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

StephenW

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

• Youyou Tu
  

Nature Medicine 17,1217–1220(2011)doi:10.1038/nm.2471        Published online11 October 2011   

Joseph Goldstein has written in this journal that creation (through invention) and revelation (through discovery) are two different routes to advancement in the biomedical sciences1. In my work as a phytochemist, particularly 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 (previously 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 training guided me to the wonderful treasure to be found in Chinese medicine and toward understanding the beauty in the philosophical 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 leadership of the Project 523 office. My institute quickly became involved in the project and appointed me to be the head of a malaria 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 investigated more than 2,000 Chinese herb preparations 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 subsequent experiments and appeared to be contradictory to what was recorded in the literature.
Seeking an explanation, we carried out an intensive review of the literature. The only reference 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 extraction step we had used might have destroyed the active components, and that extraction at a lower temperature might be necessary to preserve antimalarial activity. Indeed, we obtained much better activity after switching to a lower-temperature procedure.
                                                                                                                                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.)
                                                                                                                                 We subsequently separated the extract into its acidic and neutral portions and, at long last, on 4 October 1971, we obtained a nontoxic, neutral extract that was 100% effective against parasitemia in mice infected with Plasmodium berghei and in monkeys infected with Plasmodium cynomolgi. This finding represented the breakthrough in the discovery of artemisinin.
Figures at a glance  

•