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Parassitologia 50: 25-29, 2008 Artemisinins from Folklore to Modern Medicine - Transforming an Herbal Extract to Life-Saving Drugs P.J. Weina Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland 20910 Abstract. The history of the artemisinins from Ge Hong in China during the 4 th century, to the re-discovery of the qing hao derivatives in the 1970s, to the explosion of artemisinin derivatives and combinations throughout the world today is a fascinating story. The central and underappreciated role of the United States Army’s ‘drug company’ known as the Division of Experimental Therapeutics at the Walter Reed Army Institute of Research is a story worth relating. From being the first group outside China to extract the active component of qing hao, to leading the work on neurotoxicity of the class in animals, to bringing a Good Manufacturing Practices intravenous formulation to the worldwide market is traced. Keywords: Malaria, Artemisinin, Artesunate, Qing hao. The Walter Reed Army Institute of Research (WRAIR) has a group within it called the Division of Experimental Therapeutics. This small of group of physicians and scientists comprise one of the most influential, successful, but relatively unknown antimalarial drug programs in the world. Since World War II, this group has filed over sixty Investigational New Drug Applications with the U.S. Food and Drug Administration for antimalarials and have had a hand in virtually every antimalarial licensed in the developed world. And yet, with all of this history, most of the older researchers and military officers at the WRAIR can still remember the first time they heard about artemisinin. At the time, few people knew it by this name though. Artemisinin was the name used by only a very few scientists and the name used by most researchers “Qing hao su”, had a certain exotic and lyrical ring to it that caught everyone’s attention. Not only its name, but also the remarkable promise of the activity of this new compound captured people’s attention like few other compounds had done in many, many years. The WRAIR always had teams looking for new leads in the field and the WRAIR teams quickly learned of the evolving miracle from the Far East. Dr. Wilbur Milhous, considered by many at the WRAIR as the “village elder” for the Division of Experimental Therapeutics, recalls, “It was 1982 and I was a fellow at Burroughs Wellcome. We received a report from the WHO (World Health Organization) malaria steering group in Geneva saying there was a promising new Chinese plant called qing hao.” Rumors of a miraculous new Chinese cure for malaria had been circulating for years in the very small circle of ‘science geeks’ who specialized in the search for new chemotherapeutic Correspondence: Peter J. Weina PhD, MD, FACP Colonel, Medical Corps, USA Walter Reed Army Institute of Research 503 Robert Grant Avenue Silver Spring, Maryland 20910 Tel: 301-319-9956; fax: 301-319-7360, e-mail: peter.weina@amedd.army.mil drugs for malaria at the time. The Chinese had first published their findings in the Chinese Medical Journal in 1979, but being in Chinese and having limited distribution before the days of the internet explosion, only a few people outside of China knew of their work. When discovered by scientists at the WHO, Chinese scientists were approached for samples of the plant so they could conduct their own assays, but they were rebuffed. Clearly in retrospect, it can appreciated that as this was just after the Nixon era and Mao Tse-tung was still in power, the Chinese were very skeptical about sharing information with the outside world. Their greatest fear was that it would be utilized by large western commercial pharmaceutical companies for monetary gain. Ironically, qing hao had been known to Chinese herbalists for more than 2,000 years. Although there is some confusion regarding the difference between Artemisia annua L. and A. apaicea, known in the 1 st century BC as cao hao (or herbaceous hao) and in the 2 nd century BC as qing hao (or blue-green hao), both were in common use in Chinese herbal medicine and both contain the antimalarial substance artemisinin. Elisabeth Hsu in the Transactions of the Royal Society of Tropical Medicine and Hygiene describes and dissects the sometimes confusing differentiation between the two plants and their use in the Chinese materia medica. This relatively common weed found in many parts of the world is better known to gardeners by its common name, sweet wormwood. Like cinchona, and many other members of the Compositae family to which it is related (sagebrush, tarragon, absinth), sweet wormwood is particularly noted and prized for its aromatic bitterness. For as long as this herb has been known and used though, its soon to be central role in antimalarial usage was only truly appreciated at the height of the Cultural Revolution when Mao ordered his scientists to solve the problem of malaria that was spreading through China’s southern provinces and ravishing the Vietnamese military. Even though well known to people like Ge Hong, who in the 4 th century was the first to write about recommending the drug qing hao for the
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90 (vii) Antimycotic properties, pr
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98 test, whereas for the remaining
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100 pyriproxyfen is twice as biolog
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136 Program financed by ANTIMAL. S.
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148 geographic distribution in sub-
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150 K.E., Beldjord, C., Nagel, R.L.
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