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. 6-MP Joseph Burchenal, at Memorial Sloan-Kettering Cancer Center in New York, with Farber's help, started his own methotrexate study and found the same effects. He then decided to try to develop anti-metabolites in the same way as Farber, by making small changes in a metabolite needed by a cell to divide. With the help of George Hitchings and Gertrude Elion, two pharmaceutical chemists who were working at the Burroughs Wellcome Co. in Tuckahoe, many purine analogues were tested, culminating in the discovery of 6-mercaptopurine (6-MP), which was subsequently shown to be a highly active antileukemic drug. Vinca Alkaloids The Eli Lilly natural products group found that alkaloids of the Madagascar periwinkle (Vinca rosea), originally discovered in a screen for anti-diabetic drugs, blocked proliferation of tumour cells. The antitumour effect of the vinca alkaloids (e.g. vincristine) was later shown to be due to their ability to inhibit microtubule polymerization alkaloys, and therefore cell division. National Cancer Chemotherapy Service Center The NCI, headed by Dr. John R. Heller Jr., lobbied the United States Congress for financial support for second-generation chemotherapy research. In response, Congress created a National Cancer Chemotherapy Service Center (NCCSC) at the NCI in 1955. This was the first federal programme to promote drug discovery for cancer – unlike now, most pharmaceutical companies were not yet interested in developing anticancer drugs. The NCCSC developed the methodologies and crucial tools (like cell lines and animal models) for chemotherapeutic development. Combination chemotherapy In 1965, a major breakthrough in cancer therapy occurred. James F. Holland, Emil Freireich, and Emil Frei hypothesized that cancer chemotherapy should follow the strategy of antibiotic therapy for tuberculosis with combinations of drugs, each with a different mechanism of action. Cancer cells could conceivably mutate to become resistant to a single agent, but by using different drugs concurrently it would be more difficult for the tumor to develop resistance to the combination. Holland, Freireich, and Frei simultaneously administered methotrexate (an antifolate), vincristine (a Vinca alkaloid), 6-mercaptopurine (6-MP) and prednisone — together referred to as