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Born in Camden, New Jersey, in 1858, Howard Atwood Kelly attended the University of Pennsylvania, graduating with a bachelor's degree in 1877 and his M.D. in 1882. In 1889, he became the first professor of gynecology and obstetrics at the Johns Hopkins University launching a 30-year career at the school.

Kelly is remembered—along with William Osler, Professor of Medicine, William Stewart Halsted, Professor of Surgery, and William H. Welch, Professor of Pathology—as one of the "Big Four" founding professors at Johns Hopkins Hospital. He was called a "wizard of the operating room" and was an early user of radium to treat cancer.