John Vane pointed the way to ACE inhibitors

Person: John Vane
Lived: 1927–2004
Field: Pharmacology
From: British

The story

In the 1960s John Vane, a pharmacologist at the Royal College of Surgeons in London, was using a technique his group had built to watch hormones in the bloodstream appear and vanish. One of the things it revealed was that the lungs play a large part in controlling blood pressure. With the visiting Brazilian scientist Sérgio Ferreira, Vane showed in 1967 that the lungs destroy most of the blood-pressure-lowering hormone bradykinin in a single pass, and with his colleague K. K. F. Ng he showed that the lungs also convert angiotensin I into angiotensin II, one of the most powerful blood-pressure-raising hormones known.

Ferreira had found that the venom of the jararaca, a Brazilian pit viper whose bite makes victims’ blood pressure collapse, contains a factor that strengthens bradykinin. Work in Vane’s laboratory showed that the venom peptides also block the enzyme that makes angiotensin II, the angiotensin-converting enzyme, or ACE. Vane, who had a Jewish father descended from Russian immigrants, saw a possible medicine.

He was a consultant to the American company Squibb. According to the Squibb biochemist David Cushman, it was Vane who suggested in 1967 that someone at the company study ACE and look for inhibitors, and the first major breakthrough came when Vane suggested collaborating with Ferreira on the venom. Cushman and the chemist Miguel Ondetti used the venom peptides as a model for the shape of the enzyme’s active site and in 1975 designed captopril, a small molecule that could be taken as a pill. It was approved for medical use in 1980.

Captopril was the first of a family of drugs, including enalapril, lisinopril and ramipril, that became some of the most prescribed medicines in the world. ACE inhibitors lower blood pressure, ease the strain on failing hearts and help protect the kidneys of people with diabetes. Vane did not make the drug himself, but the target, the clue from the snake and the push to industry all came from his laboratory.

Why it matters

ACE inhibitors, which grew from Vane’s research and advice, are taken every day by millions of people to control blood pressure and protect their hearts and kidneys.

About John Vane

British pharmacologist who discovered how aspirin works, found prostacyclin and helped launch ACE inhibitors, among the world’s most used heart and blood-pressure medicines.

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John Vane

1927–2004 · Pharmacology

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