The Epic Tale of Cholesterol and Statins: A Century of Breakthroughs
Few medical stories rival the century-long quest to decode cholesterol and create statins—drugs that have saved millions of lives. This is a saga of grit, luck, and a quiet genius who changed the world. Let’s dive in.
Cholesterol’s Origins
Our journey starts in 1784, when French physician François Poulletier de La Salle fished cholesterol out of gallstones. Fast-forward to the 19th century, and Michel Eugène Chevreul gave it a name: cholesterine, from the Greek for "bile" and "solid." By the 1920s, chemists Heinrich Wieland and Adolf Windaus cracked its molecular code, snagging Nobel Prizes in 1927 and 1928.
In 1913, Russian pathologist Nikolai Anitschkow made waves by feeding rabbits pure cholesterol, triggering atherosclerosis—the first hint that cholesterol clogged arteries. Skeptics scoffed, but the 1950s Framingham Heart Study sealed the deal: high cholesterol, smoking, and hypertension were a heart attack trifecta.
The Race to Tame Cholesterol
By the 1960s, scientists mapped cholesterol’s 30-step creation process, spotlighting HMG-CoA reductase as the key player. Nobel laureates Konrad Bloch and Feodor Lynen lit the path in 1964, paving the way for a drug breakthrough.
Early tries flopped. MER/29 tanked due to toxicity in 1959. Niacin and fibrates helped a bit, but bile-acid resins were a gastrointestinal nightmare. Hope was fading—until a Japanese scientist turned to an unlikely ally: fungi.
Akira Endo: The Fungus Whisperer
Enter Akira Endo, a man inspired by penicillin’s fungal origins. In 1973, after sifting through 6,000 fungal extracts, Endo struck gold with compactin (mevastatin) from Penicillium citrinum. This molecule slammed the brakes on HMG-CoA reductase, slashing cholesterol in animals.
Success didn’t come easy. Compactin flopped in mice, and Sankyo Co., Endo’s employer, pulled the plug after high-dose dog trials hinted at lymphomas. Undeterred, Endo borrowed chickens from a nearby lab—yes, chickens—and proved his point. By 1978, human cell studies with U.S. collaborators Michael Brown and Joseph Goldstein confirmed compactin’s power.
Statins Hit the Big Time
Sankyo ditched compactin, but Merck & Co. picked up the baton, unveiling lovastatin from another fungus in 1979. Early trials hit safety snags, but the evidence was undeniable. In 1987, lovastatin became the first FDA-approved statin, transforming heart disease treatment.
Brown and Goldstein won a Nobel Prize in 1985 for their LDL receptor work, but Endo? He received zero from Statins’ $25 billion yearly haul. Sankyo even erased him from their history. Late recognition came in 2008 with the Lasker Award—a long-overdue nod.
A Quiet Hero’s Lasting Echo
Picture this: Endo’s doctor prescribes him statins for his own high cholesterol. He smiles—a poignant twist for the man who birthed them. Dr. Endo passed away on June 5, 2024, at 90, leaving a legacy bigger than any award. Today, statins are a global lifeline. As Brown and Goldstein put it: “The millions whose lives are extended through statin therapy owe it all to Akira Endo.”