A chemistry set in Birmingham
John Robert Vane was born on March 29, 1927, in Tardebigge, Worcestershire, the youngest of three children. His father, Maurice Vane, was the son of Jewish immigrants from Russia and ran a small company making portable buildings; his mother, Frances, came from a Worcestershire farming family. John grew up in a suburb of Birmingham, went to the local state school from the age of five and then to King Edward VI High School in Edgbaston.
The Second World War coloured his teenage years. His school was evacuated to the countryside, then returned to Birmingham just as the air raids began, and for four years he spent many nights with his family in the shelter at the bottom of the garden. At twelve his parents gave him a chemistry set for Christmas, and experimenting became his passion. His first laboratory was his mother’s kitchen, until a small explosion involving hydrogen sulphide turned the freshly painted blue walls a dirty green. His father then built him a wooden shed in the garden, fitted with a bench, gas and water, and the experiments expanded.
Anything but chemistry
In 1944 he went to the University of Birmingham to study chemistry, but the practical classes, with nothing unknown except the percentage yield, bored him. He realised that what he loved was experiment, not chemistry. When the professor, Maurice Stacey, asked what he wanted to do after graduating, Vane said anything but chemistry. That very morning Stacey had received a letter from Harold Burn in Oxford asking for a young chemist to train in pharmacology. Vane accepted on the spot and went straight to the library to find out what pharmacology was.
Vane later wrote that if anyone could be said to have moulded pharmacology around the world it was Burn, through his style of research, the clarity of his writing and above all the school of young scientists he trained, which made his Oxford laboratory the main training ground for British pharmacologists. Oxford was also where Vane and his wife made their first home and where both of their daughters were born. In 1953 the pharmacologist Arnold Welch invited him to join the Department of Pharmacology at Yale.
He joined Burn’s department in 1946 with no biological training at all, and caught his teacher’s enthusiasm. Burn, he wrote, taught him the essence of experimentation: never ignore the unusual. After a pharmacology degree and a brief spell at Sheffield, he took a doctorate at Oxford under Geoffrey Dawes, completed in 1953. He then spent two years as an assistant professor at Yale before returning to London in 1955 to the Institute of Basic Medical Sciences at the Royal College of Surgeons, where he stayed for 18 years and became Professor of Experimental Pharmacology.
Watching hormones in real time
At the Royal College of Surgeons Vane developed a technique called cascade superfusion bioassay. Blood or fluid from an organ was dripped over a series of small strips of living tissue, each sensitive to a different hormone, so that the release and destruction of substances in the circulation could be watched moment by moment. It let his group see things no chemical test of the time could.
One of the first things they saw involved the lungs. With the Brazilian pharmacologist Sérgio Ferreira, Vane showed in 1967 that the lungs destroy most of the blood-pressure-lowering hormone bradykinin in a single pass, and his group showed that the lungs also convert angiotensin I into angiotensin II, a powerful hormone that raises blood pressure. Ferreira had found that the venom of a Brazilian pit viper, the jararaca, contains a factor that boosts bradykinin. Using it, Vane’s laboratory showed that the venom also blocks the enzyme that makes angiotensin II, the angiotensin-converting enzyme, or ACE.
From snake venom to blood-pressure pills
Vane saw the medical potential at once. As a consultant to the American drug company Squibb, he suggested in 1967 that its scientists study ACE and search for drugs to block it, and then that they work with Ferreira on the venom peptides. Squibb’s chemists Miguel Ondetti and David Cushman used the venom peptides as a template, and in 1975 they made captopril, the first ACE inhibitor, approved for medical use in 1980. Cushman later credited the first major breakthrough to Vane’s suggestion.
ACE inhibitors such as captopril, enalapril, lisinopril and ramipril became some of the most widely prescribed medicines in the world. They lower blood pressure, help failing hearts work, protect the kidneys of people with diabetes, and improve survival after heart attacks. Vane did not invent the drug, but his laboratory found the target and pointed industry towards it.
How aspirin works
Aspirin had been sold since 1899, and nobody knew how it worked. In the mid-1960s Vane’s group turned to prostaglandins, newly discovered fatty-acid hormones involved in pain, fever and inflammation. Vane suspected that aspirin worked by stopping their production. In 1971 he showed that aspirin and the related drug indomethacin block the enzyme that makes prostaglandins, now known as cyclooxygenase. Overnight, a whole class of medicines, the non-steroidal anti-inflammatory drugs, had an explanation.
