Dr Caroline Bedell Thomas, a pioneer in the study of hypertension and preventive medicine, died on December 14, 1997, at the age of 93. A remarkable physician, investigator, and educator, she contributed much to our knowledge of hypertension and risk factors for cardiovascular disease early in life. A native of Ithaca, NY, she graduated summa cum laude from Smith College in 1925. She performed graduate work in the Department of Biology at the Johns Hopkins University (1925–1926) and subsequently studied for her doctor of medicine degree at the Johns Hopkins School of Medicine (1926–1930). Following house staff training at the Johns Hopkins Hospital, she was a postdoctoral fellow in neuropathology (1933–1934) under the direction of Dr Stanley Cobb at Harvard University and a postdoctoral fellow in physiology (1934–1935) under the direction of Dr Philip Bard at Johns Hopkins. In 1935 she joined the faculty at the Johns Hopkins School of Medicine, where she focused her attention on the study of neurogenic models of hypertension as well as the effects of sympathectomy on blood pressure. Dr Warfield T. Longcope, who was her mentor and Chair of the Department of Medicine, invited her to start an adult cardiac clinic. With characteristic energy and determination, she organized a clinic where provision of high-quality care was complemented by an equally strong commitment to research focused on the treatment and prevention of disease. Extrapolating from studies in mice, she conducted a pioneering 4-year investigation in which she and Dr Richard France demonstrated that prophylactic administration of sulfa drugs prevented streptococcal infections and acute rheumatic fever in patients who were susceptible to rheumatic fever. On the basis of these and subsequent findings with the United States Navy, more than a half million soldiers received prophylactic sulfadiazine during World War II. In 1957, she was awarded the James D. Bruce Memorial Award for her contributions to the prevention of rheumatic fever.
In the early 1940s the infectious model of disease causality was at its peak. This aroused great hope that chronic diseases could be eliminated by identification of a single underlying cause which could, in turn, be cured by application of a single treatment. In contrast, Dr Thomas anticipated more modern concepts of disease causality. She proposed a “kaleidoscopic” psychobiological model for chronic diseases, in which many factors led to an early preclinical phase of disease that could later manifest as a clinical complication. She felt the particular configuration of factors in each individual would determine the natural history of the disease. To test this hypothesis, she designed and initiated a long-term natural history study that she named the Precursors Study. The principal aim of the study was to identify youthful precursors of hypertension and coronary heart disease (or both) by recording a broad range of demographic, physiological, psychological, and metabolic characteristics in medical students at their admission into the Johns Hopkins School of Medicine. Starting with the class of 1948, she characterized 1337 school entrants between 1948 and 1964 by collecting information on more than 2000 variables for each individual. She also began an annual follow-up of the cohort aimed at linking these variables to the subsequent occurrence of disease during later life. Follow-up continues to the present day, making the Precursors Study one of the oldest continually functioning longitudinal investigations in existence. In the early years, Dr Thomas had to contend with a mix of peer indifference and even frank opposition on the part of some colleagues, who felt it was improper for her to continue full-time employment while raising a family. During this period, she was buoyed by her vision of the future, by her resolute work habits, and by the support of colleagues whom she most admired. The latter included Dr Irvine Page and many other close associates in the Council for High Blood Pressure Research, whose fall meetings she attended with regularity during the era when they were held in Cleveland, Ohio.
Reflecting her lifelong interest in high blood pressure, she included the cold pressor test, salt loading, and several other blood pressure stressors as part of the Precursors Study. She also used the Precursors Study to examine the relationship of blood pressure in the cohort to parental history of hypertension. Her perseverence paid off with the publication of more than 130 Precursors Study manuscripts in peer-reviewed journals. These covered a wide range of topics, from risk factors for cardiovascular disease to the study of predictors for depression, suicide, and malpractice suits. Results from the Precursors Study vindicated her belief that cardiovascular disease in adults was the late manifestation of a process that began much earlier in life and that it resulted from the effects of many risk factors, including high blood pressure, high levels of blood cholesterol, physical inactivity, and a family history of cardiovascular disease.
Dr Thomas was also an active participant in discussions of the etiology of hypertension and coronary heart disease. In 1964 she was moderator for a lively debate between Sir George Pickering and Robert (later to be Sir Robert) Platt concerning the heredity of hypertension at the International Symposium on the Epidemiology of Hypertension.
I did not meet Dr Thomas until she was in her eighties, but even at that relatively advanced age one had to marvel at her intellect, organizational skills, and determination. She stepped down as director of the Precursors Study in 1984, but she continued to be actively involved in the study and for many years served on its advisory board. She maintained a lifelong commitment to the study of science and continued to publish scholarly papers until shortly before her death. In the latter part of her life she was very gratified to know that her vision in starting the Precursors Study had been justified. She was also very pleased that the study was moving into its most productive phase under the direction of her successors as director of the study (Dr Thomas Pearson, 1984 to 1988, and Dr Michael Klag, 1988 to present). During her lifetime, Dr Thomas influenced many younger colleagues, always encouraging them to pursue their profession with the seriousness of their predecessors. As a reminder of this legacy, she preserved many historical treasures, including the chair used by Osler as he toiled on the first edition of his Textbook of Medicine. She leaves a rich legacy of contributions as a scientist, educator, and role model in the field of high blood pressure.
Paul K. Whelton, MD, MSc
Professor of Epidemiology and Dean
School of Public Health and Tropical Medicine
New Orleans, Louisiana