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After the United States entered World War I in April 1917, Heidelberger was commissioned as a Lieutenant in the Sanitary Corp of the U.S. Army, and assigned to the Section on Combating Venereal Diseases. His duty there was to conduct research on anti-syphilitics, research which dovetailed closely with the work on the chemotherapy of syphilis he had been conducting with Walter A. Jacobs at the Rockefeller Institute for Medical Research. He was stationed at the Rockefeller Institute, his home institution, which during the war provided training to army physicians in laboratory technique. Heidelberger was under the command of the Institute's director, Simon Flexner, who was also the chief officer of the Section on Combating Venereal Diseases.