Ni Dashi (倪大石, 1925–2022) was a Chinese microbiologist who developed an immunotherapy for epidemic haemorrhagic fever (EHF) in China between 1985 and 1988. Since 1950s, China had been plagued by this disease, urging scientists to dedicate themselves to virus isolation and the exploration of specific treatments. Among them, Ni and his team led the isolation of the virus in China. Building on this breakthrough, Ni developed a transfer factor derived from virus-immunized porcine spleens to modulate patients’ immune responses and alleviate their symptoms. This essay reawakens recognition of Ni's significant yet overlooked contribution to the development of immunotherapy for EHF.
China Health Statistics Yearbook continues to refer to this disease as epidemic haemorrhagic fever, hence in this paper, we have retained the designation EHF. National Health Commission of the People's Republic of China. Zhongguo weisheng jiankang tongji nianjian 2024 [The China health statistics yearbook 2024]. Beijing: Peking Union Medical College Press, 2025.
SheedyJAFroebHFBatsonHA, et al.The clinical course of epidemic haemorrhagic fever. Am J Med1954; 16: 619–628.
4.
LeeHWDalrympleJM. Manual of haemorrhagic fever with renal syndrome. Seoul:WHO Collaborating Center for Virus Reference and Research,1989, pp. 6–8.According to Chinese official statements, “There are no formal reports from the Chinese People's Volunteer Army. Most cases occurred individually.” See Medical Department of the General Logistics Department of the People's Liberation Army. Kangmei yuanchao zhanzheng weisheng gongzuo zongjie: yezhan neike weisheng fangyi [Summary of medical work in the war to resist U.S. aggression and aid Korea: field internal medicine and sanitary prevention]. Beijing: People's Military Medical Press, 1987, p. 221.
5.
ShinM. Becoming an international scientist in South Korea: Ho Wang Lee’s research activity about epidemic haemorrhagic fever. Korean J Med Hist2017; 26: 95–124.
6.
Compilation Group for “Liuxingxing Chuxuere Fangzhi Shouce” of the Department of Disease Control of Ministry of Health. Liuxingxing chuxuere fangzhi shouce [Manual for the prevention and treatment of epidemic haemorrhagic fever]. 2nd ed. Beijing: People's Medical Publishing House, 1987, p. 4.
7.
In 2007, the Anhui Institute of Medical Sciences was renamed the Anhui Academy of Medical Sciences.
8.
Xia M WeiYH (eds). Bainian dangshi zhong de gonggong weisheng [Public health in the century-old history of the Communist Party of China]. Guangzhou: Zhongshan University Press, 2024, pp. 67–68.
9.
Zhang CA (ed). Linchuang geke changjian jibing de zhenliao he huli [Diagnosis, treatment, and nursing care of common diseases in clinical departments]. Shenyang: Liaoning Science and Technology Publishing House, 2011, pp. 654–655.
10.
The United Nations Relief and Rehabilitation Administration (UNRRA) was established in Washington, D.C. in 1943 to provide relief for victims of World War II.JiLH. From humanitarian relief to strategic materials: study on the distribution of medical supplies to China by the UNRRA after the victory ofthe war of resistance against Japan. J Soc Hist Med Health2023; 8, p. 254.
11.
Compilation Committee for Hefei Health Gazetteer. Hefei weisheng zhi [Hefei health gazetteer]. Hefei: Huangshan Publishing House, 2001, p. 612.
12.
In 2003. the HEPS was reorganized into the Anhui Provincial Center for Disease Control and Prevention.
13.
WuMYHongLYNiDS. Hefeishi liuxingxing yixing naoyan bingdu de fenli yu jianding [Isolation and identification of Japanese encephalitis virus in Hefei city]. J Anhui Med Coll. 1958; 1: 10–14.
14.
Compilation Committee for Hefei Health Gazetteer. Hefei weisheng zhi [Hefei health gazetteer]. Hefei: Huangshan Publishing House, 2001, p. 612. Ni’s work on virus isolation was not a national leader, and in a retrospective article summarizing the achievements of medical science in the 10th anniversary of the founding of the new China, Ni’s work was mentioned only in the sense of “skin antigen experiments.” SeeSongG. Liuxingxing yixing naoyan yanjiu de chengjiu [Achievements in research on Japanese encephalitis]. In: Ministry of Health of the People's Republic of China. Qingzhu jianguo shi zhounian yixue kexue chengjiu lunwenji: 1949–1959 [Proceedings of medical science achievements in celebration of the 10th anniversary of the founding of the People's Republic of China: 1949–1959. Vol 2. Beijing: People's Medical Publishing House, 1959, pp. 98–108.
