Akira Endo, Biochemist Who Found a Way to Fight Heart Disease, Dies at 90
Endo’s research paved the way for the development of drugs to treat high cholesterol and reduce the risk of heart attacks or strokes
Akira Endo, a Japanese biochemist whose research enabled the development of treatments to lower cholesterol, died on June 5 at 90 years old.
A statement from the Tokyo University of Agriculture and Technology, where Endo was a professor emeritus, confirmed his death but did not give a cause, according to the New York Times’ Hisako Ueno and Mike Ives.
High cholesterol raises the risk for heart attacks and strokes. An estimated 17.9 million people die worldwide from heart disease each year, and more than four in five of these deaths are due to stroke or heart attacks. In the 1970s, Endo discovered a class of molecules called statins, which can lower cholesterol by blocking an enzyme that plays a role in its production in the liver.
Statins “have absolutely transformed the prevention of heart disease and stroke,” Bryan Williams, chief scientific and medical officer at the British Heart Foundation, tells BBC News’ Michelle Roberts. “There’s very few treatments in medicine that have happened in the past few years that have had such a dramatic impact.”
Akira Endo was born in 1933 into a rural farming family in northern Japan’s Akita prefecture. His grandfather, who was interested in medicine, inspired in Endo a fascination with mushrooms and other molds. “At the age of 10, I dreamt of becoming a scientist,” Endo wrote in a 2010 journal article.
After graduating from high school, he enrolled in Tohoku University’s College of Agriculture, where he read the autobiography of Alexander Fleming, who discovered penicillin in mold, catalyzing the development of antibiotics. Endo decided that he, too, wanted to study how to make use of molds.
He joined the pharmaceutical company Sankyo after college, looking for mold and fungi that could be used in food processing. From 1966 to 1968, he studied at the Albert Einstein College of Medicine in New York City, where he learned about the connection between high cholesterol and heart disease.
“I often saw ambulances going to take an elderly person who had suffered a heart attack to the hospital,” Endo wrote in his 2010 essay.
At the time, there were limited treatments available for high cholesterol. Some had only mild effectiveness, while others caused significant side effects. Endo decided he wanted to develop a therapeutic drug that would reduce the amount of cholesterol produced in the body.
The presence of too much low-density lipoprotein, or LDL cholesterol, in the blood raises the risk for heart attack and stroke by contributing to plaque buildup in arteries. Endo hypothesized that by blocking the action of an enzyme that helps form cholesterol, he could reduce cholesterol levels in the body.
After returning to Sankyo in Japan, he studied 6,000 different fungal strains in search of one containing a substance that could complete the task. Eventually, in the summer of 1972, he found such a compound: the blue mold penicillium, which formed on rice produced in Kyoto. One strain, later named compactin or mevastatin, showed effectiveness at reducing cholesterol levels in chickens, dogs and monkeys.
Sankyo started clinical trials of compactin, but these were stopped in 1980, because the drug may have caused lymphoma in dogs. The dosage used in the trial, however, was higher than what would have likely been clinically administered.
In 1976, the company Merck in the United States obtained compactin samples and experimental data from Sankyo. Merck eventually developed a different statin, called lovastatin, and began clinical trials in 1980. It received U.S. Food and Drug Administration approval to become the first commercially available statin in 1987.
“Statins … have made a major impact to the prevention and treatment of cardiovascular disease, thereby extending the lives of millions of people across the world,” cardiologists Adrian Chester and Ahmed El Guindy wrote in a 2021 article in Global Cardiology Science and Practice.
“Amazingly, the man who began the process of working out how to deal with the problem of cholesterol—and provided a treatment that benefited and saved the lives of many, many millions of people—never got the [Nobel] prize,” Williams tells BBC News. “I think that’s a shame.”
“In my opinion, this is the second-most important discovery of the century after penicillin,” Joseph Wu, a cardiologist and president of the American Heart Association, tells the Washington Post’s Brian Murphy. “It is the cornerstone of cardiovascular medicine.”