historically called antithrombin III), ai-protease inhibitor (historically called ai-antitrypsin), and plasminogen activator inhibitor-I, just to mention a few. A deficiency or defect in antithrombin leads to venous thromboembolic disease, while a deficiency or defect in ai-protease inhibitor is associated with chronic obstructive pulmonary emphysema. In contrast, it has been suggested that increased levels of plasminogen activator inhibitor-l may be a predisposition to myocardial infarction. The list goes on for each of our own "favorite" serpin. The biological roles found for serpins are key participants in almost every physiological event. In other words, serine proteases are needed for many events in biology and the role of serpins to down regulate these pro- teases is essential. Thus, just using these three examples above for serpins and their patho- physiological roles reminds us that the medical costs to control such events is significant worldwide.

There should be, and in the best of cases there is, a synergy between basic research and patient care. However, this synergy is hard to develop because the techniques required to be a successful researcher are so different from the skills required to be an outstanding physician. Harold R. Roberts, M.D., of the University of North Carolina at Chapel Hill, is an example of a physician-researcher who has benefited from having his feet in both the world of patient care and the world of the laboratory: he has let clinical problems direct his basic research effort and conversely has adopted research advances in his care of patients. Dr. Roberts's long and continuing career has included many research and clinical advances. He was part of the first group to determine the amino acid sequence of the important thrombin inhibitor hirudin and part of the group that prepared the first cryoprecipitates which were the first alternative to plasma as therapy in hemophilia A. Dr. Roberts has made significant advances in understanding the protein chemistry behind hemophilia B; he was among the first researchers to identify some patients as not being completely deficient but instead as having measurable levels of protein and subsequently demonstrated that this protein was dysfunctional. This important advance led him to a classification scheme for patients into Cross Reacting Material (CRM) positive, negative, and reduced. Dr.