|Image drawn by Dot Roberson. Image courtesy of The FASEB Journal, www.fasebj.org.
Ronald “Ron” Winfield Estabrook, a world-renowned biochemist with a special knowledge of enzymatic reactions related to toxicology and steroid hormone biosynthesis, died at his home Aug. 5. He was 87 and had suffered from congestive heart failure.
An expert in the field of cytochrome P450 biochemistry and biophysics, Estabrook helped transform the University of Texas Southwestern Medical School, as it was called in his day, into a powerhouse. Under his leadership, the biochemistry department became the mecca of cytochrome P450 studies, pushing the field forward from its modest initial findings to become one of the most influential research subjects in biomedicine.
Born in Albany, N.Y., on Jan. 3, 1926, Estabrook attended public schools. He graduated from Albany High School in 1943 and that July joined the U.S. Navy. He attended officer training schools at Princeton and Notre Dame and was appointed to the rank of ensign in March 1945. He was assigned subsequently as a line and gunnery officer on a minesweeper and participated in the Allied occupation of Okinawa Island and Japan.
After World War II, Estabrook earned his undergraduate degree from the Rensselaer Polytechnic Institute in 1950 and pursued graduate training in biochemistry at the University of Rochester under the mentorship of Elmer Stotz, completing his dissertation, “Studies on the Cytochromes in Heart Muscle Extracts,” in 1954.
Estabrook then began a long association with the Johnson Foundation at the University of Pennsylvania. He began as a postdoctoral fellow with Britton Chance, during which time he learned sophisticated spectroscopic techniques as they were applied to studies of mitochondrial electron transport. He concluded his time at the foundation as its deputy director. During his tenure at Penn, he spent a sabbatical at the Molteno Institute at Cambridge University with David Keilin, the discoverer of cytochromes. In 1959, Estabrook joined the faculty of the University of Pennsylvania School of Medicine, where he advanced to the rank of professor of physical biochemistry while remaining a member of the Johnson Foundation faculty.
In the early 1960s, Estabrook, together with David Cooper and Otto Rosenthal of the University of Pennsylvania department of surgery, performed pioneering experiments that resulted in the discovery of the functional properties of a unique hemoprotein species, now known as cytochromes P450, and proved their roles in the metabolism of steroids and drugs.
The technique, originally used by Otto Warburg in showing that cytochrome oxidase (Atmung’s ferment) was the terminal oxidase in the mitochondrial respiratory chain and known as a photochemical action spectrum (figure 1), was applied to preparations of endoplasmic reticulum, called microsomes. The technique involved reversing the CO inhibition of either drug metabolism or steroid hydroxylation activity of the cytochrome P450 by specific wavelengths of light. The wavelength at which the CO adduct of the enzyme demonstrated the maximum absorption of light and the maximal reversal of the CO inhibition was 450 nanometers, thus the name of this class of enzymes.
The significance of these oxygenating cytochromes P450 in toxicology, environmental health and endocrinology is immeasurable, and the determination of their functional importance was a fundamental discovery. For these studies, Estabrook was elected to the National Academy of Sciences and later, for his contributions to the field of medicine, to the Institute of Medicine of The National Academies. He also was awarded a Doctorem Medicinae Honoris Causae from the Karolinska Institutet in Stockholm.
Estabrook was the first of a number of basic science chairs who were recruited to UT-Southwestern under the direction of Donald Seldin, then chairman of medicine, and Charles Sprague, then dean of the medical school. He arrived in 1968 to serve as the Virginia Lazenby O’Hara professor of biochemistry and chairman of the biochemistry department.
Estabrook recruited four young assistant professors at that time, of which I was one, and forged ahead with a tour de force as he hired more faculty members over the next few years to fill out his roster. The biochemistry department became a hub for cytochrome P450 studies, as numerous scientists from throughout the world spent sabbaticals in Dallas to pursue biophysical and biochemical studies of these all-important enzymes. The evolution of the cytochrome P450 field is legendary, and it is not possible to read about the side effects of any therapeutic drug without mention of the role of these enzymes in the context of drug-drug interactions. During his 14 years as a chairman, Estabrook built a world-class center of research revolving around the cytochromes P450 and their biological and biophysical properties. During this period, Estabrook also served as the first dean of the Graduate School of Biomedical Sciences.
Not only was Estabrook an outstanding mentor of faculty members, having nurtured the careers of a number of future department chairs including Thomas E. Smith (Howard University), Louis B. Hersh (University of Kentucky), Michael R. Waterman (Vanderbilt University), Russell A. Prough (University of Louisville) and me (Medical College of Wisconsin), but he also was a prime mover in the founding of several societies and associations, including the Association of Medical and Graduate Departments of Biochemistry and the International Society for the Study of Xenobiotics. He was the charter treasurer of The Academy of Medicine, Engineering and Science of Texas when it was founded in 2004. He served as treasurer of the American Society for Biochemistry and Molecular Biology from 1985 to 1991.
Estabrook was well known for the insightful questions he always asked and for his incredible ability to sum up at the end the important messages of talks at innumerable scientific meetings. He loved to challenge speakers regarding the meaning of their studies. After his retirement in 2006, when he was named the Ashbel Smith professor emeritus of biochemistry, he kept busy with his many avocations, including photography, genealogy, stamp collecting, and traveling and still attended scientific meetings on occasion.
But most of all he will be remembered for his tender heart, his support of the underdog, and his unending support of those whom he had a role in training or with whom he collaborated. For these reasons, he became known to many of us as “Uncle Ron.”
for a list of articles authored by Ron Estabrook in The Journal of Biological Chemistry.
He is survived by his wife of 66 years, June Elizabeth Templeton Estabrook of Dallas, as well as his children, Linda Ann Estabrook Gilbert of Charlotte, N.C.; Laura Elizabeth Estabrook Verinder of Schertz, Texas; Jill Kathleen Estabrook Wisehart of Denver; and David Edward Estabrook of Dallas. Ron was proud of his extended family and shared much of his leisure and travel time with his seven grandchildren and five great-grandchildren, often including his family members on trips abroad. Those of us who were fortunate enough to be touched by his generosity as well as his guidance will miss him greatly.
Bettie Sue Masters (firstname.lastname@example.org) holds the Robert A. Welch Distinguished Chair in Chemistry in the biochemistry department at the School of Medicine at the University of Texas Health Science Center in San Antonio.