Tu Youyou and the 523 mission reveal anti-malaria research during the Cultural Revolution

　　According to CCTV News, at the invitation of the Nobel Prize Committee, Chinese scientist Tu Youyou left for Stockholm, Sweden today to deliver a keynote speech on "The Discovery of Artemisinin: A Gift from Traditional Chinese Medicine to the World" on December 7, local time, and attend the Nobel Prize Award Ceremony on the 10th.

　　“The scientific research on "artemisinin" started in China as early as 1967. At that time, the Chinese government wanted to solve the problem of preventing and treating drug-resistant malaria. It organized more than 60 scientific research units and more than 500 researchers across the country to establish a national malaria prevention and control research leading group. This was also the beginning of the mysterious "523 Mission." Thus, the research on antimalarial drugs began in the history of national scientific research.

　　Rao Yi, Zhang Daqing and others recorded in "Youyou and Artemisinin: Tu Youyou and Artemisinin" (China Science and Technology Press, October 2015) that in an era when politics takes the lead, politics profoundly affects the development of scientific research work. According to the information currently available, during the entire "523 Mission", there were fifty or sixty meetings of various sizes. Through these meetings, not only can an overview of the entire "523 Mission" be outlined, but also the interactive relationship between politics and science during the period can be demonstrated from one aspect.

　　The Paper has been authorized to excerpt some of the more important and special meetings in the "523" mission mentioned in "You You You Hao".

　　In the 1950s, Tu Youyou (front right), a research intern at the Institute of Traditional Chinese Medicine of the Academy of Traditional Chinese Medicine, studied traditional Chinese medicine with her teacher, Associate Professor Lou Zhicen.

　　1. Coordination meeting at the beginning of the mission

　　1967 was the year of the Cultural Revolution. Although most scientific research work was at a standstill, it could still be continued because the "523 Task" came from the top leaders. The first meeting held in May 1967 to launch a national malaria prevention and control research collaboration has been introduced in detail in the previous chapter, and its importance is self-evident.

　　2. Task reinforcement meeting

　　From February 21st to February 29th, 1968, the National Science and Technology Commission and the General Logistics Department jointly held the second national collaboration meeting at the Pingfengshan Workers' Sanatorium in Hangzhou to further implement the tasks of the first national collaboration meeting in Beijing on May 23, 1967. The meeting summarized the achievements in anti-malarial research since the first collaboration meeting in May 1967, and specifically arranged various tasks for the year. Minutes of the meeting were issued and reported to the central government. “The various research plans and organizational management agencies of the "523 Mission" have since been on the right track. After the meeting, in addition to the minutes of the meeting, some regulations related to the discussions at the meeting were also issued. In order to strengthen leadership, division of labor and collaboration, clarify tasks, and clarify responsibilities, the responsibilities of various departments, regions, units, and majors have been divided accordingly.

　　On January 15, 1969, revolutionary committees were established in various provinces, cities, and districts. In order to enable the revolutionary committees at all levels to strengthen their leadership in malaria prevention and research work, the Military Control Commission of the State Science and Technology Commission and the General Logistics Department wrote a "Situation Report and Request for Instructions on Malaria Prevention and Research Work" to the Prime Minister and the Central Military Commission. The report recommends convening a symposium in Beijing or Guangzhou with the responsible comrades in charge of this work from the provincial, municipal, and district revolutionary committees, military region logistics departments, and relevant units responsible for notification.

　　Premier Zhou gave specific instructions on the venue of the meeting: “I would like to agree that it would be better to hold this symposium in Guangzhou. ”On January 24, Chairman Mao reviewed this request for instructions report.

　　On February 8, 1969, a special telegram was issued by Premier Zhou Enlai. The contents of the telegram were:

　　Notice on convening a symposium on malaria prevention and control research:

　　With the approval of the great Chairman Mao, it was agreed to hold a symposium on malaria prevention and control research in Guangzhou. Personnel participating in the meeting and related issues will be handled by the State Science and Technology Commission, the Ministry of Health and Military Control in consultation with the General Logistics Department. The specific meeting time and location will be announced later.

　　According to Shi Linrong, a staff member of the “523 Office” at the time:

　　At that time, a staff officer of the General Logistics Headquarters and later a division chief obtained the document, and called Minister Zhang Jianfang and others to display it in a place (the south gate of our hospital).

　　According to Director Zhang Jianfang’s recollection:

　　At that time, the document that Chairman Mao circled was taken to the Academy of Military Medical Sciences by the General Logistics Department, and everyone was summoned to the entrance of the hospital to greet it. Everyone thought that Chairman Mao had given instructions to the hospital, but in fact, everyone saw nothing. I saw circles drawn with red and blue pens on it.

