Cyclooxygenase: Past, present and future. A tribute to John R. Vane (1927–2004)

Study of the prostaglandins led directly to the elucidation of the mode of action of aspirin which inhibits their synthesis. John Vane elegantly demonstrated in 1971 that non-steroid anti-inflammatory drugs (NSAIDs) blocked cyclooxygenase (COX), the enzyme which makes prostaglandins. In 1991, Daniel Simmons described the gene which expresses a second cyclooxygenase, COX-2. This discovery explained the anti-inflammatory actions of NSAIDs, inhibition of COX-2, and their side actions, inhibition of COX-1. Within 8 years selective COX-2 inhibitors became available for the treatment of inflammation without the disadvantage of gastric toxicity. Recently, a COX-1 variant protein, named COX-3, sensitive to inhibition with acetaminophen, was characterised, cloned and expressed.