15.
Compilation Committee for Anhui Health Gazetteer. Anhui wei sheng zhi [Anhui health gazetteer]. Hefei: Huangshan Publishing House, 2024, pp. 222–223.
16.
NiDSWangQSZhuXX, et al. Liuxingxing chuxuere bingyuan fenli yanjiu (zhaiyao) [Isolation of pathogens from epidemic haemorrhagic fever (abstract)]. In: Anhui yixue yanjiusuoqingbao ziliaoshi. Liuxingxing chuxuere zhuanji [Epidemic haemorrhagic fever album]. Hefei: Anhui yixue yanjiusuo qingbao ziliaoshi, 1963, p. 359.
17.
WuXK. Anhui liuxingxing chuxuere fangzhi shihua (zhi yi) [A brief history of epidemic haemorrhagic fever prevention and control in Anhui (part one)]. Anhui J Prev Med1999; 5, p. 367.
18.
NiDSWangQSZhuXX, et al. Liuxingxing chuxuere shiyan zhenduan fangfa yanjiu 1 (142 li huan zhe xueqing de ji xueqiu rongjie shiyan jieguo) [A study on laboratory diagnostic methods for epidemic hamorrhagic fever 1 (results of the chicken haemolysis test on sera from 142 patients)]. In: Anhui Yixue YanjiusuoQingbao Ziliaoshi. Liuxingxing chuxuere zhuanji [Epidemic haemorrhagic fever album]. Hefei: Anhui Yixue Yanjiusuo Qingbao Ziliaoshi, 1963, pp. 360–361.
19.
ChungHL, 1963 nian chun canjia Anhui sheng liuxingxing chuxuere fangzhi gongzuo zongjie ji quanguo jishu jingyan jiaoliu huiyi de yixie tihui ganshou he jianyi [Reflections and recommendations from participating in the 1963 Anhui Province Epidemic Haemorrhagic Fever Prevention and Control Work Summary and National Technical Experience Exchange Conference]. In: Anhui yixue yanjiusuo qingbao ziliaoshi. Liuxingxing chuxuere zhuanji [Epidemic haemorrhagic fever album]. Hefei: Anhui yixue yanjiusuo qingbao ziliaoshi, 1963, p. 3
20.
Barefoot doctors were primary healthcare workers under the People’s Commune system from 1968 to 1983. They were usually members of commune production brigades who received only brief medical training, mostly through on-the-job learning, but also included professionals like Ni. SeeFangXP. Barefoot doctors and the provision of rural health care. In: Andrews BBullock MB (eds). Medical transitions in twentieth-century China. Bloomington: Indiana University Press, 2014, pp. 267–282.
21.
Compilation Committee for Hefei Health Gazetteer. Hefei weisheng zhi [Hefei health gazetteer]. Hefei: Huangshan Publishing House, 2001, p. 612.
22.
ZhouN. Personal communication, 5 July 2024.
23.
Shaanxi Health Department, Shaanxi Health and Epidemic Prevention Station and Office of Compilation Committee for Shaanxi Health Gazetteer. Shaanxi sheng yufang yixue jianshi [A brief history of preventive medicine in Shaanxi province]. Xi'an: Shaanxi People's Publishing House, 1992, p. 113.
24.
SongGHangCSQiuXZ, et al.Yong feiyiqu heixian jishu fenli dao liuxingxing chuxuere bingyuan yinzi jianbao (jianbao) [Isolation of EHF—related agent from apodemus agrarius captured in non-epidemic areas (brief report)]. J Chin Acad Medical Sci1982; 4: 66.
25.
NiDS. Cong bingren xueqing zhong fenli de yi zhu liuxingxing chuxuere bingdu de jianding [Identification of a strain of epidemic haemorrhagic fever virus isolated from patient serum]. Anhui yixue [Anhui Med]1983; 4: 193. ZhaoEJ. Liuxingxing chuxuere wenti 205 jie [205 Questions on epidemic haemorrhagic fever]. Beijing: Xuelin Press, 1985, p. 2. Although there is no direct evidence that Ni was aware of Lee's research, the viral transmission methods and cell lines they used were the same. For details regarding Ho Wang Lee's isolation of EHF virus using A-549 cells. See FrenchGRFoulkeRSBrandOA, et al. Korean haemorrhagic fever: propagation of the etiologic agent in a cell line of human origin. Science1981; 211: 1046–1048.
26.
Compilation Committee for Anhui Provincial Local Gazetteers. Anhui shengzhi: kexue jishu zhi [Anhui provincial gazetteers: science and technology gazetteer]. Beijing: Fangzhi Publishing House, 1997, p. 575.
27.
