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Volume 32, Number 10—October 2026

Historical Review

Variolation Techniques, Medical Explanations, and Dissemination in Late Imperial China

Linyu Guan1, Shenjia Gu1, Yunhai Pan, Lance E. Rodewald, and Chuanxi FuComments to Author 
Author affiliation: Zhejiang Chinese Medical University, Hangzhou, China (L. Guan, S. Gu, Y. Pan, C. Fu); Chinese Center for Disease Control and Prevention, Beijing, China (L.E. Rodewald)

Main Article

Table 3

Comparison of cognitive theories on smallpox between TCM and Ayurveda in study of variolation techniques, medical explanations, and dissemination in late Imperial China*

Category Country tradition
TCM, China Ayurveda, India
Etiology
 Fetal toxin and external pathogenic factors: fetal toxin is congenital and latent in the body; Shi Qi refers to pathogenic qi generated by abnormal climate, originating from nature.
 Dietary disorders, including consumption of spicy, sour, penetrating, heating, burning (during digestion), dry, and alkaline foods and beverages; indigestion; overeating; sun exposure; abnormal climate. In 1767, Holwell recorded that direct cause was the mortal part of each human and animal form; indirect cause was multitudes of imperceptible animalculae floating in the atmosphere (25).
Pathogenesis
 Shi Qi invades the body, triggers the inherent fetal toxin within, causes the fetal toxin to be expelled from inside to outside, and eventually manifests as pox eruptions on the skin.
Dietary disorders, sun exposure, and abnormal climate cause an imbalance in ≥1 of the 3 vital life energies—Vata (wind), Pitta (bile), and Kapha (phlegm)—which in turn leads to damage to the blood, muscles, and bones, as well as the formation of blisters (smallpox) on the skin, accompanied by fever.
Prevention and treatment
 Treatment is divided into 6 stages: febrile, eruption, swelling, pustulation, crusting, and desquamation stages, with syndrome differentiation and treatment applied respectively. For each stage, the main focus is on differentiating the conditions of qi and blood (deficiency or excess), cold, heat, and toxic fire; corresponding prescriptions are used for replenishing qi and blood, warming the middle and dispelling cold, clearing heat and detoxifying, supporting the interior, and expelling toxins. TCM treatment of smallpox emphasizes protecting and replenishing qi and blood, believing that fetal toxin relies on qi and blood for expulsion. Prevention is variolation.
 Treatment involves first fasting and inducing emesis with appropriate use of purgation. Then, according to the type of smallpox (i.e., which one or more of the vital energies are imbalanced), corresponding herbal decoctions are administered, and topical medications are applied to the skin to relieve blisters, burning sensations, and pain. The medications used are traditional natural medicines used in India. Prevention is variolation.
Inoculum
 Smallpox scab (serial passaging, mature inoculum)
 Smallpox pus
Inoculation site
 Intranasal (mucosal)
 Skin on the forearms, fingers, or forehead
Inoculation procedure The technique evolved sequentially from the smallpox garment/blanket method to the lymph method, and the scab method was ultimately recognized as the optimal protocol. The core operation consisted of skin puncture followed by inoculation with smallpox pus.

*Shi Qi, seasonal pathogenic qi; TCM, traditional Chinese medicine.

