© 2002 Ardor Scribendi, Ltd

Yong Ming Li (2002) Inoculation against smallpox: Perspectives in the West and the West in regard to variolation. Dermatopathology: Practical and conceptual. 8(3), available on www.derm101.com

DIFFERENT VIEWS FROM THE EAST AND FROM THE WEST

Inoculation Against Smallpox: Perspectives in the West and the East in Regard to Variolation

Yong Ming Li, MD

Introduction

Smallpox (variola) was epidemic for thousands of years in both the East and the West, being responsible for millions of deaths throughout the world. The fight of man against this deadly disease continued until the eradication of it in 1978. For centuries, variolation, a technique by which a healthy individual is inoculated with pus taken from a patient with smallpox, was employed in both the East and the West for the purpose of inducing natural immunity against the disease, long before vaccination with cowpox was introduced by Edward Jenner in 1796.

The History of Variolation as It Is Told in the West

Inoculation against smallpox, although practiced for long in the Ottoman Empire, did not find acceptance in Europe until the eighteenth century. The first hint of that phenomena in the literature of the English language can be found in Peter Kennedy's work, published in London in the early seventeenth century, titled, "An Essay on External Remedies." There, Kennedy described a method for "giving or engrafting the small pox." This is what he wrote: "It [variolation] was practiced in the Peloponnesus (now called the Morea) and, at this present time, is very much used both in Turkey and Persia, where they give it in order to prevent its more dismal effects by the early knowledge of its coming, as also probably to prevent their being troubled with it a second time. This method of the Persians is to use the Pock and matter dried into powder, which they take inwardly; but the common way now used in Turkey, and more particularly at Constantinople, is thus: they first take a fresh and kindly Pock from some one ill of this distemper, and having made scarifications upon the forehead and legs, or extremities, the matter of the Pock is laid upon the foresaid incision, being bound on there for eight to ten days together; at the end of which time, the usual symptoms begin to appear, and the distemper comes forward as if naturally taken ill, though in a more kindly manner and not near the number of Pox."¹

Little attention was paid to the description of inoculation by Kennedy, but more interest was aroused in England when a volume of the Philosophical Transactions of the Royal Society for 1713–1716 contained two additional descriptions of the technique, one by Emanuel Timoni captioned, "An account, or history, of the procuring of the smallpox by incision, or inoculation; as it has for some time been practiced at Constantinople."²

Inoculation for smallpox came to be advocated by Lady Mary Wortley Montagu, the wife of the British Ambassador to Turkey, when, during her stay in Constantinople, she noted that "the smallpox, so fatal, and so general amongst us, is here entirely harmless, by the invention of ingrafting, which is the term they give it here." On March 18, 1718, Lady Mary Wortley Montagu had her 3-year-old son inoculated successfully by the physician at the British embassy in Constantinople, and in April, 1721, when the family returned to England had her five-year-old daughter inoculated there. The efforts of Lady Montugu at first were denounced harshly, but as a consequence of her influence, King George I permitted a pardon of condemned prisoners at Newgate Prison in return for their participation in experiments on inoculation. Eventually, the King allowed his own two granddaughters to be inoculated. The practice was accepted and became the fashion in Europe.³

In 1721, Jacob de Castro not only took cognizance of earlier methods of inoculation, but recommended the use of matter from a person inoculated artificially, rather than from one in which the disease had occurred naturally. He said that "there are few or none that make use of the Pus extracted from any who have this disease by transplantation, but this being of a milder disposition (I am very inclinable to believe) will be as proper as any other." This method of "arm-to-arm" inoculation, as it was called, became popular.³

During the smallpox epidemic in England between 1764 and 1765, nearly 20,000 persons were inoculated under the supervision of Daniel Sutton.

In the huge literature on inoculation in the eighteenth century, one of the most important items was the proposal by the Hungarian physician, Stepha Weszpremi (1723–1799), to inoculate in order to prevent plague (1755).²

Although recognized in Europe for centuries, smallpox was unknown in America until the arrival of Europeans. In April 1721, a ship that carried smallpox among its crew entered Boston harbor. Once the disease was identified for what it was, authorities in Boston quarantined the sick and the homes that housed persons infected, but the epidemic spread nevertheless. It was then that inoculation was introduced to America, in spite of obstinate opposition to it. The circumstances surrounding the introduction of variolation were related by James Thacher in his work, American Medical Biography (Boston, 1828, 2 vol.), as follows: "Dr. Cotton Mather, a learned divine in Boston, having observed in the Philosophical Transactions printed in London, an account of inoculation by Timoni and Pylarini in Turkey, communicated the information to several physicians in Boston, who treated the subject with contempt. He then recommended to his friend Dr. Zabdiel Boylston to adopt the practice. Accordingly with the little information which he could obtain from that publication, and in the face of most violent opposition, on the 27th day of June, 1721, Dr. Boylston inoculated first his only son about thirteen years of age, and two Negro servants, in which he was completely successful."⁴

