
Dr Jonathan Tobert, University of Oxford, UK, recalls the landmark statin research by Dr Akira Endo that has saved countless lives.
Akira Endo, the Japanese scientist universally recognised as the discoverer of statins, died on June 5 at the age of 90. The medical importance of his discovery is arguably comparable with Fleming’s discovery of penicillin.1 Endo’s childhood walks to find mushrooms fuelled his lifelong interest in fungi and, in the 1970s, he was searching for agents with useful antimicrobial activity. In 1976, he identified compactin, a potent inhibitor of HMG-CoA reductase, in a fermentation broth of penicillium citrinum.2 Endo quickly appreciated that compactin, an agent inhibiting the rate-limiting step in the cholesterol biosynthesis pathway, might lower plasma lipids.
In collaboration with Hiroshi Mabuchi, Sankyo and others, Endo was involved with studies of the ability of compactin to reduce LDL-C in patients with familial hypercholesterolaemia, and substantial lipid-lowering efficacy was shown. Researchers in other pharmaceutical companies followed up Endo’s research including at Merck Research Laboratories where a compound that became lovastatin was discovered, and then a semisynthetic derivative of lovastatin named simvastatin. The rest is history!
Statins have saved countless lives and Endo was honoured with several well-deserved awards, notably the Lasker-DeBakey Prize in 2008.
Many believe he deserved the Nobel Prize.
For a fuller version of this fascinating story and the major contribution of Akira Endo to the statin era, go to https://www.pcsk9forum.org/remembering-akira-endo-and-the-beginning-of-the-statin-era/
Jonathan Tobert MD PhD is a clinical pharmacologist and trialist. He led the early clinical trials with lovastatin, the first marketed statin, at Merck, and has devoted most of his career to the safety and efficacy of statins. After retiring from Merck, he became an Academic Visitor at the Nuffield Department of Population Health, University of Oxford, UK. He has published several papers on statin adverse effects, including the role of the nocebo effect in statin intolerance.
References
- Thompson GR. Resolving the cholesterol controversy: the scientists who proved the lipid hypothesis of causation of atherosclerosis and coronary heart disease. London: World Scientific Publishing Europe; 2023
- Endo A. A historical perspective on the discovery of statins. Proceedings of the Japan Academy, Series B. 2010;86(5):484-9