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| MEDICAL HISTORY PAGE |
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| Year : 2014 | Volume
: 5
| Issue : 2 | Page : 191-192 |
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Discovery of artemisinin: The Chinese wonder drug
Padmaja Udaykumar
Department of Pharmacology, Father Muller Medical College, Mangalore, Karnataka, India
| Date of Web Publication | 1-Jul-2014 |
Correspondence Address:
Padmaja Udaykumar
1474, Raag, 1st Cross, Falnir Road, Mangalore - 575 002, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0975-9727.135780
Artemisinin, a great boon to the patients of multidrug-resistant malaria, has an equally amazing history. Although used by the Chinese herbal healers centuries ago, its introduction to the modern system of medicine was preceded by extensive research. The success of 'project 523' is further evidence to the medical fraternity that collaborative research can yield rich dividends. Although many claim credit, Dr. Youyou Tu was awarded the Lasker prize for the feat. Keywords: Artemisinin, history, Lasker award, malaria
How to cite this article:
Udaykumar P. Discovery of artemisinin: The Chinese wonder drug. Muller J Med Sci Res 2014;5:191-2 |
The discovery of artemisinin deserves its place as a 'breakthrough' in the history of medicine. Though the drug has been in use since centuries in the Chinese traditional medicine, its acceptance into modern medicine is fairly recent. In the 1960s, the "jungle war" broke out between the North Vietnam and the United States. [1] The Vietnamese soldiers were dying of chloroquine-resistant malaria. It was then that they appealed to China to find a remedy for this dreaded disease. The situation was as bad on the American side and this initiated extensive research by both factions. The Walter Reed Army Institute of Research started search for malaria cure which resulted in the synthesis of mefloquine. Although it was an effective drug, mefloquine caused several side effects including the CNS effects like nightmares, psychotic behavior including paranoia. Many soldiers even refused to take the drug as stories went round that mefloquine had driven many of them insane.
In response to the Vietnamese' pleas, Mao Zedong of China ordered his scientists to search for a cure for malaria. On May 23 rd 1967, the "project 523" was launched. [2] However, at that time, there was an ongoing cultural revolution in China, where intellectuals including scientists were ill-treated, forced to work in farms which even led to many suicides. Since project 523 was initiated from Mao Zedong and the army was in charge of the project, it gained importance and over 500 scientists working in 60 institutes were roped in to carry out the task. They were grouped into two teams, of which one screened synthetic chemicals (~40,000 compounds) and the other studied the traditional Chinese medicine recipes (about 2000 recipes) likely to have antimalarial activity. Envoys were sent to villages to collect information from herbal healers about their "secret cures" for fever. The project was a well-guarded military secret but the inner circle scientists and research groups were kept informed about the progress. Qinghao or Artemisia annua identified by rural healers is a type of worm wood native to Asia and was said to be useful in fevers as even mentioned in the tomb carvings (168 BC). Extracts from Qinghao inhibited the parasite growth to some extent. Prof. Youyou Tu was a principle investigator at the institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (CACAMS). Working on Qinghao, she improvised the method of extraction, used ether extraction and also removed an acidic component to obtain a neutral abstract. The neutral extract was less toxic, more effective with better antimalarial activity and achieved 100% inhibition when tested in mouse malaria in Oct 1971. Zhangxing Wei obtained pure crystals from the extract and this was used in humans by Guoqiao Li to obtain good results. Further research on the chemistry showed that the chemical now called artemisinin is a sesquiterpine lactone. In 1985 Klayman from Walter Reed army institute of research isolated the same compound from Artemisia annua which grew along the shores of Potomac River. Clinical studies by Guoqiao Li and his team comparing artemisinin with mefloquine suggested that combination therapy should be considered to prevent recurrence and resistance. Artemisinin was eliminated quickly from the body and also the patients discontinued treatment due to quick recovery, only to have recurrence/recrudescence. Such incomplete treatment would also encourage the development of resistance. Other drugs developed by the project 523 were lumefantrine, piperaquine, and pyronaridine. After Mao Xedong's death in 1976, the Project 523 was officially closed in 1981. The success of the project emphasizes the importance and advantages of collaborative work.
On learning the path breaking discovery by the Chinese, Nick White studied the effects of artemisinin derivatives and confirmed both their efficacy and need for an additional drug. In 2010 he was awarded the Canadian Gadgner award for his work. Dr. Keith Arnold who was involved in mefloquine development, conducted studies with Guoqiao to compare mefloquine with artemisinin and reported that the Chinese mystery drug beat his. [3]
The Chinese researchers published an article on artemisinin in the Lancet in 1982 but the prize money they won could not be encashed as it was in British Pounds. Though the Chinese 'wonder drug' was thus brought to light by several researchers, it was not given its right place by the W.H.O till 2000. As the drug did not receive W.H.O. approval, it was not widely available. The death of almost 1 million children in Africa due to malaria could well be the unfortunate consequence of this apathy. Novartis, a pharmaceutical company finally bought a patent of a combination of artemether and lumafantrine. Though it was bought with huge profits in mind, it ultimately started selling it to WHO at a very low price in 2001. The credit for discovery of artemisinin could not be given to one person as multiple contributors were involved. Ten team leaders were identified by a Hong Kong science foundation in 1996. However, the Lasker committee gave Youyou Tu the credit and she received the Laskar award of $250,000. Many prominent malaria researchers including Dr. N.J. White, [4] Dr. Arnold, and Dr. R.K. Haynes did not agree with the decision of crediting it to one person while Dr. Tu defended it saying she was the first to isolate the active ingredient from Qinghao, used the right technique for extraction, even consumed the drug (with her two colleagues) to prove its safety and was also selected to receive the Chinese government's award for project 523.
The discovery of artemisinin is a gift to the mankind in its fight against malaria. A grieving son in his father's funeral was overheard saying "My father was a great man. I can't believe a small mosquito could kill him". In fact, this could well be true to the human race itself as even small microbes like bacteria or virus could someday be great threats to human existence, given the way they have been offering resistance to the existing antimicrobials. Hope nature has kept in store more wonder drugs like artemisinin for us.
| References | |  |
| 1. | Miller LH, Su X. Artemisinin: Discovery from the Chinese herbal garden. Cell 2011;146:855-8. 
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| 2. | Neill US. From branch to bedside: Youyou Tu is awarded the 2011 Lasker~DeBakey Clinical Medical Research Award for discovering artemisinin as a treatment for malaria. J Clin Invest 2011;121:3768-73.
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| 3. | Donald G, Mc Neil Jr. For intrigue, malaria drug gets the prize. From The New York Times. Published Jan 17, 2012. Available from: http://www.globalhealthprogress.org/intrigue-malaria-drug-gets-prize [Last accessed on 2014 May 10].
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| 4. | Ahuja A. Nick White, malaria and artemisinin. Wellcome Trust. Available from: http://www.wellcome.ac.uk/About-us/75th-anniversary/WTVM051627.htm [Last accessed on 2014 May 10].
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