Scientifically Speaking | Remembering Akira Endo, the scientist who revolutionised heart care - Hindustan Times
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Scientifically Speaking | Remembering Akira Endo, the scientist who revolutionised heart care

ByAnirban Mahapatra
Jun 24, 2024 08:00 AM IST

Endo’s discovery, which came from a mold like the kind that grows on oranges, marked a significant advance in medicine, yet remains relatively unknown

Do you take statins to reduce blood cholesterol like hundreds of millions of others? Then you should know Akira Endo. The Japanese biochemist, who passed away on June 5 at the age of 90, discovered the first statin, a revolutionary cholesterol-lowering drug that reduces the risk of heart attacks. This became the most lucrative class of drugs in history.

This undated photo released by Jiji Press on June 11, 2024 shows professor Akira Endo from the Tokyo University of Agriculture and Technology in Tokyo. Endo, the Japanese biochemist whose pioneering research on fungi led to the development of cholesterol-lowering statins, has died at the age of 90, Japanese media reported on June 11, 2024. (Photo by JIJI Press / AFP) / Japan OUT(AFP) PREMIUM
This undated photo released by Jiji Press on June 11, 2024 shows professor Akira Endo from the Tokyo University of Agriculture and Technology in Tokyo. Endo, the Japanese biochemist whose pioneering research on fungi led to the development of cholesterol-lowering statins, has died at the age of 90, Japanese media reported on June 11, 2024. (Photo by JIJI Press / AFP) / Japan OUT(AFP)

Endo’s discovery, which came from a mold like the kind that grows on oranges, marked a significant advance in medicine, yet remains relatively unknown to the public. Endo — like his idol Sir Alexander Fleming, the discoverer of penicillin — reaped little of the financial rewards.

Endo's fascination with fungi and their potential to give us lifesaving drugs was kindled in his youth. Born on a farm in 1933 in the rural town of Yurihonjo, Japan, he grew up surrounded by nature's wonders and guided by his grandfather's teachings about local fungi. This early exposure set him on a path that would lead to one of the most important medical discoveries of the 20th century.

Inspired by the story of Fleming's serendipitous discovery of penicillin in 1928, Endo pursued a career in biochemistry. He dreamed of uncovering a transformative natural product similar to Fleming's accidental discovery of penicillin.

"For me, Fleming was a hero," Endo said to the Japanese medical publisher Igaku-Shoin in 2014 (as later recalled in Endo’s obituary in The New York Times). "I dreamed of becoming a doctor as a child but realised that even non-doctors can save lives and contribute to society."

After studying agriculture at Tohoku University, Endo joined Sankyo, a pharmaceutical company, in the late 1950s, where his early work involved optimising enzymes for food production.

In the 1960s, Endo earned a doctoral degree in biochemistry from Tohoku University and worked as a research associate at the Albert Einstein College of Medicine in New York City. Although he initially aimed to find a cure for strokes, which had claimed the lives of his father and grandparents, his exposure to the prevalence of heart disease in the US led him to shift focus.

Cholesterol had been identified as a major factor in heart disease, a leading cause of death globally by the 1960s. At that time, existing cholesterol-lowering drugs had major side effects. Companies were searching for a chemical compound that would block the enzyme HMG-CoA reductase (which is critical to cholesterol production in the body) but had found one that worked in living animals.

Based on his expertise in fungi, Endo believed that molds could produce a cholesterol-lowering compound. This idea was inspired by the discovery of penicillin, the first antibiotic, which had been discovered by Fleming in mold.

Over two years, Endo and his team at Sankyo tested 6,000 fungal broths, meticulously brewing and analysing each one. It was an arduous process, filled with late nights and countless disappointments. Yet, Endo's unwavering dedication paid off in 1973 when his team discovered compactin, a potent inhibitor produced by Penicillium citrinum, a mold. Compactin was the first statin.

It wasn’t smooth sailing at first. Initial tests of compactin in rats were unsuccessful, nearly dooming the project. A stroke of luck came when a colleague offered hens for testing, leading to a breakthrough that showed compactin's efficacy in lowering cholesterol.

Unfortunately, Endo faced internal resistance at Sankyo. The company's management was sceptical that statins would work, preferring to invest in established cholesterol drugs. Undeterred, Endo conducted secret clinical trials at Osaka University, which confirmed compactin's effectiveness in humans.

At Osaka University, Akira Yamamoto tested compactin on patients with very high cholesterol. Although the first patient experienced severe muscle pain due to a high dose, subsequent lower doses successfully reduced cholesterol levels.

In a twist of fate, a 1976 agreement between Sankyo and Merck inadvertently helped Merck by granting access to its data and methods. Merck developed its own statin, lovastatin, which hit the market in the United States in 1987 as Mevacor. Sankyo eventually licensed another statin, marketed as Pravachol by Bristol-Myers Squibb in 1991. By the mid-1990s, statins were hailed as a medical miracle, significantly reducing heart attack and stroke risks.

Statins became a blockbuster drug class, with annual sales reaching billions of dollars. These medications, including Pfizer's Lipitor (a statin with a different chemical structure, which became the world's best-selling drug) transformed heart health care and saved many lives.

Yet, despite the monumental impact of his discovery, Endo saw little personal gain. When he left Sankyo in 1978, he was earning a modest salary and never received royalties from the statin that originated in his lab. Nobel laureates Michael S. Brown and Joseph Goldstein, however, credit Endo for extending millions of lives through statin therapy.

Endo’s legacy lives on today. For decades, the pharmaceutical industry has favoured synthetic compounds, often overlooking the complex, evolved molecules found in nature. Endo's work, rooted in the study of molds, reminds us of the immense potential of natural products in medicine. Nature is still the best medicine cabinet.

In his later years, Endo continued to contribute to science, exploring new fungal applications in various products. A 2006 news story in the Wall Street Journal recounts that he faced high cholesterol himself. During a routine health check, a doctor unaware of Endo’s legacy recommended statins. Endo briefly took Mevacor but later lowered his cholesterol through exercise.

When asked why the discoverer of statins did not take statin himself, Endo answered with a Japanese proverb – “The indigo dyer wears white trousers.”

Anirban Mahapatra is a scientist and author, most recently of the popular science book, When The Drugs Don’t Work: The Hidden Pandemic That Could End Medicine. The views expressed are personal.

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