Sidney Farber (1903–1973)
Methotrexate and the very closely related drug aminopterin occupy a significant place in the history of cancer chemotherapy: They were the first drugs found to cause a remission in leukemia and cure a solid tumor. During the 1930s and early 1940s, scientists observed that folic acid–rich foods stimulated the growth and development of bone marrow, the site of blood-cell production. This benefited anemia patients but worsened leukemia in children. For these children, their prognosis was the same in 1940 as it was when the disease was first identified in 1845: Once diagnosed with leukemia, their life expectancy was measured in weeks.
FIRST HOPES IN CHILDHOOD CANCER TREATMENT. Sidney Farber was a Harvard Medical School pediatric pathologist. He hypothesized that if folic acid stimulated the bone marrow, administering a drug that blocked folic acid would depress the bone marrow and shut down excessive production of white blood cells in leukemia. Farber contacted Lederle Laboratories, a company then interested in folic acid, and requested that they develop a chemical that could antagonize folic acid. In 1947, Farber found that the first of these anti-folate compounds, aminopterin, completely—but only temporarily—improved the condition of ten of sixteen children with acute lymphoblastic leukemia. Amethopterin was the first drug effective against non-solid tumors—cancers that are widespread in the body and that cannot be removed surgically.
Methotrexate, a far safer, close chemical derivative of aminopterin, is currently in use. In 1958, methotrexate was shown to cure choriocarcinoma, a malignant solid tumor of the uterus. It is also used for a wide range of rapidly growing cancers, as well as psoriasis and rheumatoid arthritis as a disease-modifying anti-rheumatic drug (DMARD).
Farber was advised early on that children with leukemia should be left to die in peace. His hunches about anti-folate compounds were vindicated, and he is now regarded as the “father of modern cancer chemotherapy.”
SEE ALSO Enbrel, Remicade, and Humira (1998), Gleevic/Glivec (2001).
Sidney Farber, “the father of modern cancer chemotherapy,” founded the Children’s Hospital Center Research Foundation, which expanded the scope of its patient population and became the Dana-Farber Cancer Institute in 1947, a renowned comprehensive cancer treatment and research center.