Elizabeth Barrett-Connor, a colossus in chronic disease epidemiology, died on 9 June 2019. It was especially poignant that Dr. Barrett-Connor died the same day that one of her numerous mentees, Assiamira Ferrara, was giving the American Diabetes Association’s Norbert Freinkel Award lecture for outstanding work in the understanding of diabetes in pregnancy. Among her long list of legacies, the many superstar scientists whom Dr. Barrett-Connor has mentored, and many of whom have modeled themselves after her, will remain a vastly enduring contribution.

Born on 8 April 1935 in Evanston, IL, Dr. Barrett-Connor graduated from Cornell Medical School in 1960 and completed her residency in internal medicine. She saw the importance of science in medicine and went to the London School of Hygiene and Tropical Medicine to train in epidemiology. Elizabeth was as visionary as she was bold, and I recall her telling me about her early challenges going against what was the norm. For example, a senior male physician colleague, reacting to her desire to pursue epidemiology, said, “So, you don’t want to see patients but be counting?” Her reply was, “Yes, I plan to count really damn well.”

Her early work was as an infectious diseases physician and epidemiologist at the University of Miami, where she worked for 5 years. However, serendipity had other plans for her. In 1970, she moved with her husband, Jim, to California, where she joined the faculty of the University of California San Diego (UCSD). It was here where she saw an important new opportunity in lipid research and quickly started the Rancho Bernardo cohort study, a move that would eventually define her as a foremost epidemiologist in the area of chronic diseases.

Throughout her long and productive career at UCSD, Dr. Barrett-Connor was at the forefront of advances in the field of chronic disease epidemiology, and her contributions across the spectrum of diseases are evident in her over 1,000 publications and her place among the highly cited in several topics. She led many important investigations and was a central player in numerous landmark observational and interventional studies. Among her many scientific contributions, her work in the understanding of the role of sex hormones in heart disease and osteoporosis was groundbreaking. But she never rested on her laurels, and always got involved and immersed in new challenges as they arose—diabetes, bone health, aging…you name it.

Dr. Barrett-Connor was a critical thinker and equally creative, and often took positions widely at loggerheads with conventional wisdom, and used any and every bully pulpit to be heard, often proving her position right with time and new data. An illustration of Elizabeth’s forthrightness is her substantial contribution to the evidence for and against hormone replacement therapy (HRT) and heart disease. Her analysis and opinion on this topic, published in an article in the JAMA in 1991, summarizes the motivating force behind the National Institutes of Health (NIH) funding the 600+ million dollar Women’s Health Initiative (WHI) to test the question of whether HRT reduced heart disease. Earlier, Dr. Barrett-Connor was a dissenting voice on a U.S. Food and Drug Administration panel, which would have otherwise recommended heart disease prevention as an indication for HRT, based on the evidence from observational studies. She was adamant that a well-designed trial was essential before an indication was justified, and sure enough, the WHI returned a null finding, affirming the value of Dr. Barrett-Connor’s cautionary principle.

During the planning of the Diabetes Prevention Program (DPP), Elizabeth was outspokenly against including troglitazone as one of the arms in this multicenter trial of diabetes prevention, as data on safety for the drug were scant. What transpired was that this arm was stopped after 14 months as the Data Safety Monitoring Board (DSMB) noted adverse liver side effects. For me, as a young investigator then attending the innumerable DPP planning meetings among the “who’s who” in diabetes, the force of Dr. Elizabeth-Connor’s conviction and her ability to fight the fight and to keep science honest was a lesson to remember.

Dr. Elizabeth Barrett-Connor was a brilliant mind and a force of nature who defied every glass ceiling with her intelligence, grit, boldness, and sheer force of personality. When it came to matters of science, she spared no one, including herself. At a social level, however, Elizabeth was a very warm and generous human being, always caring, and a lot of fun to be around. She has inspired innumerable young minds, a legacy that will immortalize the work and impact of this truly outstanding human being.