A different version of the story holds that Mather, a clergyman from a distinguished family of clergyman, had heard about the efficacy of inoculation from his slave, Onesimus. Characterized by Mather as "pretty intelligent," Onesimus had informed his master that in Africa he, himself, had been inoculated against smallpox and had never caught the disease. Here is how Mather recorded the method as it was told to him by Onesimus: "People take Juice of Small-Pox; and cutty-skin, and putt in a Drop; then by'dn by a little sicky, sicky: then very few little things like Small-Pox; and no body dy of it; and no body have Small-Pox any more."⁵ In short, the contents of a pustule of an infected person who had a mild case of smallpox were inserted into the skin of a healthy person. Nine times out of ten the healthy person developed a mild case of the disease. Once the malady ran its course, the person was immune to smallpox.⁶

Mather was the foremost advocate of variolation in America, perhaps because the terrible disease had changed his own life so dramatically: two of his children and his wife succumbed to it. He called publicly on local physicians to inoculate Bostonians. William Douglass, the only physician in Boston with a European medical degree, opposed inoculation and argued that widespread inoculation could actually spread the disease. Some opponents argued that, "if God chose certain people to become sick, what human should dare to oppose God's will?" Dr. Zabdiel Boylston responded to the entreaties of Mather and did just what Onesimus advised. In subsequent months, Boylston inoculated over 150 persons. Other physicians participated as well, so that by the time the epidemic was over, almost 300 people had been inoculated. Only six persons inoculated died of smallpox, that is, 2% of all those infected. Of the 5,000 Bostonians infected by smallpox but who had not been inoculated, 18% died. Inoculation clearly worked.⁶ Eventually, Douglass himself came to appreciate the results of inoculation and became a lifelong advocate of it.

The History of Variolation as It Is Told in the East

As best as can be told by study of historical records, smallpox began to spread in China around the first century A.D. Ge Hong in Zhou Ho Bei Ji Fang (Pocket Formulas for Acute Diseases, 281–283 A.D.)⁷ provided details about epidemics and clinical manifestations of smallpox in China. He asserted that the disease was brought to China by prisoners of war. For that reason, the disease first was named Lu Chuang (Pox of the POW). Smallpox had long existed in China, but not until the fifteenth century, during the Tang and the Song Dynasty, did it become epidemic as a consequence of advances in transportation and of increases in travel. Many people, including several emperors, suffered from or died of smallpox. Because of the risk of dying from smallpox at a young age, when an emperor during Ming Dynasty chose his successor from among his sons, one of the factors in the selection was whether the son already had been infected by smallpox. There is an old saying in China that "a child delivered accounts for only half a baby; the another half depends on smallpox."

The application of a technique for immunization (variolation) against smallpox in China can be traced to the tenth century A.D. A story is told in Dou Zhen Ding Lun (Zhu Chun Gu, Diagnosis and Theory of Pox, 1713)⁸ that Prime Minister Wang Dan (955–1017), having lost several of his children to smallpox, was seeking desperately a preventive against the pestilence for his newborn son. He invited a physician for consultation from a remote region in the Er Mai Mountains of Shichuan and the monk suggested that the son, Wang Su, be inoculated with the matter of the pox. Wang Su lived to 67 years of age.

Between 1567 and 1572, in the Long Qing period, Ming Dynasty, the technique of variolation was practiced locally, having begun in Ning Guo Fu County and spread to all parts of the country. Most practitioners of inoculation were from Ning Guo (Yu Mao Kun, Ke Jin Jing Fu Ji Jie (Special Golden Mirror and Solutions), 1727).⁹ Yu Chang in Yu Yi Cao (Tales of Herbs, 1643)¹⁰ described examples of inoculation with smallpox performed by two brothers from the family Gu. Ten years later, as recorded in San Gang Shi Lue by Dong Han,¹¹ a doctor Zhang was known to practice inoculation with pox material and he did that for three generations. The method, based on his personal experience, was first to collect pox fluid from infected children and then store the fluid in a porcelain bottle underground for use later. In the performance of inoculation, the pox fluid was painted onto garments and children were then obliged to wear the infected clothing for a period of time. A mild form of the pox usually appeared on day 5 and reached its maximal development on day 10 (Yu Mao Kun, Ke Jing Jing Fu Ji Jie, Special Golden Mirror and Answers, 1727).⁹ .

In 1681, doctor Zhang Yan was put in charge of inoculation of smallpox for royal families and for other privileged individuals. He observed that among 7,000 to 8,000 people inoculated, only 20–30 suffered from signs and symptoms of smallpox (Zhang Yan, Dou Ke Xin Su, A New Book for Pox Diseases, 1714).¹² This was probably one of earliest "clinical trials" employed for demonstrating the efficacy of variolation.

