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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 2

Development of smallpox and variolation in study of variolation techniques, medical explanations, and dissemination in late Imperial China*

Period; key works Development of smallpox studies in TCM Contribution to the invention of variolation
The Wei, Jin, and Northern and Southern dynasties (3rd–6th centuries); Ge Hong’s handbook of prescriptions for emergencies (Zhouhou Beiji Fang) (21)
 Recognized the contagiousness of smallpox (shi xing bing). Texts inferred that lesion material might participate in transmission.
 Early recognition of contagion generated the idea that material from patients could induce disease in others, which was a conceptual precursor to deliberate inoculation.
Song dynasty (≈12th century); Qian Yi’s Key to Therapeutics of Children’s Diseases (Xiao’er Yao Zheng Zhi Jue) (22)
 Proposed congenital susceptibility (pathogenic qi contracted in utero) as part of smallpox etiology. This pathogenic qi originates from the mother's behaviors during pregnancy, such as indulging in greasy and sweet foods, being frequently depressed or angry, indulging in sexual desires, or having malignant diseases, including syphilis. The toxic fire generated from those factors is stored in the essence and blood. The fetus is affected by this toxin from the mother during fetal development, leading to diseases after birth.
 Laid the foundation for the etiologic theory of fetal toxin (tai du). Fetal toxin is an etiologic term in TCM.
Ming dynasty (≈15th–16th centuries); Wang Quan’s jade fragments on smallpox (Pian Yu Dou Zhen) and essential principles of smallpox (Dou Zhen Xin Fa) (23)
 Consolidated the belief that 1 attack implied durable protection. Elucidating the etiology and pathogenesis of smallpox according to the theories of fetal toxin and external pathogens. Seasonal pathogenic qi (Shi Qi) was considered contagious, and smallpox pustules were believed to spread through interpersonal transmission. Because fetal toxin was viewed as an intrinsic bodily factor, it was believed that everyone carried the risk of developing smallpox.
 Mapped historical categories to prevention, if disease confers durable protection; a milder, induced course might preempt severe natural disease, a rationale later invoked for variolation. It was also believed that a single infection could eliminate fetal toxin, rendering the person immune to future attacks. This led to the idea of inducing a mild, controlled infection through artificial means, thus, guiding the excretion of fetal toxin from the body and removing internal susceptibility and building immunity, rather than waiting for natural exposure.
Ming dynasty (≈15th–16th century); Wang Quan’s essential principles of smallpox (Dou Zhen Xin Fa) (23)
 It identified lifelong immunity after a single smallpox infection, frequently cited later to justify deliberate, milder smallpox induction.
Middle to late Ming to early Qing dynasties (15th–17th century); Zhu Chungu’s Conclusive theories on smallpox and rashes (Dou Zhen Ding Lun) (7) It articulated “While the external factor—the pathogenic qi—was beyond human control, the internal factor, fetal toxin, could be controlled through human intervention. Before exposure to the external virus, individuals could deliberately introduce inoculum into the body to expel fetal toxin.” With its relatively low virulence, this inoculum caused only a mild smallpox infection, safely and effectively expelling fetal toxin and thus preventing life-threatening disease. The synthesis of theory and practice provided internal coherence to variolation within TCM, enabling acceptance and widespread implementation.

*TCM, traditional Chinese medicine.

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1These first authors contributed equally to this article.

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