Vane and how aspirin works

Aspirin tablets went on sale in 1900 and were used for decades against fever, pain and inflammation with no agreed idea of how they worked. In the test tube aspirin inhibited many enzymes, but only at high concentrations, so none of those effects could be tied to its anti-inflammatory, fever-lowering or pain-relieving action.

John Vane, a pharmacologist at the Institute of Basic Medical Sciences of the Royal College of Surgeons of England in London, measured hormones with a cascade bioassay, in which blood or perfusion fluid flowed over strips of animal tissue that contracted or relaxed in response. With Priscilla Piper he had found an unstable substance released from guinea pig lungs during anaphylaxis, rabbit aorta contracting substance, whose release aspirin blocked. Around 1970, in anesthetized dogs that were overventilated, he saw that an infusion of aspirin lessened the fall in blood pressure and strongly inhibited the release of prostaglandins from the lungs.

Over a weekend he formed the idea that aspirin stopped prostaglandins being made. On the Monday he told Sergio Ferreira and Piper that he thought he knew how aspirin worked. Using a method described by Änggård and Samuelsson, he homogenized guinea pig lungs, spun off the cell debris, added arachidonic acid to the fluid in test tubes, and measured the prostaglandins formed. By evening he was convinced that aspirin and indomethacin, but not morphine, strongly inhibited their formation. Ferreira and Moncada found the same in the spleen, and Smith and Willis, working independently, in platelets. All three studies were published together in 1971.

Vane proposed that this block was the basis of the drugs' therapeutic action, and it accounted for their side effects too. The enzyme involved is the cyclooxygenase, or COX. Later work showed that aspirin permanently acetylates COX in platelets and stops them making thromboxane A2, which explains its antithrombotic effect; 75 to 100 mg a day is enough.

Vane moved in 1973 to the Wellcome Foundation as director of research and development, and in 1976 his group discovered prostacyclin. He shared the 1982 Nobel Prize in Physiology or Medicine with Sune Bergström and Bengt Samuelsson for their discoveries concerning prostaglandins.