For example, one article mentions that “the EHF mouse brain antigen slides were donated by Director Ni of the IMS.” See YangWSBaiXGZhangWB, et al. Liuxingxing chuxuere bingdu jing renti taipan chuizhi chuanbo ji zangqi dingwei de yanjiu [Vertical transmission of haemorrhagic fever virus through the human placenta and organ localization study]. In: Qingzhu Jianguo sanshiwu zhounian zhongguo renmin jiefangjun yixue keyan chengguo youxiu lunwenji[Celebrating the 35th anniversary of the founding of the People’s Republic of China: collection of outstanding papers on medical research achievements of the Chinese People's Liberation Army]. Beijing: People's Military Medical Press, 1986, p. 462.
28.
NiDSTanFLZhouN, et al. Liuxingxing chuxuere mianyixue yanjiu [Immunological research on epidemic haemorrhagic fever]. Liuxingxing chuxuere (16) [Epidemic haemorrhagic fever (16)]. Anhui Academy of Medical Sciences, Hefei, China.
29.
Department of Infectious Diseases of Huashan Hospital of First Shanghai Medical College. Huanlinxian'an zhiliao liuxingxing chuxuere de liaoxiao guancha he fabing jili de tantao [Observation of the efficacy of cyclophosphamide in treating epidemic haemorrhagic fever and discussion of its pathogenesis]. Bull Medical Res1977; 18: 4–6.
30.
NiDSTanFLZhouN, et al. Liuxingxing chuxuere mianyixue yanjiu [Immunological research on epidemic haemorrhagic fever]. Liuxingxing chuxuere (16) [Epidemic haemorrhagic fever (16)]. Anhui Academy of Medical Sciences, Hefei, China.
31.
LawrenceHS. The cellular transfer of cutaneous hypersensitivity to tuberculin in man. Proc Soc Exp Biol Med1949; 71: 516–522.
32.
MaciasAEGuani-GuerraE. Transfer factor: myths and facts. Arch Med Res2020; 51: 613–622.
33.
ChenSS. Zhengchangren zhuanyin yinzide linchuang yingyong [Clinical application of normal human transfer factor]. Chin J Internal Med1978; 1: 67–71.
34.
WangYF (ed). Shanghai di er yike daxue zhi [Gazetteers of Shanghai Second Medical University]. Shanghai: East China University of Science and Technology Press, 1997, p. 321.
35.
LiZL. Zhuanyi yinzi de yanjiu [Research on transfer factors]. In: LiZL (ed). Zhuanyi yinzi zai linchuang shang de yingyong [Clinical applications of transfer factors]. Wenzhou: Zhonghua Yixuehui Zhejiangsheng Wenzhoushi Fenhui, 1983, p. 3.
36.
LiZL. TF-P de yanzhi ji qi zai shouyi ji ren yi linchuang shang de yingyong baogao [preparation of TF-P and report on its application in veterinary and human clinical medicine]. Acta Acad Med Changwei 1984; 1: 9–13.
37.
Editorial Office for the Directory of Chinese Enterprises. A directory of Chinese enterprises. Vol 2. Beijing: Enterprise Management Publishing House, 1988, pp. 119–120.
38.
In 1995, the MOH issued the “Guidelines for the Management of Clinical Pharmacology Bases,” marking the formal launch of the clinical trial ethics review system. Prior to this, clinical trials in China were not subject to rigorous ethical scrutiny.
39.
YangYCQiuSHBiYD, et al.Texingxing zhuanyi yinzi zhiliao liuxingxing chuxuere de linchuang guancha. [Clinical observation on the treatment of epidemic haemorrhagic fever with specific transfer factor]. Anhui yixue [Anhui Med]1987; 8: 20–21.
40.
According to the National Science Foundation of China, 1986's Average amount of a single grant in biology was 25,700 Yuan. Se National Natural Science Foundation of China. guojia ziran kexue jijin xiangmu zhinan 1988 [National Natural Science Foundation of China Project guide 1988]. Beijing: China Science Publishing & Media, 1988, p. 10.
41.
HanJF. On the transformation of scientific research institutes. Contemporary China History Stud2023; 30, p. 58.
42.
Liuxingxing chuxuere teyixing zhuanyi yinzi de yanzhi he linchuang yingyong de yanjiu (Anhui sheng yiyao weisheng zhongdian keyan keti hetong 75-8601). [Research on the development and clinical application of a specific transfer factor for epidemic haemorrhagic fever (Contract No. 75-8601 for Key Scientific Research Project in Medicine and Health of Anhui Province)]. Liuxingxing chuxuere teyixing zhiliao yanjiu (18) [Research on specific treatment for epidemic haemorrhagic fever (18)]. Anhui Academy of Medical Sciences, Hefei, China.
