国外网站关于屠呦呦与青蒿素的介绍

国外网站关于屠呦呦与青蒿素的介绍

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The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine

Youyou Tu

Joseph Goldstein has written in this journal that creation (through invention) and rev-elation (through discovery) are two different routes to advancement in the biomedical sci-ences1. In my work as a phytochemist, par-ticularly during the period from the late 1960s to the 1980s, I have been fortunate enough to travel both routes.

I graduated from the Beijing Medical University School of Pharmacy in 1955. Since then, I have been involved in research on Chinese herbal medicine in the China Academy of Chinese Medical Sciences (pre-viously known as the Academy of Traditional Chinese Medicine). From 1959 to 1962, I was released from work to participate in a training course in Chinese medicine that was especially designed for professionals with backgrounds in Western medicine. The 2.5-year train-ing guided me to the wonderful treasure to be found in Chinese medicine and toward understanding the beauty in the philosophi-cal thinking that underlies a holistic view of human beings and the universe.

Discovery of antimalarial effect of qinghaoMalaria, caused by Plasmodium falciparum, has been a life-threatening disease for thousands of years. After the failure of international attempts to eradicate malaria in the 1950s, the disease rebounded, largely due to the emergence of parasites resistant to the existing antimalarial drugs of the time, such as chloroquine. This created an urgent need for new antimalarial medicines. In 1967, a national project against malaria was set up in China under the lead-ership of the Project 523 office. My institute quickly became involved in the project and appointed me to be the head of a malaria

Youyou Tu is at the Qinghaosu Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

e-mail: youyoutu1930cn@http://doc.guandang.net

Figure 1 A Handbook of Prescriptions for Emergencies by Ge Hong (284–346 CE). (a) Ming dynasty version (1574 CE) of the handbook. (b) “A handful of qinghao immersed with 2 liters of water, wring out the juice and drink it all” is printed in the fifth line from the right. (From volume 3.)

research group comprising both phytochemical and pharmacological researchers. Our group of young investigators started working on the extraction and isolation of constituents with possible antimalarial activities from Chinese herbal materials.

During the first stage of our work, we inves-tigated more than 2,000 Chinese herb prepara-tions and identified 640 hits that had possible antimalarial activities. More than 380 extracts obtained from ~200 Chinese herbs were evaluated against a mouse model of malaria. However, progress was not smooth, and no significant results emerged easily.

The turning point came when an Artemisia annua L. extract showed a promising degree of inhibition against parasite growth. However, this observation was not reproducible in subse-quent experiments and appeared to be contra-dictory to what was recorded in the literature.Seeking an explanation, we carried out an intensive review of the literature. The only ref-erence relevant to use of qinghao (the Chinese name of Artemisia annua L.) for alleviating malaria symptoms appeared in Ge Hong’s A Handbook of Prescriptions for Emergencies: “A handful of qinghao immersed with 2 liters of water, wring out the juice and drink it all” (Fig. 1). This sentence gave me the idea that the heating involved in the conventional extrac-tion step we had used might have destroyed the active components, and that extraction at a lower temperature might be necessary to pre-serve antimalarial activity. Indeed, we obtained much better activity after switching to a lower-temperature procedure.

nature medicine

国外网站关于屠呦呦与青蒿素的介绍

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covery of artemisinin was the first step in our advancement—the revelation. We then went on to experience the second step—creation—by turning the natural molecule into a drug.We had found that, in the genus Artemisia, only the species A. annua and its fresh leaves in the alabastrum stage contain abundant artemisinin. My team, however, used an Artemisia local to Beijing that contained relatively small amounts of the compound. For pharmaceutical production, we urgently required an Artemisia rich in artemisinin. The collaborators in the nationwide Project 523 found an A. annua L. native to the Sichuan province that met this requirement.

The first formulation we tested in patients was tablets, which yielded unsatisfactory results. We found out in subsequent work that this was due to the poor disintegration of an inappropriately formulated tablet produced in an old compressing machine. We shifted to a new preparation—a capsule of pure artemisi-nin—that had satisfactory clinical efficacy. The road leading toward the creation of a new anti-malarial drug opened again.

Spreading the word

In addition to problems of production and for-mulation, we also faced challenges regarding the dissemination of our findings to the world. The stereo-structure of artemisinin, a sesquit-erpene lactone, was determined with the assis-tance of a team at the Institute of Biophysics, Chinese Academy of Sciences, in 1975. The structure (Fig. 3) was first published in 1977

(ref. 2), and both the new molecule and the paper were immediately cited by the Chemical Abstracts Service in the same year. However, the prevailing environment in China at the time restrained the publication of any papers concerning qinghaosu, with the exception of several published in Chinese2–20. Fortunately, in 1979, the China National Committee of Science and Technology granted us a National Invention Certificate in recognition of the discover …… 此处隐藏：20300字，全部文档内容请下载后查看。喜欢就下载吧 ……