The First Time a Drug Pushed Back Childhood Leukemia

In 1947, Sidney Farber was a pediatric pathologist at Boston Children's Hospital who had just done a careful and discouraging experiment. He had given children with acute lymphoblastic leukemia supplemental folic acid, on the reasonable theory that the bone marrow looked depleted of B-vitamins. The leukemias did not get better. They got dramatically worse. Folate, in those marrow cells, was fuel.

The right move, he decided, was to do the opposite. He wrote to Yellapragada SubbaRow at Lederle Laboratories — the chemist who had worked out folate's structure — and asked for an antifolate, a molecule that looked like folic acid enough to fool the cell but blocked the enzyme that used it. SubbaRow's team made one. They called it aminopterin.

On December 16, 1947, Farber gave the first dose to a critically ill 8-year-old boy. The child improved. Within weeks, his blood counts looked normal. The leukemic cells receded from his bone marrow. The remission did not last — none of them did, in those early trials — but it was the first time anyone had pushed back this disease with a drug.

Farber treated 16 children. Ten responded. He published in the New England Journal of Medicine on June 3, 1948, in deliberately cautious language; the paper is titled "Temporary Remissions in Acute Leukemia in Children." Reviewers were skeptical. The remissions were short. The children all eventually relapsed and died.

What survived was the principle: a synthesised small molecule could selectively poison a cancer. Farber's protégés iterated. Aminopterin gave way to methotrexate, gentler in the same family, still used in pediatric leukemia regimens that now cure roughly 90 percent of cases. The field he had launched picked up a name a few years later: chemotherapy.