Educated at the Brooklyn Polytechnic Institute where he studied engineering, Jelliffe's true interests were in botany, zoology and geology. After graduation he proceeded to study medicine at Columbia University's College of Physicians and Surgeons, obtaining his doctorate in 1889. He worked at St. Mary's Hospital in Brooklyn for a time before traveling to Europe. In 1896, he met and befriended William Alanson White, and the two would go on to collaborate on a number of projects in the following years. In 1907, while attending the Amsterdam congress, he met Carl Jung who influenced Jelliffe in his interest in Freud's work. Later that year, he became Clinical Professor of Mental Diseases at Fordham University. In 1913, together with White, he founded Psychoanalytic Review and published The Modern Treatment of Nervous and Mental Diseases, an important work that went through numerous editions. Jelliffe was a pioneer in psychosomatic medicine and many of his papers on the subject were collected in Sketches in Psychosomatic Medicine (1923). Although Jelliffe eventually abandoned Freudian theory, he nevertheless remained on friendly terms with Freud. Jelliffe was a prolific writer and produced over 400 scientific articles and numerous translations during his career. He held a variety of posts in the field including president of the New York Psychiatric Society, the American Psychopathological Society and the New York Neurological Society. His other works include Technique of Psychoanalysis (1920) and Disease of the Nervous System (1929).
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