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, as opposed to leukemias, which are cancers of the marrow. Several years later at the National Cancer Institute, Roy Hertz and Min Chiu Li then demonstrated complete remission in women with choriocarcinoma and chorioadenoma in 1956, discovering that methotrexate alone could cure choriocarcinoma (1958), a germ-cell malignancy that originates in trophoblastic cells of the placenta.  In 1960 Wright et al. produced remissions in mycosis fungoides.