News Ancient Chinese anti-fever cure becomes panacea for malaria malarial treatment for stricken soldiers. The son of peasants, Professor Zhou Yiqing was born in This was classified as a top secret state 1929. He joined the Eighth Route Army (later part of the mission named Project 523, after the People’s Liberation Army) at the age of 16. During the date, 23 May 1967, it was established. Sino-Japanese War and the War of Liberation (Chinese Civil War) he served as a nurse, head of a nursing squad, Q: What made you and your team think assistant physician and eventually doctor-in-charge. of using artemisinin to treat malaria? In 1960, he graduated from the Shanghai No. 2 Military A: Project 523 included two groups Medical University and later became a researcher at the engaged in antimalarial drug develop- WHO/Cui Weiyuan WHO/Cui Institute of Microbiology and Epidemiology (IME) of the ment: one to devise chemical medi- Professor Zhou Yiqing Chinese Academy of Military Medical Sciences (AMMS). cines, another to examine traditional Chinese medicines. The latter group included researchers as well as tradi- tional Chinese medicine doctors, who, In April this year, Zhou Yiqing and his team won the 2009 European Inventors of as part of Chairman Mao’s barefoot the Year award (in the non-European countries category) for developing the first scheme, scoured the nation to collect artemisinin-based combination therapy (ACT) for malaria, known as Coartem. He talks folk remedies. By the time Project to reporter Cui Weiyuan about this achievement. 523 had got under way, the Cultural Revolution had started and the research provided shelter for scientists facing Q: Did malaria ever affect people in vowed to improve myself. In 1960, I political persecution. From 1970, the China? graduated from medical school and focus of the project shifted to traditional was assigned to become a researcher at A: Malaria was an epidemic disease in Chinese medicine because producing the Chinese AMMS but was first sent China for more than 3000 years. The antimalarials became less of a priority to the Soviet Union for further study. symptoms were described in ancient after China produced chemical combi- Contracting malaria made me realize writings. For example, Nei Jing (the nation antimalarials and provided them how bad the disease can be. However, Canon of Internal Medicine) described to North Viet Nam. Experts screened my official participation in the research them as early as 270 BC. When a list of herbs and folk remedies, a few project stemmed from the Viet Nam the People’s Republic of China was of which were found to have a curative War. When I returned from the Soviet founded in 1949, malaria was endemic effect against malaria. In the end, the Union in 1964, the war had broken in two-thirds of Chinese counties, but Artemisia annua plant was chosen for out. I was ordered to conduct field re- it has not been a major public health further research. In the early 1970s, a search on tropical diseases in Viet Nam. problem since the 1980s. Project 523 team first isolated arte- China was supporting North Viet Nam misinin from the plant. Clinical trials and providing it with medical aid. Q: What was your first experience of confirmed its antimalarial effects. Be- malaria? Following orders, my comrades and I travelled along the Beibu (Tonkin) Gulf tween 1976 and 1978, the molecular A: In the battle to cross the Yangtze and through the Ho Chi Minh Trail structure of artemisinin was identified River in 1949, I contracted the disease in the jungle – it was the only way to and more artemisinin derivatives were for the first time and suffered recurring maintain supplies for North Viet Nam developed. In 1979, artemisinin-based bouts. No effective medicine was avail- because the United States of America antimalarial drugs were first used in the able. The pain left a sharp impression had bombed it so intensely. We were battlefield in the Sino-Vietnamese War on me. I received an arsenic injection accompanied by showers of bombs (the Third Indo-China War). Chinese and, later, Atabrine (quinacrine) pills. during the trip. There, I witnessed scientists in Project 523, unlike West- The pills made me turn bright yellow. rampant malaria that reduced the com- ern researchers looking to find new Although the side-effects were serious, bat strength by half, sometimes by up medicines, identified herbs with cura- I survived. Some female comrades to 90% when the soldiers became ill. tive effects first, before targeting active suffered psychosis from drug toxicity There was a saying, “We’re not afraid ingredients, drawing on their knowl- after being treated. of American imperialists, but we are edge of traditional Chinese medicine. afraid of malaria,” although in fact the Q: Is that what spurred you to do research