　　3. The 1971 Guangzhou Conference—further strengthened the “523 Mission””

　　As the Cultural Revolution deepened, the operations of national ministries, local administrative agencies and scientific research units fluctuated many times due to the movement. The entire leadership and organizational system also underwent great changes. The new appointees did not necessarily know the importance of this task, and difficulties arose in the implementation of the "523 Task". The three-year malaria prevention and control research plan established in 1967 has also expired. Therefore, the Military Control Commission of the Ministry of Health, the Ministry of Fuel and Chemical Industry (hereinafter referred to as the Ministry of Chemical Industry), the Chinese Academy of Sciences, and the General Logistics Department reported to the State Council and the Central Military Commission on March 16, 1971, a "request report on malaria prevention and control research work." The report recommends that the leading group be adjusted, with the Ministry of Health as the leader and the General Logistics Department as the deputy leader, with the office still located at the Academy of Military Medical Sciences. On April 15, 1971, the State Council and the Central Military Commission issued (71) Guofa Document No. 29, giving instructions on the "Request for Instructions Report". On May 22 of the same year, the National Symposium on Malaria Prevention and Control Research was held in Guangzhou. At the meeting, the "523 Leading Group" was composed of the original National Science and Technology Commission (chief leader), the General Logistics Department of the Chinese People's Liberation Army (deputy leader), the Commission of Science, Technology and Industry for National Defense, the Ministry of Health, and the Ministry of Chemical Industry. , the six departments of the Chinese Academy of Sciences were changed to be led by the Ministry of Health (chief leader), the Ministry of Health of the General Logistics Department (deputy leader), the Ministry of Chemical Industry, and the three departments and one hospital of the Chinese Academy of Sciences. In addition, the meeting also formulated a five-year plan for national malaria prevention and control research from 1971 to 1975. According to relevant personnel's recollections, someone at the meeting complained that "523" was about to become "disappeared" and hoped that the central government would support the continued work and strengthen research. On May 28, the meeting conveyed the instructions written by Premier Zhou to Xu Jingxian, then deputy director of the Shanghai Revolutionary Committee. The letter reported that Sihanouk's personal doctor Arish donated a malaria treatment prescription to China. The contents of Premier Zhou’s instructions are:

　　Comrades Xie Hua and Wu Jieping please read this letter and submit it to the relevant units of the Academy of Medical Sciences and the Academy of Military Medical Sciences for further research to see if this prescription can be used to send one or two teams to Hainan Island and Xishuangbanna, Yunnan, where there are falciparum malaria areas for field trials. If it is effective, we can supply a large amount of it to the Indochina battlefield, because they are suffering from this.

　　On May 29, the Ministry of Health convened responsible comrades from the General Logistics Department, the Ministry of Health, the Chinese Academy of Medical Sciences, and the Academy of Military Medical Sciences to conduct research, formulate a trial plan, and report to the Prime Minister. Prime Minister's instructions: Agree in principle to do so.

　　Premier Zhou's instructions are good news for researchers and play an important role in strengthening the leadership and implementation of the "523 Mission". Before this meeting, the Institute of Traditional Chinese Medicine of the Academy of Traditional Chinese Medicine had planned to cancel the project, but it did not receive approval from the Ministry of Health. After the meeting, the Revolutionary Committee and the Military Control Commission of the Institute of Traditional Chinese Medicine strengthened leadership according to the requirements of their superiors, further deployed and equipped scientific research backbones, and formed a research team to ensure the progress of the work. Tu Youyou mentioned the importance of this meeting. After the meeting, the Institute of Traditional Chinese Medicine reorganized the anti-malarial research team to carry out anti-malarial efficacy screening research. Through the efficacy screening of more than 380 extracted samples of more than 200 traditional Chinese medicines, the final focus was on Artemisia annua. Therefore, it can be said that this meeting in 1971 played a very important role in the continuation of the entire "523 Mission" and the rediscovery of the anti-malarial effect of Artemisia annua.

　　At this meeting, a research plan for the next five years was drawn up. At this meeting, the malaria prescription presented by Sihanouk's personal doctor was mentioned. In fact, it was very similar to the "Fang 2" previously studied by the People's Liberation Army's Houzi 236 Unit, with only slight modifications in dosage.

　　4.1973 Shanghai Conference—consolidation and deepening of tasks

　　On the one hand, with the signing of the Vietnam Armistice Agreement, people may have become less ideological about combat readiness tasks; on the other hand, the difficulties in scientific research work itself have made some scientific researchers less confident. In order to check the implementation of the five-year plan for malaria prevention and control research, summarize and exchange experience, coordinate tasks and further promote the development of anti-malaria research, on February 15, 1973, the Ministry of Health, the Ministry of Combustion and Chemical Engineering, the Chinese Academy of Sciences, and the General Logistics Department wrote a "Report on the Status of Malaria Prevention and Control Research" to the Prime Minister, reporting on the implementation of the State Council and the Central Military Commission's "71" National Document No. 29 and the five-year plan. The implementation status was reported on the trial of the French doctor Alish's prescription in compliance with the instructions of the Prime Minister. It was proposed that in order to meet the needs of domestic malaria prevention and treatment, three anti-malarial tablets and other prevention and treatment drugs should be promoted and used in some key epidemic areas in the country in addition to ensuring aid to Vietnam; malaria prevention and treatment research was included in the national key research plan; instructions were requested to convene a symposium on malaria prevention and treatment research and adjust the tasks for the next three years after the implementation of the five-year research plan.

