a dramatic reduction in the patient's tumor masses. Although the effect lasted only a few weeks, and the patient had to return for another set of treatment, that was the first step to the realization that cancer could be treated by pharmacological agents. The patient ultimately died of cancer on December 1, 1942, 96 days after his first dose. Publication of the first clinical trials was reported in 1946 in The New York Times. Antifolates Shortly after World War II, a second approach to drug therapy of cancer began. Sidney Farber, a pathologist at Harvard Medical School, studied the effects of folic acid on leukemia patients. Folic acid, a vitamin crucial for DNA metabolism (the significance of DNA was not known at that time), had been discovered by Lucy Wills, when she was working in India, in 1937. It seemed to stimulate the proliferation of acute lymphoblastic leukemia (ALL) cells when administered to children with this cancer. In one of the first examples of rational drug design (rather than accidental discovery), Farber used folate analogues synthesized by Harriett Kiltie and Yellapragada Subbarow of Lederle Laboratories. These analogues — first aminopterin and then amethopterin (now methotrexate) were antagonistic to folic acid, and blocked the function of folate-requiring enzymes. When administered to children with ALL in 1948, these agents became the first drugs to induce remission in children with ALL. Remissions were brief, but the principle was clear — antifolates could suppress proliferation of malignant cells, and could thereby re-establish normal bone-marrow function. Farber met resistance to conducting his studies at a time when the commonly held medical belief was that leukemia was incurable, and that the children should be allowed to die in peace. Afterwards, Farber's 1948 report in the New England Journal of Medicine was met with incredulity and ridicule. In 1947, Major League Baseball Hall of Famer Babe Ruth, who was battling nasopharyngeal cancer, became one of the first human subjects of pteroyl triglutamate (also known by its brand name Teropterin, and similar to aminopterin) treatment. Dr. Richard Lewisohn of Mount Sinai Hospital in New York administered the drug, and over the course of several months, Ruth's condition began to improve. However, Ruth died the following year. In 1951, Jane C. Wright demonstrated the use of methotrexate in solid tumors, showing remission in breast cancer. Wright's group was the first to demonstrate use of the drug in solid tumors,