Project 523 (Chinese: 523项目) was a code name for a 1967 secret military project of the People's Republic of China to find antimalarial medications. Named after the date the project launched, 23 May, it addressed malaria, an important threat in the Vietnam War. At the behest of Ho Chi Minh, Prime Minister of North Vietnam, Zhou Enlai, the Premier of the People's Republic of China, convinced Mao Zedong, Chairman of the Chinese Communist Party, to start the mass project "to keep [the] allies' troops combat-ready", as the meeting minutes put it. More than 500 Chinese scientists were recruited. The project was divided into three streams. The one for investigating traditional Chinese medicine discovered and led to the development of a class of new antimalarial drugs called artemisinins. Launched during and lasting throughout the Cultural Revolution, Project 523 was officially terminated in 1981. For their high efficacy, safety and stability, artemisinins such as artemether and artesunate became the drugs of choice in treating falciparum malaria. The World Health Organization advocates their combination drugs and includes them in its List of Essential Medicines. Among the scientists of the project, Zhou Yiqing and his team at the Institute of Microbiology and Epidemiology of the Chinese Academy of Military Medical Sciences, were awarded the European Inventor Award of 2009 in the category "Non-European countries" for the development of Coartem (artemether-lumefantrine combination drug). Tu Youyou of the Qinghaosu Research Center, Institute of Chinese Materia Medica, Academy of Traditional Chinese Medicine (now the China Academy of Traditional Chinese Medical Sciences), received both the 2011 Lasker-DeBakey Clinical Medical Research Award and 2015 Nobel Prize in Physiology or Medicine for her role in the discovery of artemisinin.
Background The Vietnam War was fought between North Vietnam (with support from Communist countries such as Soviet Union and China) and South Vietnam (with support from the United States and its allies). The conflicts began in 1954 and became large-scale battles by 1961. Although in a better warfare position, the People's Army of Vietnam (North Vietnamese Army) and its allies in the South, Viet Cong, suffered increasing mortality because of malaria epidemics. In some battlefields, the disease would reduce military strengths by half and in severe cases, disable 90% of the troops. North Vietnamese Prime Minister Ho Chi Minh asked Chinese Premier Zhou Enlai for medical help. The year before, party Chairman Mao Zedong had introduced the Cultural Revolution, during which he would close schools and universities and banish scientists and intellectuals. Mao took Ho's plea seriously and approved a military project. On 23 May 1967, about six hundred scientists convened. These included military personnel, scientists, and medical practitioners of Western and traditional Chinese medicine. The meeting marked the start of the military-research programme, which received the code name Project 523, after the date (23 May) it launched. The project was divided into three main streams, one for developing synthetic compounds, one for clinical studies (or infection control) and another for investigating traditional Chinese medicine. Classified as a top secret state mission, the project itself saved many scientists from the atrocities of the Cultural Revolution.
Execution and achievements As the first line strategy, the troops were given synthetic drugs. Drug combinations using pyrimethamine and dapsone, pyrimethamine and sulfadoxine, and sulfadoxine and piperaquine phosphate were tested in the battlefield. Because these drugs had serious adverse effects, the primary focus was to examine traditional Chinese medicines and look for new compounds. The first drug of interest was chángshān (常山), an extract from the roots of Dichroa febrifuga depicted in the Shennong Ben Cao Jing. Another early candidate was huanghuahao (sweet wormwood or Artemisia annua). These two plants became a huge success in modern pharmacology.
Febrifugine from chángshān The first interest was on chángshān, the root extract of Dichroa febrifuga. In the 1940s, Chinese scientists had shown that it was effective against different species of Plasmodium. American scientists isolated febrifugine as its major active antimalarial compound. The project scientists confirmed the antimalarial activity but found it unsuitable for human use due to its overwhelming potency and toxicity, outrivaling that of quinine. After the project, the compound remained under investigation, with attempts to discover suitable derivatives, among which halofuginone is an effective drug against malaria, cancer, fibrosis and inflammatory disease.
Discovery of artemisinin and its derivatives
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