　　Following the approval of the State Council, a symposium on malaria prevention and control research was held in Shanghai from May 28 to June 7 of that year. The meeting was attended by relevant responsible comrades from the Ministry of Health, the State Council Science and Education Group, the Ministry of Chemistry, the Chinese Academy of Sciences, the General Logistics Department, comrades and professional group representatives from relevant provinces, municipalities, autonomous regions, military regions and relevant departments and units, as well as representatives from the schistosomiasis control leading group offices of 13 central and southern provinces, municipalities and autonomous regions, and the Ministry of Commerce. A total of 86 people attended the meeting.

　　The focus of this meeting is:

　　(1) Strengthen the importance of the task. Although the Vietnam Armistice Agreement has been signed, it is emphasized that everyone cannot relax their minds. Malaria prevention and control is still a major task of military health security. On the other hand, domestic malaria has rebounded in recent years, seriously affecting people's health, industrial and agricultural production, and combat readiness. Therefore, prevention and control research tasks are still very arduous. The meeting also stated: "The current issue is not to stop, but to speed up; we cannot weaken, we can only strengthen, and we must achieve results as soon as possible. This is the glorious task entrusted to us by the party and the people." ”From this, it can be inferred that some units were indeed loose-minded at that time, which also better reflects the importance of this meeting.

　　(2) Adjust the tasks for the next three years after the implementation of the five-year plan, and further put forward corresponding tasks and requirements for ten research topics based on the original plan.

　　(3) According to Task 321 of the 1973 Science and Technology Development Plan of Relevant Ministries and Commissions of the State Council, malaria prevention and control research work has been included in the scientific research plans of relevant provinces, municipalities, autonomous regions, departments, and units. Regular inspections are required, and the professional and technical personnel participating in this task are required to remain relatively stable. Emphasize that offices at all levels must do a good job in organizational collaboration and task coordination.

　　5. Chengdu Conference in April 1975 - Comprehensive deployment of artemisinin research work

　　Artemisinin.

　　From February 28 to March 1, 1974, some personnel studying Artemisia annua (Artemisia annua) from Beijing, Shandong, and Yunnan and leaders of the “523 Office” held a symposium on Artemisia annua special research at the Institute of Traditional Chinese Medicine. This part has been introduced previously.

　　From April 14 to April 24, 1975, the “523” Traditional Chinese Medicine Professional Symposium was held in Chengdu. A total of 62 people attended the meeting, including professional representatives from Beijing, Shanghai, Jiangsu, Guangdong, Guangxi, Sichuan, Yunnan, Shandong and other places who participated in the May 23 Traditional Chinese Medicine Research, representatives from relevant units in Henan, Hunan and Hubei, as well as veteran traditional Chinese medicine practitioners and barefoot doctors. At the meeting, various research units reported and exchanged the progress of various research work. The meeting specifically mentioned that the Chinese Medicine Research Group of Guangdong College of Traditional Chinese Medicine has been going deep into malaria-prone rural areas for eight years, accumulated experience in treating cerebral malaria, and achieved good results. At the same time, it was also mentioned that some units focus on laboratory research and have a tendency to improve behind closed doors.

　　The conference focused on artemisia annua research. In particular, Li Guoqiao's group from the Guangdong College of Traditional Chinese Medicine reported at the conference the efficacy of using astragalus provided by Yunnan Medicine to treat 18 cases of malaria, especially falciparum malaria and cerebral malaria. The effect was very obvious, which greatly encouraged the participants, especially the members of the Chinese herbal medicine group. At the same time, there were some reports on other Chinese herbal medicines, such as reports on the anti-malarial effects of eagle claw A and agrimony. As mentioned in the "Late Report", this meeting is the beginning of important arrangements for the first major battle in Artemisia annua (Artemisia annua) research. After this meeting, on the basis of the original research, various units organized and collaborated to conduct research on simple preparations of Artemisia annua, which laid the foundation for improving the production process, investigating resources, and later transforming the chemical structure. This meeting also deployed research on artemisinin derivatives, but since it is not within the scope of this article, it is not covered here.

