Quote · The Peter Attia Drive
#401 ‒ How curiosity transforms medicine: extraordinary discoveries that changed modern healthcare
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The discovery of statins: how fungi provided the blueprint for cholesterol-lowering drugs
At 16:15 · chapter starts 15:15
By the late 1960s, the biochemistry of cholesterol synthesis was well understood, and every medicinal chemist in the field knew that inhibiting HMG-CoA reductase — the rate-limiting enzyme — should lower cholesterol. But nobody knew how to design such an inhibitor from scratch. Akira Endo at Sankyo in Tokyo took a different approach: instead of asking how to design an inhibitor, he asked who in nature had already designed one. [1] — Peter Attia "6,000+ microbial strains screened for statins: Akira Endo and Masao Kuroda screened more than 6,000 microbial strains over two years before…" 17:20 His reasoning was elegant. Fungi have been in chemical competition with bacteria for hundreds of millions of years. Many bacteria need sterols to build their cell membranes, so a fungus that could block bacterial sterol synthesis would have a lethal weapon. Penicillin was one such fungal weapon. An HMG-CoA reductase inhibitor could be another. Endo and his colleague Masao Kuroda screened over 6,000 microbial strains over two years before a strain of Penicillium citrinum from a Kyoto grain shop produced the hit they were looking for, in March 1972. Merck, working independently on a related compound from Aspergillus terreus, obtained FDA approval for lovastatin in 1987. [2] — Peter Attia "Lovastatin FDA approved 1987: Lovastatin, isolated by Merck from Aspergillus terreus and derived from Endo's original fungal finding, recei…" 18:10 From there came simvastatin, atorvastatin, rosuvastatin — the entire statin class that, by any reasonable estimate, has prevented millions of cardiovascular events and premature deaths. Peter notes that this is the cleanest example of a directed search for a natural solution: Endo had a hypothesis about where nature had already solved the problem, and he turned out to be right.
Akira Endo and Masao Kuroda screened more than 6,000 microbial strains over two years before finding the first fungal inhibitor of HMG-CoA reductase that led to statins.
Lovastatin, isolated by Merck from Aspergillus terreus and derived from Endo's original fungal finding, received FDA approval in 1987 as the first commercial statin.
The causal chain from a Brazilian pit viper to captopril spans 70 years and five researchers across three continents, none of whom set out to develop a blood pressure drug. Each step answered only the question in front of it — and each answer unlocked the next.
