Akira Endo, scientist whose knowledge of fungi led him to discover the first statin – obituary

Endo: he isolated 'mevastatin' from Penicillium citrinum, a blue-green mould sometimes found on old citrus fruit
Endo: he isolated 'mevastatin' from Penicillium citrinum, a blue-green mould sometimes found on old citrus fruit - Alamy

Akira Endo, who has died aged 90, discovered the first statin, a chemical that prevents heart attacks and strokes by reducing the concentration in blood of “bad” cholesterol, helping to prolong the lives of millions of people.

In the early 1970s, when Endo, a biochemist with the Japanese pharmaceutical company Sankyo, began his research, the only way to lower blood LDL (low-density lipoproteins – i.e. “bad”) cholesterol was to combine an unpalatable diet with medications causing unpleasant side-effects.

Scientists knew that blocking an enzyme crucial in the body’s production of cholesterol, HMG-CoA reductase, could be the key to a better drug, but they could not find a substance that would work in living animals.

Endo’s achievement arose out of a lifelong interest in the medicinal properties of fungi. Knowing that bacteria, like humans, need cholesterol to keep their cell walls together, he reasoned that some fungus had probably evolved a substance that would knock out the enzyme as a way of depriving enemy bacteria of cholesterol and killing them.

Working in a laboratory in southern Tokyo, he and three assistants set to work, brewing fungal soups and testing them for their ability to block the enzyme, a supply of which they got from rat livers. Some chemicals blocked it well but were rejected because they were toxic.

After testing 6,000 different concoctions, in August 1973 they tested a promising-looking substance made by Penicillium citrinum, a blue-green mould isolated from the rice of a Kyoto trader similar to the mould that grows on old oranges and lemons.

The trouble was that it barely worked in rats (later research would reveal that rats differ from other animals in how they make cholesterol), but when a colleague suggested he might test it on hens, it proved to be a potent inhibitor of HMG-CoA reductase. Later named mevastatin (or compactin), it is now recognised as the first true statin.

Developing the substance was not the end of Endo’s problems, however. To begin with, the directors of Sankyo were unenthusiastic about the discovery because there was no precedent for it. They preferred to develop refinements of then-existing anti-cholesterol drugs and would not support trials in human guinea pigs.

Refusing to be deterred, Endo embarked on a secret experiment at Osaka University with a doctor who was treating patients who had extremely high cholesterol because of a genetic defect.

The first patient in the world to receive a statin, an 18-year-old woman, was also the first to suffer muscle pain, a side-effect that occasionally occurs with statins. Because she had been given an extremely high dose, she became so weak she was unable to walk, but she recovered after the drug was discontinued. When they tried it on other patients at low doses it reduced their cholesterol by an average of 27 per cent.

Statins have earned billions for the pharmaceutical industry but Endo earned nothing in royalties
Statins have earned billions for the pharmaceutical industry but Endo earned nothing in royalties - The Image Bank/Getty

When Sankyo saw the results it agreed to put mevastatin into formal clinical testing. But Sankyo was not the only company working on statins, because it had inadvertently helped a competitor, Merck.

In 1976, under a confidentiality agreement, Sankyo granted Merck access to its data on Endo’s statin. While Sankyo eventually suspended its own clinical trials, Merck went on to discover a substance in a different fungus, lovastatin, that was structurally almost identical to Endo’s. As Mevacor, it became the first statin to win US Food and Drug Administration approval.

By this time Endo had left the company to take up a university post. As a result, even though statins have brought in billions of dollars to the pharmaceutical industry – the global market for them was worth $15 billion in 2023 – he earned nothing in royalties.

Even as the drugs became famous, Endo remained largely unknown. In 2004, however, when Michael Brown and Joseph Goldstein won the Nobel Prize for their work in cholesterol, they wrote: “The millions of people whose lives will be extended through statin therapy owe it all to Akira Endo.”

Endo remained somewhat sceptical of his own discovery. During a health check in 2004 he was told his cholesterol levels were slightly high, and decided to bring them down by changing his diet and taking more exercise. When asked why he had decided to bypass his own discovery, he quoted a Japanese proverb: “The indigo dyer wears white trousers.”

Akira Endo was born on November 14 1933 on a farm in the north of Japan and became fascinated by fungi as a child, after his grandfather told him about a local variety of poisonous mushroom that kills flies but not people.

He grew up at a time following the discovery of penicillin, when the potential to make new drugs from natural products seemed almost limitless. At Tohuko University, Sendai, he devoured a Japanese translation of a biography of Sir Alexander Fleming, and went on to take a PhD in biochemistry at the same university in 1966.

After leaving university he joined the Tokyo-based pharmaceutical company Sankyo, researching food ingredients. His discovery of a fungus that produces an enzyme which breaks down pectin, making fruit juices less pulpy, proved such a hit that the company allowed him a two-year leave of absence to pursue his interest in cholesterol research at the Albert Einstein College of Medicine in New York.

Endo left Sankyo in 1978 to take up a post as a professor at Tokyo Noko University amid some ill-feeling, complaining that the company had ordered scientists in his lab not to help him carry his boxes of papers out of the building.

Later in his university research Endo discovered yet more fungal by-products, for use in chewing gum, cosmetics and other products. Subsequently he became director of Biopharm Research Laboratories.

As Endo’s contribution to the creation of a whole new class of drugs came to be recognised, he was awarded the 22nd Japan Prize in 2006 and the Lasker Award (known as America’s Nobel Prize) in 2008.

Akira Endo, born November 14 1933, died June 5 2024