Snapshot · The Peter Attia Drive
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.
Where this was said
At 17:20 · 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.
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.
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Barry Schwartz's research found that maximizers — people who try to optimize every decision — tend to achieve objectively better outcomes but report lower happiness than satisficers who choose 'good enough.'
Research consistently shows that while people may initially regret poor decisions, in the long run they regret the decisions they didn't make — inaction — far more than the ones they took.
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Harvard psychologist Dan Gilbert, who previously didn't believe in marriage, immediately proposed to his long-term girlfriend after his own research showed that constraints increase satisfaction with choices.
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Only about 3% of FDA-approved drugs have genuinely unclear mechanisms of action, making an unknown mechanism a meaningful early red flag for any compound.
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