A Brief Historical Review of the Waterfall/Cascade of Blood Coagulation
This article explores some of the events and people involved in unraveling the basic mechanisms leading to the clotting of blood. It also brings to focus the important role that my teachers and colleagues had on my career in research. When I entered college majoring in chemistry I had little idea that I would have an opportunity to become a professor of biochemistry at a major university. This was clearly the result of the excellent advice and encouragement that I received, particularly from my teachers early in my career. As a senior at the University of Washington, I took a course in biochemistry to complete my credit requirements for a B.S. in chemistry. The biochemistry course was taught by Donald Hanahan, an excellent lipid biochemist who understood the importance of a quantitative measurement. I was fascinated by the biochemistry class that Hanahan taught, as well as by a course dealing with the chemistry of natural products. When Hanahan invited me to work in his laboratory on a senior project, I got my first real experience of what it was like to do laboratory research and I enjoyed it. In the fall of 1950, I entered graduate school at the University of Washington and decided to do my thesis research with Hans Neurath to learn something about protein structure and function. Neurath was an excellent teacher, a distinguished protein chemist, and a leader in his field (Fig. 1). He also had high standards and was very demanding of his students. Neurath was originally trained as a colloid chemist at the University of Vienna. Following his postdoctoral training at the University of London in the chemistry department headed by Frederick Donnan, he immigrated to the United States in 1935, where his research interests shifted to protein structure. He then held positions at the University of Minnesota, Cornell University, and Duke University, and in 1950, he joined the University of Washington School of Medicine as chairman of a newly established Department of Biochemistry. His research interest then focused almost entirely on proteases, particularly pancreatic trypsin, chymotrypsin, and carboxypeptidase, because these proteins were available in sizable amounts and could be prepared in high purity. Much of his career then dealt with their structure and function, including their active sites, substrate specificity, their kinetics, amino acid sequence, interaction with inhibitors, and their mechanism of activation. Over the years, Neurath also became well known for his leadership in the publication of scientificliterature,havingfoundedandservedasEditor-in-ChiefofBiochemistryfor30years. In 1990, he founded another new journal, Protein Science, as well as editing several excellent volumes, such as The Proteins initially with Kenneth Bailey and later with Robert Hill.