BOREALIS: You mean to tell me Dr Fauci did go to college and got degrees in everything he was going to working on. Unlike dear leader Trump. Who dodge the draft and party at all the school he went to. How dare you to tell Dr Fauci knows what the fuck he is talking about. Dear Leader Trump is looking out for all us!!!
Youyou Tu, noted. Artemisinin: Discovery from the Chinese Herbal Garden
Louis H. Miller1,* and Xinzhuan Su1 Author information Copyright and License information Disclaimer The publisher's final edited version of this article is available free at Cell
Tu allowed her drug to be tested on herself to convince others it worked. An extra gutsy effort in the search of a drug to save millions of lives.
Abstract
This year’s Lasker DeBakey Clinical Research Award goes to Youyou Tu for the discovery of artemisinin and its use in the treatment of malaria—a medical advance that has saved millions of lives across the globe, especially in the developing world.
The future benefits of many seminal discoveries in basic biomedical sciences are not always obvious in the short run. But for a handful of others, the impact on human health is immediately clear. Such is the case for the discovery by Youyou Tu and colleagues of artemisinin (also known as Qinghaosu) for treatment of malaria. Artemisinin has been the frontline treatment since the late 1990s and has saved countless lives, especially among the world’s poorest children.
The Promise of Project 523
The story of artemisinin began in the unlikely atmosphere of the Cultural Revolution in China as a government initiative to aid the North Vietnamese in their war with the United States. During the war, malaria caused by chloroquine-resistant Plasmodium falciparum was a major problem that spurred research efforts on both sides of the battlefield. In the US, these efforts culminated in the discovery of mefloquine, a compound that was curative in a single dose against chloroquine-resistant parasites (Trenholme et al.,1975). TheNorthVietnamese, however, lacked a research infrastructure and thus turned to China for help.
Under the instructions of Chairman Mao and Premier Zhou, a meeting was held on May 23, 1967 in Beijing to discuss the problem of drug-resistant malaria parasites. This led to a secret nationwide program called project 523, involving over 500 scientists in ~60 different laboratories and institutes (Zhang et al., 2006). Although the project’s short-term goal was to produce antimalarial drugs that could immediately be used in the battlefield (by 1969 three treatments were established), the project’s long-term goal was to search for new antimalarial drugs by screening synthetic chemicals and by searching recipes and practices of traditional Chinese medicine.
Because this work was considered a military secret, no communication about the research to the outside world was allowed, and in any case, during the tumult of the Cultural Revolution, publication in scientific journals was forbidden. For these reasons, no one outside of project 523 knew about the work. Yet within the project, information flowed freely between the members of the various research groups, and findings were presented at their frequent joint meetings.
Without a publication record, who should be credited with the discovery of artemisinin? The answer to this question was not generally known when we (X.S. and L.H.M.) began, in 2007, to delve into the history of the discovery. Our findings left no doubt that the major credit must go to Youyou Tu, who was a principle investigator at the Institute of Chinese Meteria Medica, China Academy of Chinese Medical Sciences (CACAMS). In January 1969, Professor Tu led a team in screening the literature and recipes of traditional Chinese medicine under project 523. She was chosen to present the work of project 523 for the first time in October 1981 in Beijing to a World Health Organization (WHO) visiting study group on chemotherapy of malaria (Tu, 1981).
From Ancient Recipe to Modern Drug
During their search, Youyou Tu and colleagues investigated more than 2,000 recipes of Chinese traditional herbs, compiling 640 recipes that might have some antimalarial activity. They tested in a rodent malaria model more than 200 recipes with Chinese traditional herbs and 380 extracts from the herbs. Among the promising results, extracts from Artemisia annua L. (Qinghao), a type of wormwood native to Asia, were shown to inhibit parasite growth by 68%. Follow-up studies, however, only achieved 12% to 40% inhibition. Professor Tu reasoned that the low inhibition could be due to a low concentration of the active ingredient in the preparation and began to improve the methods of extraction. After reading the ancient Chinese medical description, “take one bunch of Qinghao, soak in two sheng (~0.4 liters) of water, wring it out to obtain the juice and ingest it in its entirety” in The Handbook of Prescriptions for Emergency Treatments by Ge Hong (283–343 CE) during the Jin Dynasty, she realized that traditional methods of boiling and high-temperature extraction could damage the active ingredient. Indeed, a much better extract was obtained after switching from ethanol to ether extraction at lower temperature.
However, the extract was still toxic.Professor Tu then further removed from the extract an acidic portion that contained no antimalarial activity, leaving a neutral extract with reduced toxicity and improved antimalarial activity. The neutral extract, termed extract number 191, was tested in the mouse malaria, Plasmodium berghei, and achieved 100% inhibition in October 1971. She presented her findings at a 523 meeting held in Nanjing on March 8, 1972, providing some critical parameters for other teams to quickly obtain pure artemisinin crystals. Although Tu’s team struggled to obtain high-quality crystals from the plant in the following months, two teams (Zeyuan Luo, Yunnan Institute of Drug Research and the late Zhangxing Wei, Shandong Institute of Chinese Traditional Medicine), using the information and methods she used, soon obtained pure crystals from A. annua L. that were highly active against rodent malaria parasites. Tests in humans by Guoqiao Li, Guangzhou University of Chinese Traditional Medicine, using the artemisinin crystals from Yunnan Institute of Drug Research showed good activity against malaria infection.
Interestingly, the paper describing artemisinin’s X-ray crystal structure, pharmacology, and efficacy against non-severe and severe cerebral malaria listed no specific authors, who were identified instead as the Qinghaosu Antimalarial Coordinating Research Group (1979). The paper showed that artemisinin is a sesquipene lactone with an endoperoxide, and that the endoperoxide is required for its antimalarial activity (Figure 1). In 1985, Klayman, working in the US at the Walter Reed Army Institute of Research (WRAIR), described the isolation of the same compound and its structure from Artemisia annua (sweet wormwood), which grew along the shores of the Potomac River. Klayman pointed out that there are few naturally occurring endoperoxides described in plants. Although numerous hydroxoperoxides had been tested at WRAIR, none were found to have antimalarial activity (Klayman, 1985).