(Circulation. 1997;95:2338-2339.)
© 1997 American Heart Association, Inc.
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Thomas W. Smith, MD
1936-1997
Boston, Mass
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Thomas Smith
was born in Akron, Ohio. He entered Harvard University in 1954, thus beginning an intense, 43-year relationship with this institution. After graduating from Harvard College in 1958 with an AB degree, cum laude, in chemistry, he served for 3 years as a line officer in the US Navy. He then entered Harvard Medical School, from which he graduated in 1965, magna cum laude. Dr Smith spent 9 years at the Massachusetts General Hospital, serving successively as an intern and resident in medicine and as a cardiology Fellow; he then joined the Harvard faculty and was promoted to Professor of Medicine in 1979. In 1974, he became Chief of the Cardiovascular Division at the Brigham and Women's Hospital, and in 1982 he received an additional appointment as Professor of Medicine, Harvard–Massachusetts Institute of Technology Division of Health Sciences and Technology.
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Dr Smith was an extraordinarily gifted and creative investigator. His first article, based on work performed as a medical student in collaboration with Dr James Adelstein on the radiolysis of pancreatic RNA, was published in Radiation Research in 1965. In the late 1960s, while a research Fellow at Massachusetts General Hospital, he (together with Haber and Butler) developed a novel technique for radioimmunoassay of digitalis, one of the most widely used drugs in cardiovascular medicine. This radioimmunoassay made it possible for the first time to measure blood concentrations of digitalis and facilitated the safe use of this important drug. His article on radioimmunoassay of digitalis, which was published in The New England Journal of Medicine, has become an often-cited classic. The article was accompanied by an editorial, which stated that it "achieved the goal of placing digitalis therapy on a basis that is rational and scientific." Dr Smith's radioimmunoassay of digoxin has become standard and is used worldwide. As a consequence of Dr Smith's contribution, the incidence of digitalis toxicity, previously a common and sometimes lethal complication of digitalis use, has been reduced markedly.
Dr Smith remained interested in and played a key role in advancement of the understanding of the use of digitalis for almost 3 decades after publication of this seminal article. He developed the novel idea that the toxicity of digitalis could be reversed with digitalis antibodies. In 1976, a 39-year-old man, who had taken 90 digitalis tablets with suicidal intent and was dying of refractory cardiac arrhythmia, was successfully treated with the anti-digitalis antibody fragments developed by Dr Smith. The Fab fragment of the antibody has been formulated into a drug called Digibind. Dr Smith initiated the idea of this novel therapy, sustained interest in the concept, and shepherded it through US Food and Drug Administration approval. The therapy repeatedly has proved lifesaving in clinical use. Simultaneously, he began important work on the cellular mechanism of digitalis action and discovered that the molecular target of the drug is Na-K-ATPase on the cardiac cell membrane. He went on to identify the critical role of the Na-Ca exchanger protein in mediating the action of digitalis on cardiac muscle cells. During the past 6 years, Dr Smith capped his contributions to understanding the use of digitalis by playing a leadership role in a large clinical trial of digitalis, the Digitalis Investigation Group (DIG) study, which showed definitively that digitalis reduced the hospitalization rate and deaths from congestive heart failure, thus ending a centuries-old debate.
In the late 1970s, Dr Smith focused his attention in a new direction, the study of myocardial cell biology. He unraveled the molecular pharmacology of cholinergic and adrenergic signaling as well as excitation-contraction coupling. In 1989, he began work on the autocrine and paracrine peptides of cardiac cells. He discovered that endothelin is a positive inotropic agent, and for his work he received a prestigious MERIT Award from the (US) National Institutes of Health.
Dr Smith and his colleague Dr R. Kelly have also produced seminal work on the molecular pharmacology of nitric oxide in cardiac muscle. In 1995, Dr Smith became principal investigator of the new Specialized Center of Research in Heart Failure supported by the (US) National Heart, Lung, and Blood Institute.
In 1996, Dr Smith and his colleagues published an article in the Journal of Clinical Investigation that showed a previously unrecognized secretion of catecholamines in the heart. The editorial accompanying this important article stated that his work "...goes further and more convincingly than any previous work to support the functional significance of an intrinsic cardiac adrenergic system." He also published more than 230 articles in critically peer-reviewed journals, 140 reviews, and several books, including a major text, Cardiovascular Therapeutics, in 1996.
For 22 years, Dr Smith provided exemplary leadership to the Cardiovascular Division of the Department of Medicine at the Brigham and Women's Hospital, where he emphasized all three limbs of the academic tripod. He was a devoted mentor and friend of his faculty and trainees and put his personal stamp of excellence on all of the division's activities. He was a respected, consummate clinician who set the highest standards for clinical care. In addition to his own research, he encouraged the research of others in the division—both faculty and trainees—so that under his leadership the Cardiovascular Division now has respected research programs in almost every area of cardiovascular science, including vascular biology, hemodynamics, cardiac genetics, and cellular signaling. Clinical Research is active in congestive heart failure, myocardial infarction, unstable angina, cardiac transplantation, and electrophysiology. Under the leadership of Dr Smith, the faculty of the Cardiovascular Division grew from 7 in 1976 to 70 in 1997, with 102 research and clinical fellows in cardiology. The Cardiovascular Division's clinical strengths are recognized regionally and nationally, and for the past decade its training programs in academic and clinical cardiology have been deemed to be among the strongest worldwide, attracting the most outstanding research and clinical fellows. This highly esteemed training program and the many leaders in academic cardiology which it has spawned will be one of Dr Smith's most enduring legacies.
Dr Smith played vital roles at the Harvard Medical School, where he served as Chair of the Curriculum Committee and the Council of Academic Societies. He was active in the American Heart Association and chaired both its Scientific Publications and Research Evaluation Committees. He received the AHA's most prestigious awards: the Distinguished Achievement Award and the James B. Herrick Award. He served as President of the Association of University Cardiologists and was for many years a constructive force in the councils of the National Institutes of Health.
The loss of Dr Smith will be keenly felt in the world of academic cardiology. His integrity, the high standards that he set for himself, his colleagues, and his trainees, his enormous sense of responsibility to Harvard University, Brigham and Women's Hospital, the Cardiovascular Division, and his profession will continue to serve as an inspiration to academic cardiologists. In 1996, the Harvard Medical School created the Thomas Smith Fellowship in Cardiovascular Research, which recognizes in perpetuity the area to which Dr Smith devoted so much of his talent and energy: the training of the most promising academic cardiologists.
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