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References
  1. World Health Organization. Smallpox and its eradication. 1988 [cited 2026 Apr 21]. https://iris.who.int/items/ba4ab312-1c43-4304-8235-969979499717
  2. Shchelkunova  GA, Shchelkunov  SN. Smallpox, monkeypox, and other human orthopoxvirus infections. Viruses. 2022;15:103 .DOIPubMedGoogle Scholar
  3. Parrino  J, Graham  BS. Smallpox vaccines: past, present, and future. J Allergy Clin Immunol. 2006;118:1320–6 .DOIPubMedGoogle Scholar
  4. Dinc  G, Ulman  YI. The introduction of variolation “à la Turca” to the West by Lady Mary Montagu and Turkey’s contribution to this. Vaccine. 2007;25:4261–5 .DOIPubMedGoogle Scholar
  5. Theves  G. Smallpox: an historical review [in German]. Bull Soc Sci Med Grand Duche Luxemb. 1997;134:31–51.PubMedGoogle Scholar
  6. Ma  BY. History of Chinese medical culture, vol. 1 [in Chinese; Zhongguo Yixue Wenhua Shi (中国医学文化史)]. Shanghai: Shanghai People’s Publishing House; 2010. p. 423–533.
  7. Zhu  CG. Conclusive theories on smallpox and rashes [in Chinese; Dou Zhen Ding Lun (痘疹定论)]. Block-printed edition; 1852 [cited 2026 Apr 21]. https://dpul.princeton.edu/eastasian/catalog/m613n1179
  8. Yu  MK. Annotations on the golden mirror ode to smallpox, vol 2 [in Chinese; Dou Ke Jin Jing Fu Ji Jie (痘科金镜赋集解)]. Guangxu Emperor reign, block-printed edition; p 25 [cited 2026 Apr 21]. https://www.shidianguji.com/book/CADAL02035678/chapter/1l7lgzw1rdvl2
  9. Zhang  Y. New treatise on variolation, vol 3 [in Chinese; Zhong Dou Xin Shu (种痘新书)]. Block-printed edition, 1741 [cited 2026 Apr 21]. https://dpul.princeton.edu/eastasian/catalog/td96k515v
  10. Fan  XZ. History of Chinese preventive medical thought [in Chinese; Zhongguo Yufang Yixue Sixiang Shi (中国预防医学思想史)]. Shanghai: East China Medical Life Press; 1953. p. 81–144.
  11. Leung  AKC. “Variolation” and vaccination in late Imperial China, ca 1570–1911. In: Plotkin SA, editor. History of vaccine development. New York: Springer; 2011. p. 5–12.
  12. Ma  BY, Gao  X, Hong  ZL. History of Sino-foreign medical cultural exchange [in Chinese; Zhongwai Yixue Wenhua Jiaoliu Shi (中外医学文化交流史)]. Shanghai: Wenhui Press; 1993. p. 613.
  13. Needham  J. China and the origins of immunology. East Horiz. 1980;19:6–12.PubMedGoogle Scholar
  14. Sugandi  R. Knowledge Ottoman Turkish medicine: from methods immunization traditional to pioneer world vaccine [cited 2026 Apr 21]. https://pdfs.semanticscholar.org/2543/f626141eda58a870e47e6152d4e5bc1f0057.pdf
  15. Plotkin  SA, Orenstein  WA, Offit  PA, Edwards  KM. Plotkin’s vaccines, 7th edition. Luo FJ, Li CG, Yang XM, translators. Beijing: People’s Medical Publishing House; 2023.
  16. Zhang  L. Zhang’s Comprehensive Medicine [in Chinese; Zhang Shi Yi Tong (张氏医通)]. Li JF, Jian Y, annotators. Beijing: China Traditional Chinese Medicine Press; 1995. p. 329–30.
  17. Wu  Q. The Golden Mirror of Medicine [in Chinese; Yi Zong Jin Jian (医宗金鉴)]. An YZ, Yuan H, editors. Beijing: China Traditional Chinese Medicine Press; 1994. p. 691–92.
  18. Fu  CX. Vaccines and immunization. Beijing: People’s Medical Publishing House; 2020.
  19. Noble  J Jr, Rich  JA. Transmission of smallpox by contact and by aerosol routes in Macaca virus. Bull World Health Organ. 1969;40:279–86.PubMedGoogle Scholar
  20. Zhu  YL. Essentials of variolation [in Chinese; Zhong Dou Xin Fa (种痘心法)]. In: Wang YW, editor. Cong Shu Ji Cheng Chu Bian. Shanghai: Commercial Press; 1936. p. 5–6.
  21. Ge  H. Transcendent Master Ge’s emergency-preparedness recipes to keep close at hand, vol 2 [in Chinese; Ge Xian Weng Zhou Hou Bei Ji Fang (葛仙翁肘后备急方)]. Li Shi block-printed edition. Beijing: National Library of China collection; 1574. p. 18.
  22. Qian  Y. Key to the therapeutics of children’s diseases [in Chinese; Xiao Er Yao Zheng Zhi Jue (小儿药证直诀). Yan XZ, compiler; Guo JS, collator. Beijing: People’s Medical Publishing House; 2017.
  23. Wan  Q. Complete medical works of Wan Mizhai [in Chinese; Wan Mi Zhai Yi Xue Quan Shu (万密斋医学全书)]. Fu PF, Yao CS, Wang XP, editors. Beijing: China Traditional Chinese Medicine Press; 1999.
  24. Hopkins  DR. The great killer: smallpox in history. Shen YM, Jiang GN, translators. Shanghai: Shanghai People’s Publishing House; 2005.
  25. Naraindas  H. Preparing for the pox: a theory of smallpox in Bengal and Britain. Asian J Soc Sci. 2003;31:304–39. DOIGoogle Scholar
  26. Nicholas  RW. The goddess Sitala and epidemic smallpox in Bengal. J Asian Stud. 1981;41:21–45.PubMedGoogle Scholar
  27. Fitchett  JR, Heymann  DL. Smallpox vaccination and opposition by anti-vaccination societies in 19th century Britain [cited 2026 Apr 21]. https://www.healthchoicevt.com/wp-content/uploads/2016/01/E17.pdf
  28. Maty  M. XVII. A short account of the manner of inoculating the small pox, on the Coast of Barbary, and at Bengal, in the East Indies, extracted from a memoir written in Dutch, by the Reverend Mr. Chais, at the Hague. Philos Trans. 1768;58:128–31. DOIGoogle Scholar
  29. Ainslie  W III. Observations respecting the small-pox and inoculation in eastern countries; with some account of the introduction of vaccination into India. Transactions of the Royal Asiatic Society of Great Britain and Ireland. 1830;2:52–73. DOIGoogle Scholar
  30. Bhāramiśra. Bhāvaprakāśa. Murthy KRS, translator. Varanasi: Chowkhamba Krishnadas Academy; 2008. p. 632–35.

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1These first authors contributed equally to this article.

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