In 1946–1947, while studying at Yale, he coauthored with Leon Greenberg a series of three papers on acetanilide, an analgesic that was still in use at the time, aiming to establish why it caused methemoglobinemia. Although more than half a century had passed since acetanilide was first used clinically, there was wide-ranging disagreement concerning its metabolism, and numerous theories had been postulated. The first of these three papers summarized these theories, and reexamined the proportion of various acetanilide metabolites in human urine. Finding that p-aminophenol conjugates were excreted, they refuted the earlier theories that the accumulation of this substance in the body was causing methemoglobinemia.[3] Of far greater impact was the second paper in this series, showing that paracetamol was a metabolite of acetanilide in the blood.[4] The third paper in the series reported that even large amounts of paracetamol (up to 4 grams per kg of body weight) did not produce methemoglobinemia in albino rats.[5] This observation, together with later studies conducted by Bernard Brodie and Julius Axelrod led to the rediscovery of paracetamol as a drug.[6]
