Observations of unprecedented remissions following novel treatment for acute leukemia in children in 1948

Half a century ago, a diagnosis of leukemia in a child was considered a death sentence. Today, approximately 85% of children diagnosed with this once fatal disease are cured.1,2 The discovery that ushered in this dramatically transformed outlook was the observation by Sidney Farber (1903–1973) and his colleagues in Boston in 1948 that drugs that acted against the vitamin folic acid could produce remissions in children with acute leukemia.3 While carefully controlled studies were required to develop therapeutic regimens developed from these initial observations,4,5 the Farber article is featured in the James Lind Library because it is an example of a treatment effect that is so dramatic that bias can be confidently ruled out as an explanation for the observations.6 What led to the landmark findings in 1948, and what evidence was published subsequently confirming that a major advance in treatment had been discovered?