The discovery has had enormous practical effects. It explained why these drugs relieve pain and fever and also why they can irritate the stomach. It laid the scientific basis for low-dose aspirin to prevent heart attacks and strokes, by stopping platelets from making a clotting hormone. And it led directly to the development of COX-2 inhibitors, anti-inflammatory drugs designed to spare the stomach, a field Vane himself worked on in later years.
Prostacyclin and drug discovery at Wellcome
In 1973 Vane became director of research and development at the Wellcome Foundation, a drug company owned by a medical charity, taking a core of his academic colleagues with him. Some friends thought he was selling out; he pointed to Henry Dale, who had faced the same doubts seventy years earlier and gone on to great science at Wellcome. In 1976 the prostaglandin group he founded there, led by Salvador Moncada and working with the Polish scientist Ryszard Gryglewski, discovered prostacyclin, a short-lived hormone made by the lining of blood vessels that relaxes them and stops platelets from clumping. A synthetic form, epoprostenol, became a treatment for pulmonary arterial hypertension.
During his years as research director, Wellcome also developed the muscle relaxant atracurium, widely used in anaesthesia, and the epilepsy drug lamotrigine. Vane shared the 1982 Nobel Prize in Physiology or Medicine with Sune Bergström and Bengt Samuelsson for their discoveries about prostaglandins, and he was knighted in 1984.
Founder and mentor
At 59 Vane left Wellcome to found the William Harvey Research Institute at St Bartholomew’s Hospital Medical College in London, which grew into a major centre for cardiovascular and inflammation research with about 130 scientists. He published more than 900 scientific papers. Colleagues described him as shy but sociable, generous and hospitable, with insatiable curiosity and a nose for nonsense; one former student said he taught them how to work, teach, learn and conduct themselves as scientists.
At the William Harvey Research Institute Vane’s own research turned to selective inhibitors of COX-2, the form of the prostaglandin enzyme switched on in inflammation, and to the balance between nitric oxide and endothelin, two substances made by blood vessel walls that open and squeeze them. He retired as full-time director in 1995 and became director of the charitable William Harvey Research Foundation. In 1991, with a colleague, he founded a company, Vanguard, to develop promising compounds that drug companies had shelved for reasons other than safety, an attempt to rescue useful medicines from the commercial scrap heap. Among more than 50 awards, he shared the 1977 Lasker Award with Bergström and Samuelsson, was elected a Fellow of the Royal Society in 1974 and a foreign associate of the US National Academy of Sciences in 1983, and received honorary doctorates in Kraków, Paris, New York and Aberdeen.
He made regular visits to Poland from 1962, often carrying chemicals and equipment, which helped Polish scientists through the isolation of the Cold War; Poland gave him its Order of Merit in 2003. He was also a public defender of the responsible use of animals in medical research and was targeted by animal rights extremists, who firebombed his house.
Jewish heritage
Vane’s Jewish roots came through his father, Maurice, whose parents had emigrated from Russia to England; his mother came from a non-Jewish English farming family. He described his family background plainly in his Nobel autobiography but did not write about religion, and there is no record that he practised Judaism. He is included in lists of Jewish Nobel laureates on the basis of his paternal heritage.
Family and legacy
In 1948 Vane married Elizabeth Daphne Page; they had two daughters, Nicola and Miranda, both born in Oxford. From 1973 the couple spent winters on the Caribbean island of Virgin Gorda, where they built a house and garden. He died of pneumonia on November 19, 2004, at the age of 77, after complications from leg and hip fractures earlier that year. Lady Vane died in 2021.
Few scientists have touched so many medicine cabinets. Every packet of aspirin or ibuprofen comes with an explanation he supplied; every prescription for an ACE inhibitor traces back to experiments in his laboratory with snake venom and lungs; and the daily low-dose aspirin taken by millions of people to protect their hearts rests on the chemistry he uncovered.
Sources & further reading
John R. Vane, Biographical, NobelPrize.org · Caroline Richmond, Sir John Vane (obituary), BMJ 2004 · David Cushman, Lasker Award essay on the discovery of captopril, Lasker Foundation · Captopril, Wikipedia · John Vane, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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