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FEATURE ARTICLE

Statins: From Fungus to Pharma

The curiosity of biochemists, mixed with some obvious economic incentives, created a family of powerful cardiovascular drugs

Philip A. Rea

Click to Enlarge ImageIn 1966, Akira Endo, a young Japanese biochemist, started an adventure that would ultimately save thousands, if not millions, of lives. Only 33 years old at the time, Endo was a research scientist at Sankyo—a pharmaceutical company, later known as Daiichi Sankyo, in Tokyo—where he was looking for enzymes in fungal extracts for improving the quality of certain foodstuffs. But his research was soon to enter a new realm. As he would write years later: "In the mid-1960s, fascinated by several excellent reviews on cholesterol biosynthesis by Konrad Bloch of Harvard University, who received the Nobel Prize in 1964, I became interested in the biochemistry of cholesterol and other lipids." Endo's curiosity triggered research that eventually spawned one of today's most widely used families of drugs.

Born in 1933 on a farm in northern Japan, Endo became intrigued by mushrooms as a child. He most admired Alexander Fleming's famous work on fungi, which ultimately led to the development of penicillin. Even into adulthood, Endo remained interested in fungi and how they could be used. It was at Sankyo, by screening more than 200 fungal species, that he was able to identify enzymes capable of decreasing the pulp in fruit juices.

Endo's research, however, turned to bigger things when he took a two-year leave of absence from Sankyo to work at Albert Einstein College of Medicine in New York City. There, he entered the world-renowned biochemistry laboratory of Bernard L. Horecker and met Lawrence I. Rothfield, who is now a professor of microbiology at the University of Connecticut Health Center. Endo learned from Rothfield—who had been a physician at New York University Hospital for more than 10 years before joining Albert Einstein College of Medicine—that high blood cholesterol poses a major risk for cardiovascular disease.

As we shall see, Endo's two interests—fungi and cholesterol—merged and spurred the discovery and development of a group of cholesterol-lowering drugs called statins. The number of deaths from cardiovascular diseases has decreased by about 25 percent in the United States since 1994, not because of a radical change in lifestyle—though this is happening—but because of the ready availability of cardioprotective drugs. Of the handful of drugs out there that have fought cardiovascular diseases, statins are right at the top of the list.






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