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Obituary: Ronald Winfield Estabrook, Ph.D., M.D.(hc) (1926 – 2013), pioneer in the study of Cytochrome P450s

February 02, 2016

Ron EstabrookOn August 5, 2013, Ronald W. Estabrook, Ph.D., M.D. (h.c.) died in Dallas at the age of 87. His renowned scientific career focused largely on the study of cytochrome P450s and drug metabolism. Ron was born in Albany, NY, and at the age of 17 (1943) joined the U.S. Navy, training in the V-12 program at Princeton. Upon graduation from Officer Training School as an ensign (1945), Ron served on a submarine chaser and minesweeper, the latter in minefields of Okinawa and Japan. Upon discharge, Ron attended Rensselaer Polytechnic Institute, graduating with a degree in biology in 1950. He took his graduate training at University of Rochester, supervised by Prof. Elmer Stotz and received his Ph.D. in 1954, with a dissertation entitled “Studies on the Cytochromes in Heart Muscle Extracts.” This work set the stage for more than 55 years of important research studying hemoproteins. Stotz was a well-recognized investigator in the study of hemoproteins and directed Ron to postdoctoral training with Britton Chance at the University of Pennsylvania.

After three years of postdoctoral training in the Chance laboratory where he mastered modern techniques of spectroscopy, Ron became a visiting research fellow in the Molteno Institute, Cambridge University in the laboratory of David Kielin. Kielin had named the hemoproteins in mitochondria as “cytochromes.” Ron’s training by Stotz, Chance, and Kielin set the stage for his independent career. In 1959, Chance recruited him to Penn as Assistant Professor of Physical Biochemistry, and subsequently he achieved the rank of Professor in 1965. It was during this period that Ron made a series of discoveries that solidified his reputation as a pioneer and leader in the study of cytochrome P450s. With his colleagues Otto Rosenthal and David Cooper, he reported the role of a P450 in adrenocortical microsomes in 21-hydroxylation of steroids as a terminal mixed-function oxidase. He showed that this reaction required a P450 using the recently established photochemical action spectrum technology of Warburg. This work was reported in three landmark papers in 1963. In 1967, with colleagues Herbert Remmer and John Schenkman, Ron reported roles of P450s in hepatic microsomes in drug metabolism, including optical measurement of substrate binding. Over the rest of his exceptional experimental career, Ron and colleagues from around the world made many key discoveries on P450s and drug metabolism.

In 1968, his career changed abruptly. Ron accepted an offer to become Chairman of Biochemistry at the University of Texas Southwestern Medical Center in Dallas. He was also named Virginia Lazenby O’Hara Professor of Biochemistry.  He continued his important research in Dallas, while at the same time establishing one of the major biochemistry departments in the world. In 1973, his role at UT Southwestern became more complex with his appointment as Dean of the Graduate School of Biomedical Sciences.  In 1977, having made the essential steps for establishing the  outstanding graduate school which exists at UT Southwestern, he returned to his roles as an investigator and department chair. He served as Chair until 1982 and as an active investigator until 2006 when he became Emeritus Professor.

During his almost 50 years as an independent investigator, Ron trained a large number of young scientists, many of whom are leaders in the study of drug metabolism around the world. Beyond these, Ron hired six young faculty members who became chairmen of biochemistry departments: Bettie Sue Masters (Medical College of Wisconsin), Russ Prough (University of Louisville), Tom Smith (Howard University), Mike Douglas (University of North Carolina), Mike Waterman (Vanderbilt University), and Lou Hersh (University of Kentucky).

Ron received numerous awards recognizing his accomplishments, far too many to name here. As a result we mention those of particular distinction. At University of Texas Southwestern, he was named Cecil H. and Ida M. Green Endowed Professor of Biochemistry in 1990. In 2006, he was named Ashbel Smith Emeritus Professor, and in 2008, one of the six educational colleges for medical students at UT Southwestern was named Estabrook College. Of particular note was being elected to the Institute of Medicine in 1975 and the National Academy of Sciences in 1979. He was the first member of NAS at UT Southwestern, which has now had about 30 members. In 1997, he received the ASPET Bernard B. Brodie Award in Drug Metabolism and the FASEB Distinguished Scientist Award. He worked tirelessly to encourage young scientists in the area to take leadership in the Drug Metabolism Division. He also served as President of the International Society for the Study of Xenobiotics from 1988 – 89. 

For those who have attended scientific meetings with Ron, one memory that we all carry away was his penetrating questions of the speakers’ research. The last meeting that he attended, the North American Regional ISSX meeting in October 2012 in Dallas, he was still asking such questions. Ron was a true pioneer in our understanding of many aspects of P450 and drug metabolism. He will be remembered by all who met him. Our research has surely been enriched and has prospered from his participation. We are grateful we had a chance to know him as a scientist and a friend.

While the above summarizes the exceptional accomplishments of Ron Estabrook as an investigator and leader in biochemistry, his most admirable accomplishment is his commitment to his family. Ron and his wife June have been well known throughout the world as a close and supportive couple. Their family consists of four children, seven grandchildren, and five great-grandchildren. When one looks for mentors and examples of a well-lived life, professionally and personally, Ron Estabrook is a worthy model.

Sumitted by Russell A. Prough, Ph.D. and Michael R. Waterman, Ph.D. 

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