Dr. Lucy Wills, a British hematologist, worked in India on “pernicious anemia
of pregnancy” which was later found to be caused by folic acid deficiency. Dr.
Yellapragada Subbarow synthesized that vitamin, as well as analogues that blocked its
activities, including the drugs aminopterin and methotrexate. Aminopterin, first used by Dr.
Sidney Farber, induced complete remissions in children with acute lymphocytic leukemia.
Dr. Cornelius P. Rhoads was the U.S. Army Chief of the Medical Division of the Chemical
Warfare Service during World War II. When the war ended, an outstanding group of
scientists and clinicians who had served under him went on to play a major role in the
development of medical oncology. Three of them, Doctors David Karnofsky, Frederick
Philips, and Chester C. Stock, as well as Dr. Joseph H. Burchenal, joined Rhoads at the
Memorial Hospital and Sloan-Kettering Institute for Cancer Research. The Memorial group
developed a broad-scope cancer chemotherapy program that included screening,
pharmacology, clinical investigation of chemotherapeutic agents and liaison with the
pharmaceutical industry. During those years, two other important anticancer drugs were
synthesized: cortisone by Dr. Edward C. Kendall and Tadeusz Reichstein, and 6-
mercaptopurine by Doctors George H. Hitchings and Gertrude B. Elion. These scientists
received the Nobel Prize in Physiology or Medicine for their achievements.
Keywords: Aminopterin, methotrexate, cortisone, 6-mercaptopurine.
