William A. Muller was born in Manhattan but grew up on Long Island; he is the oldest of three brothers, among whom might be found typical sibling rivalry. He is of Jewish ancestry, but his parents and his extended family are not especially observant. Muller had a childhood fear of dying that led him to want to "cure death;" he began to think of medicine as a career from that early age. He did well in school, being salutatorian in his high school. He believes, though, that his youngest brother is the most intelligent, and he discusses Toby's academic career. When Muller entered Harvard University he was shocked at the intense level of competition there. He describes his undergraduate curriculum and his experience purifying DNA under lab director Lynn C. Klotz. He also ran track and cross country. During his college summers he participated in a vaccination project in Central America. Feeling that clinical and research work should complement each other, Muller chose to attend the Rockefeller University-Cornell University Medical College MD/PhD program. At that time the draft was still an important factor in Muller's life. David Baltimore came to Rockefeller at this time, and transformed the nature of the Rockefeller community. Muller decided to work in the Zanvil A. Cohn/James Hirsch lab, where he actually worked with Ralph M. Steinman on endocytosis-iodination techniques. He explains showing that membrane recycles and describes the reaction of the scientific community. He talks about his clinical training in medical school and the practical nature of medical education. He accepted a residency at Massachusetts General Hospital and began a pathology residency at Brigham and Women's Hospital. Muller talks about his social life during medical school and residency; how residencies differ; how clinical experience enhances research; the empirical nature of medicine; and the importance of basic research. He studied endothelial cells in the Michael A. Gimbrone, Jr., lab, showing that angiotensin converting enzyme is apically polarized. His experimental methods included testing the validity of the data on slaughterhouse aortas. He took a monoclonal antibody approach and brought biochemical expertise to the Gimbrone lab. Muller discusses his work examining how leukocytes bind to endothelial cells and his fellow Pew scholars who work on endothelial cells. His research on cell adhesion molecules led to his discovery that PECAM-1 is required for transendothelial migration of leukocytes; this discovery may have clinical application. He continued researching multiple functions of PECAM and searching for unknown adhesion molecules. Although he was anxious at first about returning to his first graduate-school lab, Muller accepted a position at Rockefeller University and in pathology at Weill Cornell Medical College. His first grant application rejected, Muller shifted the focus of his research; he now studies proteins that mediate monocyte binding and transmigration. Muller concludes his interview with a discussion of the process of scientific discovery, especially as he experienced it while establishing the role of PECAM in endothelial cell adhesion; and an explanation of the significance of the Pew Scholars in the Biomedical Sciences award and the RJR Nabisco Research Scholars Award in his career development.
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