Guest editorial – Lawrence J. Marnett, Ph.D. pg. 2
In the mid-1960s, John Vane was a British pharmacologist studying the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin. He was particularly interested in the effect of NSAIDs on the production of prostaglandins.
Prostaglandins were first discovered in 1930 as muscle-contracting components of human semen by the American gynecologists, Ralph Kurzrok and Charles Lieb. Nearly 30 years later, the structures of prostaglandins were elucidated by the Swedish biochemists, Sune Bergstrom and Bengt Samuelsson, and it was discovered that prostaglandins are made in many parts of the body including inflamed tissues.
Vane’s discovery provided a rapid test-tube screen for new anti-inflammatory drugs and many began to emerge from pharmaceutical companies. Although they were more potent than aspirin, their safety wasn’t much better. All NSAIDs cause stomach toxicity in a significant fraction of people who take them. This is due to their ability to reduce prostaglandin production by inhibiting the enzyme, cyclooxygenase, abbreviated COX.
Since the mechanism of their anti-inflammatory activity and their gastrointestinal toxicity is the same, there didn’t appear to be much one could do to reduce NSAID side effects. But Philip Needleman and Michael Holtzman from Washington University provided evidence for the existence of a second COX enzyme, and in 1991, Dan Simmons at Harvard and Harvey Herschman at UCLA simultaneously identified the new gene—COX-2.