The Immediate Post-World War II Years: Cancer Chemotherapy Spreads its Wings

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.