THE pharmacologist John Vane shared the Nobel Prize for Medicine in 1982 for solving one of medical science’s most baffling mysteries: how aspirin worked. The Ancient Egyptians, the Greeks and the Romans had all used willow bark to treat pain; it contains salicylates, from which aspirin is chemically derived. In the 19th century, the drug became known for its painkilling and anti-inflammatory effects, and in 1948 the prescient Californian Dr Lawrence Craven recommended that his patients take an aspirin a day to reduce the risk of heart attack. But not until Vane’s discovery could anyone work out how this versatile and mysterious drug actually operated.

Vane had already developed a system that allowed him to measure, almost instantaneously, the level of a number of hormones in blood at the same time. Using this, he was able to determine that aspirin inhibits the action of prostaglandins — compounds like hormones that cause inflammation, pain and fever in the body. He also worked out that even a tiny dose of aspirin stops the production in platelets of a prostaglandin called thromboxane, which causes platelets to stick together to plug any ruptures in blood vessels. This provided scientific justification for aspirin’s efficacy in preventing blood clots, a common cause of heart attacks and strokes.

Though it was his work on aspirin that won him the Nobel prize, Vane made many other advances in the field of pharmacology over his long and distinguished career. Many of the current remedies for hypertension, for example, owe their foundation to his discoveries; and as the director of the Wellcome Foundation he oversaw the development of drugs to combat such diverse ills as viral infection, gout and epilepsy. The drugs he was directly or indirectly responsible for producing are now some of the most frequently used treatments in medicine.

John Robert Vane became a pharmacologist by accident. His first choice of career, stemming from a childhood hobby, was chemistry, and he graduated in that subject from the University of Birmingham in 1946. As an experimentalist by nature, however, he did not find chemistry as rewarding as he had imagined. Discussing his future with his head of department, he was told that J. H. Burn in Oxford was seeking graduates to be trained in pharmacology, the study of drug action.

“Without hesitation,” he later wrote, “I grasped the opportunity. I immediately went to the library to find out what pharmacology was all about.” It turned out to be exactly what he was looking for, and he never forgot Burn’s inspirational early influence on his work and thinking.

After qualifying, he spent a short time at Sheffield University before returning to postgraduate studies in Oxford. After receiving his DPhil he went to join the Department of Pharmacology at Yale as an assistant professor. The roots of much of Vane’s subsequent work could be traced back to his Oxford days and to the friendships he forged while there.

In 1955 he returned to the UK and embarked upon what might be regarded as the first of his three major creative periods. He joined W. D. M. Paton’s department of pharmacology at the Institute of Basic Medical Sciences, eventually located at the Royal College of Surgeons in London.

Paton was succeeded as head of department in 1961 by G. V. R. Born, a friend of Vane’s from Oxford. Vane rose quickly through the academic ranks, gaining a chair in 1966. Under his and Born’s guidance, the department provided a productive intellectual environment which not only nurtured important breakthroughs but also kick-started the careers of many of today’s most able pharmacologists.

It was during these years that Vane perfected his signature bioassay system, which enabled him to measure with astonishing rapidity and specificity the levels of many blood hormones simultaneously by measuring the contraction of small strips of muscle taken from tissues known to be especially sensitive to those hormones. This approach suited his temperament, for insights and ideas came quickly to him and he was impatient to confirm them.

During his time there he made two hugely important contributions to his subject. Working with S. H. Ferreira, Y. S. Bakhle and others, he laid down the experimental evidence which persuaded him that inhibition of the hormone angiotensin would be a useful therapy for hypertension. At the time he consulted for the pharmaceutical company Squibb in the US; Welch, a friend from his time at Yale, was the organisation’s research director. Welch backed Vane’s idea; the ultimate result was the development of the angiotensin-converting enzyme inhibitors, a class of drugs which revolutionised the treatment of hypertension.

In 1971 Vane began his work on aspirin. Over a weekend he conceived the notion that the mysterious drug might work by inhibiting the generation of prostaglandins. He turned again to his bioassay system for the answer and within a few days he had convinced himself and his colleagues that this indeed was the missing mechanism of action.

This concept, which he further expanded mainly with Ferreira, S. Moncada and R. J. Flower, provided the key to understanding the action of many other anti-inflammatories. It also influenced the development of future anti-inflammatories — including the Cox-2 inhibitors, which have fewer gastric side-effects than aspirin.

In 1973 there was a change in Vane’s circumstances. His colleague Born had left the department to go to Cambridge, and Vane was offered the position of group research and development director of what was then the Wellcome Foundation, a pharmaceutical company whose profits were gifted to the charitable Wellcome Trust. Perhaps he was encouraged to accept this post by the thought that Sir Henry Dale, one of his intellectual heroes, had been crucial to the early development of the company.