disease took a huge toll on both sides. Q: What was artemisia annua tradition- to find antimalarial drugs? Later, we submitted a report to China’s ally used for in China? A: While I worked as a battlefield Central Military Committee, stressing A: As early as the second century BC, doctor, one thing bothered me most: the importance of developing China’s the Qinghao plant (sweet wormwood) wounded soldiers begging me to save own antimalarials. Taking our advice, had appeared as an anti-fever medicine their lives because sometimes I just the central government set up a panel in the Fifty-two remedies, a medical could not help them. I had only four of more than 500 medical military and treatise. In 340 BC, the Artemisia an- years’ primary school education. I civilian experts to develop new anti- nua plants were first described as having Bull World Health Organ 2009;87:743–744 | doi:10.2471/BLT.09.051009 743 News antimalarial properties by Ge Hong, Q: What role did the World Health duced me to China International Trust an alchemist and medical expert of the Organization (WHO) play in the early and Investment Corporation (CITIC), East Jin Dynasty. The folk remedies development of ACT? the only Chinese state enterprise at that Project 523 collected around the A: In the early 1980s it seemed that the time that was authorized to deal 1970s also registered these usages. antimalarial research was over for good. with foreign investors. With the State’s Fortunately, essays published by Project approval and CITIC’s help, we were Q: Why did you research ACT for 523 scientists caught the eye of WHO. introduced to Novartis. At first, we malaria at a time when there were no In around 1979, TDR (Special Pro- were wary about dealing with a Western concerns about resistance to artemisinin? gramme for Research and Training in team, but soon the mistrust melted away because of their professionalism A: There was a risk of resistance in Tropical Diseases) [sponsored by the and eagerness to cooperate. theory, even though artemisinin United Nations Children’s Fund, the could kill the blood parasite before United Nations Development Pro- Q: How did you and your team manage quickly evacuating the body, allowing gramme, the World Bank and WHO] to patent Coartem? no time for drug resistance to build expressed interest in cooperation on up. We also found that artemisinin, antimalarial research. But after Proj- A: China passed its first Patent Law in when used alone, cannot clear all ect 523 was disbanded in 1981, there 1985. Due to the previous absence of a the parasites. But combined with was no one to negotiate the issue. In patent law, the molecular structure of lumefantrin, the ACT eliminates any 1981, TDR held the first international artemisinin and its derivatives had been residual parasitic stragglers. Mean- conference in Beijing on artemisinin published in the late 1970s and early while, through screening Plasmodium and its variants. The next year, thanks to 1980s, and therefore patents for those formulas could no longer be registered. falciparum models for AMMS and WHO/TDR’s efforts, the National Chi- The ACT that later became known as other research institutes, I learned the nese Steering Committee for Develop- Coartem was the only invention we characteristics of different antima- ment of Qinghaosu and its Derivatives had that was still patentable. In 1990, larials and had the new synthetic was set up under the Ministry of Health my team and I applied for the original antimalarials to hand. Consequently, to replace Project 523. The project patent in China. [Editor’s note: the I proposed a project to delay possible was saved. Although the cooperation between the National Committee patent was only granted in 2002 under drug resistance to artemisinin and its Chinese patent law that was revised variants. With permission from the and WHO and TDR was suspended, they continued to provide support. in 1993.] The patent now belongs to National Chinese Steering Commit- my institute, IME, and the nation. tee for Development of Qinghaosu My research was informed by WHO guidelines. Chinese scientists at the time In 1991, to help our team get patents (artemisinin) and its Derivatives, I around the world, Novartis established started the research on ACT in 1981. had never seen those guidelines, which had become standard in the West. a partnership with the IME/AMMS For four years, I worked virtually and Kunming Pharmaceutical Corpora- on my own. The only assistant I had WHO also provided us with researcher exchange opportunities and training. tion, through CITIC. Together, we co- thought her job was to transform my developed Coartem. In 1994, Novartis mind revolutionarily, a leftover from received worldwide licensing rights for Q: Why did you introduce ACT outside the Cultural Revolution.