43.
Anhui sheng yixue kexue yanjiusuo keyan keti xieyishu (86) ke 01 hao [Anhui Provincial Medical Science Research Institute Scientific Research Project Agreement (86) No. 01]. Liuxingxing chuxuere teyixing zhiliao yanjiu (18) [Research on specific treatment for epidemic haemorrhagic fever (18)]. Anhui Academy of Medical Sciences, Hefei, China.
44.
Guanyu liuxingxing chuxuere bingdu kangxueqing he teyixingxing zhuanyi yinzi hezuo yanjiu xieyishu [Memorandum of understanding for collaborative research on haemorrhagic fever virus antiserum and specific transfer factor]. Liuxingxing chuxuere texingxing zhiliao yanjiu (18) [Research on specific treatment for epidemic haemorrhagic fever (18)]. Anhui Academy of Medical Sciences, Hefei, China.
45.
BaiXFXuHFSunZJ, et al.A clinical double-blind trial of specific transfer factor on epidemic haemorrhagic fever. J Fourth Military Medical Univ1990; 11: 179–182.
46.
HuoBL (ed). Zhuanyi yinzi de yanjiu jinzhan: di si jie quanguo zhuanyi yinzi xueshu taolunhui wenji [Advances in transfer factor research: proceedings of the 4th National Symposium on Transfer Factor]. Beijing: China Science and Technology Press, 1990, pp. 47–50.
47.
Anhui Health Department. Tongyi “Liuxingxing chuxuere teyixing zhuanyi yinzi de yanzhi ji linchuang yingyong” keyan keti shenqing jianding de pifu [Approval of the application for the appraisal of the research project ‘Development and clinical application of specific transfer factors for epidemic haemorrhagic Fever’]. Liuxingxing chuxuere texingxing zhiliao yanjiu (18) [Research on specific treatment for epidemic haemorrhagic fever (18)]. Anhui Academy of Medical Sciences, Hefei, China.
48.
TangduhospitalNanjing Medical CollegeFuyang Institue of EHF, et al. A double-blind study of specific transfer therapy on epidemic haemorrhagic fever (EHF). In: HsiangCMZhengZZ HugginsJW (eds). Proceedings of International Symposium on Epidemic Haemorrhagic Fever (Haemorrhagic Fever with Renal Syndrome). Wuhan: Hubei Medical University Virus Research Center, 1989: 59.
49.
Anhui sheng kexue jishu jinbu jiang shenbaoshu. [Anhui Provincial Science and Technology Progress Award application form]. Liuxingxing chuxuere teyixing zhiliao yanjiu (18) [Research on specific treatment for epidemic haemorrhagic fever (18)]. Anhui Academy of Medical Sciences, Hefei, China.
50.
KimGB. The research network in Ho Wang Lee’s haemorrhagic fever investigation. Korean J Hist Sci2005; 27: 1–25. ShinM. Ho Wang Lee’s research of epidemic haemorrhagic fever and discovery of hantaan virus. Korean J Hist Sci2007; 29: 201–229.
51.
LaiLFarquharJ. Nationality medicines in China: institutional rationality and healing charisma. Comp Stud Soc Hist2015; 57: 381–406.
52.
LiYLYuCW (eds). Jiankang xiao guwen [Health advisor]. Zhengzhou: Henan Science and Technology Press, 1982, pp. 556–557.
53.
MaciasAEGuani-GuerraE. Transfer factor: myths and facts. Arch Med Res2020; 51, p. 620.
54.
According to the pharmacopoeia, the effect of TF therapy is “a bi-directional regulation of the body’s immune function, so that the body’s immune disorders can be corrected”. See Chinese Pharmacopoeia Commission. Zhonghua renmin gongheguo yaodian linchuang yongyao xuzhi 2015 [Clinical usage guidelines for the Pharmacopoeia of the People's Republic of China 2015]. Vol chemical grugs and biological products. Beijing: China Medical Science Press, 2017, p. 1126. See also DengYTianDYLiuEM, et al. Expert consensus on the rational use of immunomodulators for common respiratory diseases in children (2024 edition). Chin J Pract Pediatr2024; 39: 801–809.
55.
According to data released on the official website of the National Disease Control and Prevention Administration, the 2024 national summary of legally notifiable infectious diseases indicates that EHF resulted in 12 deaths (the latest annual summary of legally notifiable infectious disease statistics is current as of 2024). See https://www.ndcpa.gov.cn/jbkzzx/c100016/common/content/content_1998217472895258624.html (accessed 23 February 2026).
