In Memoriam: Darrell R. Abernethy 1949–2017

Abstract

We lost Darrell Abernethy on November 18, 2017 – two weeks after his 68th birthday. He was a fixture in the clinical pharmacology community for 40 years. Just two months before his passing, Darrell was with us at the September 2017 Annual Meeting of the American College of Clinical Pharmacology. He was his usual laid-back, understated, grinningly cynical self. Now he is gone. Darrell was a native of Beloit, Kansas – population about 4000. His Beloit High School Class of 1967 had some 60 graduates. With such small numbers, the school could field only a 6-man football team – Darrell was a 2-way star. From high school Darrell went on to the University of Kansas, where he received his undergraduate degree, and ultimately his combined M.D. – Ph.D. degree in 1976. His Ph.D. work, done under the mentorship of Dan Azarnoff, dealt with drug effects on cholesterol biosynthesis, and was published as papers in Steroids and in Biochemical Pharmacology. Darrell was 28 years old at the time. Darrell moved to Miami to do his internal medicine clinical training at Jackson Memorial Hospital and the University of Miami. In that two-year period, he saw, in his words, “some pretty gritty stuff.” Meanwhile, he became a lifelong Miami Dolphins fan. Inspired by Dan Azarnoff, Darrell developed a determination to become a clinical pharmacologist, and embraced the discipline with a tenacity that remained undiminished over the next 4 decades. He moved to Boston where he trained at Tufts University School of Medicine as a postdoctoral fellow for 2 years, followed by 2 years on the faculty as an assistant professor. During those years, one of us (DJG) worked with him literally every hour of every day, leading to a close professional and personal bond. His research work was intense and relentless, yielding some 80 original research publications, as well as many more reviews, editorials, chapters, and commentaries. His work touched several areas of clinical pharmacology – age and gender effects on drug disposition, pharmacokinetic drug interactions, and drug uptake into the central nervous system. Darrell's studies on drug distribution and clearance in obesity are of lasting impact on the field. He clearly demonstrated that drug distribution and drug clearance are independent entities, working in concert to determine elimination half-life. He thereby dispelled the notion that drug distribution depends on elimination. Darrell was of course a recruiting target for medical schools and hospitals across the country. In 1983 he moved to Baylor College of Medicine, joining their hypertension and clinical pharmacology program under the direction of Jerry Mitchell. On his first try, Darrell was awarded his first R01 grant in support of further basic and clinical studies of drug disposition in obesity. His next professional stop was Brown University and Rhode Island Hospital (1986–1994), then Georgetown University and Medical Center (1994–1999). Each stop in his professional career was marked by astounding research productivity, and a personal leadership style and work ethic that energized and inspired his colleagues and trainees to maximize available opportunities for personal skill development as well as service to the scientific community. Darrell moved to the public sector in 1999, serving as Chief of the Laboratory of Clinical Investigation (LCI) for the National Institute on Aging from 1999 to 2007. The LCI is a diverse lab, and he supervised its 3 major sections consisting of bioanalytical chemistry and drug discovery, diabetes, and magnetic resonance imaging and spectroscopy. His own lab continued research into calcium channel antagonists and the role of splice variants on the biophysical properties of calcium channels. Always looking for new and better methods to add insight into pharmacological systems, Darrell also explored the application of neural networks for antiplatelet pharmacodynamics, utilized wavelet and Fourier transforms in pharmacological imaging and heart rate variability analysis, and introduced the drug burden index for assessing the burden of medications in the elderly. Darrell was a post-doctoral advisor to one of us (DEM), and he is remembered as an outstanding mentor, a role that he took very seriously. He led by example, guided and inspired so many, and represented the ideal in what it means to be a mentor and leader. After a stay as Chief Scientific Officer of the United State Pharmacopeia (2007–2009), Darrell assumed his most recent position as Associate Director for Drug Safety in the Office of Clinical Pharmacology in the Food and Drug Administration. In the Office of Clinical Pharmacology, Darrell played the role of a senior adviser, and was a person who never hesitated to speak his mind. He took on numerous interns and fellows, and enjoyed the challenges of new therapies and technologies. In the later stages of his career, Darrell's research and writings took on clinical pharmacology issues and problems in a broader context: the drug burden index as it emerged as a predictor of adverse drug reactions, particularly in the elderly; and the use of systems analysis approaches to understand the risk of drug interactions and drug toxicity. Had Darrell lived to pursue and develop these ideas further, the benefit to the scientific community and the public health in general would have grown in parallel. The many years of creativity left in his mind were cut short by his failing health. A final striking feature of Darrell's life was how often he was sought after by his colleagues and peers to serve as a leader and advisor. His style was no-nonsense and no-frills. He rendered his opinions and assessments honest and concisely, yet always good-naturedly and with a tinge of cynical humor. His leadership positions over the years are too numerous to present in full, but by way of example he served as President of the American Society for Clinical Pharmacology and Therapeutics (ASCPT), President of the United States Pharmacopeial Convention, and Chair of the American Association for the Advancement of Science. He was Editor-in-Chief of Pharmacological Reviews and of Pharmacology Research and Perspectives, and served on the editorial boards of many other scientific journals. Over the years he chaired numerous NIH study sections and review committees. He received the Rawls-Palmer Progress in Medicine Award as well as the Abrams Award in Geriatric Clinical Pharmacology from ASCPT, and the Nathaniel T. Kwit Distinguished Service Award from the American College of Clinical Pharmacology. No doubt many other recognitions and honors were in his future had he lived into his senior years. Many of us witnessed Darrell's extraordinary dedication to the discipline of clinical pharmacology at the recent 2017 Annual Meeting of the American College of Clinical Pharmacology in San Diego. Despite his deteriorating health, Darrell developed and co-chaired a scientific symposium on biosimilars, where he presented on biosimilar interchangeability, an area in which he again provided ground-breaking scientific leadership by contributing to the establishment of the FDA's regulatory framework in this emerging field of clinical pharmacology. Darrell was not all work. He had great affection for his Labrador Retrievers. He was a sailing enthusiast, and embraced the gadgetry, jargon, and swagger of the mariner. At his last ACCP Annual Meeting in September of 2017, Darrell took particular delight in watching the boats in the San Diego bay at dinner. He loved tractor pull competitions, and never missed an episode of The Dukes of Hazzard. He was always fit and trim, and was religious about his exercise program. What I remember vividly are holiday dinners at his home or mine, hiking to exhaustion in the White Mountains, hours spent on the bay waters of Rhode Island, and pre-dawn runs through the streets of inner-city Washington. We will miss him terribly.