Dr Jonathan Tobert, University of Oxford, UK, recalls the landmark statin research by Dr Akira Endo that has saved countless lives.
The discovery of statins by Japanese scientist, Akira Endo, who died on June 5 at the age of 90 has helped prevent countless unnecessary deaths in the 35 years since the start of the ‘statin era’. The medical importance of Endo’s discovery is arguably comparable with Fleming’s discovery of penicillin.1
In 1976, Endo identified compactin, a potent inhibitor of HMG-CoA reductase, in a fermentation broth of penicillium citrinum,2 and quickly appreciated that compactin, which inhibited the rate-limiting step in the cholesterol biosynthesis pathway, might lower plasma lipids. Endo was subsequently involved with studies which showed substantial lipid-lowering efficacy of compactin in patients with familial hypercholesterolaemia. At about the same time, Al Alberts and colleagues at Merck Research Laboratories discovered a potent HMG-CoA reductase inhibitor in a fermentation broth of aspergillus terreus which later became lovastatin.
Sankyo subsequently developed pravastatin and other statins followed, most importantly atorvastatin, which today is the most widely prescribed statin.
Akira 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):484-93