　　6. Nanning meeting—preparatory meeting before identification of artemisinin.

　　In May 1977, the national “523 Office” held a “Professional Conference on Research on Integrated Traditional Chinese and Western Medicine for the Prevention and Treatment of Malaria Drugs” in Nanning, Guangxi. This conference summarized and evaluated the research progress of artemisinin in the two years since the Chengdu Conference, put forward task requirements that must be completed before the results are identified, and made specific deployments and arrangements. It was a preparatory meeting before the identification.

　　7.1978 Yangzhou-Artemisinin Appraisal Meeting

　　This meeting can be regarded as a summary of artemisinin research, but it is only a summary of one phase of research. This is the first time the birth of China's new anti-malarial drug has been announced to the outside world, and it is also the first meeting with media participation since the launch of the mission. Details about this meeting will be introduced in detail in later chapters.

　　8.1981 Beijing - Symposium of comrades responsible for malaria prevention and control research leading groups and offices in various regions

　　From March 3 to 6, 1981, a “symposium of comrades responsible for malaria prevention and control research leading groups and offices in various regions” was held in Beijing. In 1980, corresponding preparatory meetings had been held and a lot of preparation work had been done. For example: On June 13, 1980, a national "523" leadership group meeting was held in Beijing. Relevant responsible comrades from the National Science and Technology Commission, the State Administration of Medicine, the Ministry of Health of the General Logistics Department, the Academy of Military Medical Sciences and other departments attended the meeting. The meeting was chaired by Huang Shuze, Vice Minister of the Ministry of Health. The meeting affirmed the "523" working method and its results in the past 13 years, and also made corresponding provisions for the subsequent adjustment of working methods, and made preparations for the subsequent dismantling of the national and regional malaria prevention and control research leading groups and offices. Make corresponding preparations; in August of the same year, the four leading departments of the Ministry of Health, the National Science and Technology Commission, the State Administration of Medicine, and the General Logistics Department jointly requested instructions from the State Council and the Central Military Commission to incorporate malaria prevention and control scientific research projects into the provincial and municipal plans of relevant ministries and commissions, and to cancel the national collaborative organization. The 1981 annual meeting mainly adjusted the 523 cooperative organizations. Although the organizational form of 523 has changed, the malaria prevention and control research tasks, as key medical and health research projects, are included in the regular scientific research plans of relevant ministries, commissions, provinces, municipalities, autonomous regions and the military. Moreover, in view of the adjustment of the 523 collaborative organization, the National Ministry of Health established a malaria special committee under the Medical Science Committee. The army also decided to organize the Ministry of Health of the General Logistics Department and planned to establish a malaria prevention and control special group within the epidemiological professional group in May of the same year. On May 11 of the same year, the four leading departments jointly issued the last document as the National Malaria Prevention and Control Research Leading Group - a notice forwarding the "Minutes of the Symposium of Malaria Prevention and Control Research Leading Group and Office Responsible Comrades". In addition to forwarding the minutes of the symposium between the malaria prevention and control research leading group and the comrades in charge of the office, the notice also made an overall plan for the aftermath of the entire May 23 organization. How the files, technical files, funds, materials, etc. of the May 23 office will be transferred will be determined by the competent department of the regional leading group; the relevant competent authorities and the original unit must make appropriate arrangements for the staff who have been away from the original unit for a long time to work full-time in the management of the May 23 scientific research organization.

　　In the 1967 and 1968 meetings, the confidentiality of this task was clearly stipulated. Especially after the 1968 meeting, it was required that drugs for clinical use and finalized production should all use code names. In 1972, in order to more widely introduce and exchange practical experience and achievements in scientific research, when it was requested to summarize and compile the experience and data of malaria research carried out in the past few years, it was proposed that the confidentiality restrictions should not affect the content of the summary when writing. All drugs should not have code names. For convenience of writing, the name of the drug should be indicated the first time a code name is used. In the malaria prevention and control research work briefing in November of the same year, it was stated that the exchange of technical data on malaria prevention and control research that does not involve national or combat readiness secrets (such as the incidence of malaria, the military use of the task, etc.) shall be reviewed and approved by the unit responsible for the task, and may be published in various domestic internal publications in the name of the unit or individual. From the meeting held in Shanghai in 1973, it can be seen that "Mission 523" has begun to slowly transition from combat readiness tasks to routine tasks. Later, confidentiality was even worse than before. Many units that were not originally responsible for the "523 tasks" also joined in when some units were looking for collaborative units, and there was no mandatory requirement not to publish papers. Especially after the first paper was published in the name of the Artemisinin Collaboration Group in 1977, many articles related to structure determination were published one after another. The explicit inclusion of the "523 mission" into the regular scientific research plan was proposed at the National 523 Leading Group meeting in 1980, and then reported to the State Council and the Central Military Commission. It was after the 1981 meeting that the "523 Mission" was officially included in the regular scientific research plans of relevant ministries, provinces, municipalities, autonomous regions and the military.