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Oates recalled as iconic leader, physician, scientist

Aug. 1, 2019, 10:16 AM

 

John Oates, MD, former chair of Vanderbilt’s Department of Medicine and founder of the Division of Clinical Pharmacology, died this week at 87. (photo by John Russell)

by Bill Snyder and Leigh MacMillan

John Oates, MD, an internationally known physician at Vanderbilt University School of Medicine and a founding father of the discipline of Clinical Pharmacology, died Tuesday (July 30) in Nashville after a short illness. He was 87.

Dr. Oates, the Thomas F. Frist Sr. Professor of Medicine, founded the Division of Clinical Pharmacology at Vanderbilt in 1963 as a joint division of the Departments of Medicine and Pharmacology. He chaired the Department of Medicine from 1983 to 1997.

“The Vanderbilt family is mourning the loss of an international leader in medicine. Dr. Oates will be remembered for his vision and for establishing the innovative and collaborative approach used now for clinical pharmacologic research,” said Jeff Balser, MD, PhD, President and Chief Executive Officer for Vanderbilt University Medical Center and Dean of the Vanderbilt University School of Medicine.

“John’s legacy includes countless trainees and associates who have gone on to make incredible contributions to medicine and science as well. On behalf of the Medical Center I want to express my deepest sympathy to John’s wife, Meredith, and his family.”

In the laboratory, Dr. Oates made fundamental contributions to current understanding of the effects of aspirin on prostacyclin and thromboxane and platelet function. His publications have been cited more than 36,000 times.

“It is impossible to quantify the impact of John Oates on this institution,” said Nancy Brown, MD, the Hugh Jackson Morgan Professor and current chair of Medicine at Vanderbilt. “Our strengths in personalized medicine and clinical and translational science stem from a vision and a groundwork that he laid many years ago.”

Dr. Oates “promoted a culture of collaboration across departments and valued mentorship,” added Brown, a former division director of Clinical Pharmacology. “John had an incisive intellect. He always managed to ask the consequential question. He did so politely and kindly, and thus drove those around him to reach higher.”

“John Oates was passionate about his family, sailing, his trainees and science,” said Dan Roden, MD, former division director of Clinical Pharmacology who holds the endowed Sam L. Clark, MD, PhD Chair in the School of Medicine and is senior vice president for Personalized Medicine at Vanderbilt University Medical Center.

“I owe my career to him since he hired me as a fellow in Clinical Pharmacology (in 1978) when I had no research experience,” Roden said. “He had a huge impact, not only on many careers, but also through his science on how we prescribe medicines and how we develop new ones.”

“Early in his career at Vanderbilt, John understood the importance of training investigators who could work credibly in both the basic science and clinical space to solve critical problems in the treatment of disease,” said Alastair J.J. Wood, MB, ChB, professor of Medicine, emeritus.

“It was because of that recognition that he designed the Division of Clinical Pharmacology to be a bridge between the basic science department and the clinical department,” said Wood, a former assistant vice chancellor for Research at Vanderbilt.

“Throughout his academic life he promoted that concept of the clinical investigator and many of his former trainees went on to replicate that model throughout the world,” he added. “John Oates’ impact has been enormous on the health of patients throughout the world but also in Middle Tennessee.”

A native of North Carolina, Dr. Oates earned his bachelor’s degree in 1953 from Wake Forest College (now Wake Forest University) and his medical degree from the college’s Bowman Gray School of Medicine three years later.

He received clinical training at the New York Hospital-Cornell Medical Center and research training at the National Heart Institute in Bethesda, Maryland, where he was a clinical associate and senior investigator.

In 1959 he and his colleagues observed that a drug called methyldopa appeared to lower blood pressure. At the time there were no effective treatments for severe hypertension, which increases the risk of stroke, heart attack and kidney failure. Methyldopa, developed and marketed as Aldomet by Merck, became the first.

It was in this dynamic and uniquely productive environment — where discoveries and approaches from the laboratory were applied to clinical research — that Dr. Oates’ vision for clinical pharmacology germinated.

After joining the medical school faculty at Vanderbilt in 1963, he established one of the nation’s first divisions of clinical pharmacology and directed the division for the next 25 years.

“John Oates was a pioneering investigator who elucidated mechanisms of drug action, physiology and disease with imaginative studies in humans based on precise, quantitative methodology,” said Garret A. FitzGerald, MD, FRS, director of the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

“His focus on experimental medicine has become fashionable again in the era of translational science,” said FitzGerald, who trained under Dr. Oates and succeeded him as the Clinical Pharmacology division director. “John’s legacy is carried on by those of us fortunate enough to have benefited from his training.”

Among Dr. Oates’ many discoveries, those in the field of prostaglandin biology are most noted. Prostaglandins are members of a large family of molecules called eicosanoids that are derived from fatty acids, predominantly arachidonic acid, and which have varied and profound physiological and pathophysiological effects.

The Oates team defined the role of prostaglandins in renin release by the kidney, demonstrating the importance of prostaglandins as a pathway parallel to the adrenergic nervous system in controlling renin release and regulating blood pressure.

Dr. Oates also had a long-standing interest in free radicals and oxidative stress, including compounds known as isoprostanes and isolevuglandins, which were discovered at Vanderbilt by his collaborator, L. Jackson Roberts II, MD, professor of Pharmacology, emeritus.

Isolevuglandins and other reactive aldehydes can damage proteins and promote disease, said MacRae F. Linton, MD, the Stephen Schillig Jr. and Mary Schillig Professor of Medicine and director of the Vanderbilt Lipid Clinic and the Atherosclerosis Research Unit.

In recent years Dr. Oates and his collaborators pursued clinical development of small-molecule scavengers of these reactive molecules to treat diseases driven by oxidative stress including Alzheimer’s disease, hypertension and coronary artery disease.

“John Oates had a tremendous impact on my career, inspiring me to pursue research as a medical resident and recruiting me back to Vanderbilt in 1993,” Linton said.

“Dr. Oates created a community that made all feel welcome,” added Medicine Chair Nancy Brown, MD, who completed her specialty training at Vanderbilt and joined the faculty in 1992.

“He and his wife, Meredith, hosted four dinners each July to enable incoming residents to meet in small groups with the faculty. As a physician-scientist and leader of American academic medicine, Dr. Oates inspired numerous trainees to pursue a career in research,” she said.

Dr. Oates’ first chief resident in Medicine, Barney Graham, MD, PhD, diagnosed one of the first two AIDS cases in Tennessee in 1982. Today Graham is deputy director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases.

“He made my career possible,” said Graham, who as a Vanderbilt faculty member directed the Vanderbilt AIDS Vaccine Evaluation Unit. “The opportunities and guidance he provided when I was a junior faculty member were instrumental in my development as physician-scientist.”

Another former colleague, Raymond DuBois, MD, PhD, former director of the Vanderbilt-Ingram Cancer Center, is now dean of the College of Medicine at the University of South Carolina in Charleston.

“I will forever be grateful to John Oates for launching my career in academic medicine,” DuBois said. “Throughout my 16-year tenure at Vanderbilt, John was a tremendous mentor. He will always be a role model and will be missed greatly by those he taught and befriended.”

Dr. Oates served as president of the Association of American Physicians, president of the American Federation for Clinical Research and vice-president of the American Society for Clinical Investigation.

He was a fellow of the American Association for the Advancement of Science and the American Academy of Arts and Sciences and a member of the National Academy of Medicine.

Dr. Oates is survived by his wife, Meredith, his children David, Larkin and Jim and four grandchildren. Funeral arrangements are pending.

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