By the end of seventeenth century, by virtue of extensive utilization of the technique of inoculation, the method became more refined. Zhang Lu, in Yi Tong (General Medicine, 1696),¹³ described several techniques of immunization against smallpox, including the nasal route using pox fluid or dried crusts, and topically by wearing garments saturated with pox fluid and suffused with pox crusts. During this period, techniques for variolation were in wide use in different parts of China.

The most complete description of techniques for variolation against smallpox was given in the official encyclopedia of medicine edited by Wu Qian et al. in his book, Yi Zhong Jin Jian-You Ke Zhong Dou Xin Fa Yao Zhi (Golden Mirror of Medicine, Principles for Inoculation of Pox to Children, 1742).¹⁴ A special volume was devoted to protocols of techniques and applications of inoculation for smallpox. A total of 18 topics on inoculation for smallpox were discussed in the Golden Mirror of Medicine. The four methods of inoculation that were taught in detail are as follows:

Inoculation by wearing garments painted with pox fluid
Nasal inoculation with pox fluid taken freshly from patients
Nasal inoculation with dried pox crust
Nasal inoculation with pox fluid diluted with water

The authors compared and contrasted the four techniques and provided indications and contraindications for them in regard to different manifestations of smallpox, as well as general information about how to store pox fluid. They concluded that of the four methods, water-dilated pox fluid is the best, dried pox crust is second, pox garment method does not work consistently, and fresh fluid inoculation is too dangerous to even attempt. In respect to the best method for storage of pox fluid, the authors proposed using a pristine new bottle and sealing the container well, advising that the bottle be placed in a clean, cool place.

After many years of practice and trials on thousands of individuals, the physicians made numerous important observations. As a consequence, the variolation technique against smallpox improved steadily. Doctor Zhu Yi Liang in Zhong Duo Xin Fa (Experience of Pox Inoculation)¹⁵ suggested that the best pox fluid for inoculation is the one that has been passed through several individuals. By doing so, the most infectious component in the fluid decreases in virulence and at the same time the potency of it increases. According to him, the best pox fluid is the one that has passed through seven generations of individuals, termed by him matured pox fluid. These observations and practices are entirely consistent with the modern concept of attenuation of live virus during preparation for vaccination, a concept that is lent evidence from clinical trials on humans.

The Links Between the Stories Told in the West and the East

The effectiveness of the technique of variolation for prevention of smallpox spread far beyond the borders of China by virtue of increase in exchanges between nations and people.^16,17

For more than 2,000 years, people have been crossing the formidable mountains that lie between the Western world and China. As early as 200 B.C., silk, gemstones, precious spices, and medicines were transported along the route from Xi An, China to Constantinople, Turkey and, in reverse, from the West to China. Marco Polo is the best-known early traveler of this lengthy way. It was in the 1870s that a German, Ferdinand von Richthofen, named the route the "Silk Road."

As a result of increased communication between West and East, diseases such as smallpox, measles, and other infections became epidemic along the Silk Road. Exchanges of medicines were common as merchant-travelers. It is believed that the technique of variolation came to Turkey from China by way of this path and, in time became a common practice among the Turks for preventing smallpox. It was Lady Montagu who brought the technique from Turkey to Great Britain and thus promoted application of it throughout Europe.

According to an official record of the Chinese government, a Russian physician came to Peking (Beijing) in 1688 and received formal training there in the inoculation technique for smallpox. In 1744, Li Renshang, from Hang Zhou, China, went to Japan and there introduced the techniques of pox inoculation to two monks. Soon after that the Golden Mirror of Medicine, an encyclopedia of Chinese medicine with detailed descriptions of pox inoculation, became available in Japan.¹⁸ In the same period, the technique of inoculation also was introduced to Korea and other parts of Asia.¹⁹

In 1805, the method of inoculation with cowpox (vaccination) was brought to China by Portuguese merchants from Macao.¹⁸ Because of its safety and convenience, vaccination replaced variolation, and the new method gained acceptance quickly in China. Vaccination was practiced throughout China until the time that smallpox was eradicated.

Conclusion

The story of variolation just told can be found in English and Chinese in literature published in the West and in China. For hundreds of years the history of variolation was described differently in these two worlds; West and East never met. I have attempted to rectify that here.

Dr. Li undertook this work during his fellowship at the Ackerman Academy of Dermatopathology in New York City.

References

1. Crookshank EM. History and Pathology of Vaccination. 1889;(2)1:4.

2. Mettler CC, Mettler FA (eds.). History of Medicine, New York: The Blakiston Company, 1947;419–21.

3. Garrison FJ. An Introduction to the History of Medicine, London: WB Saunders Co. 1966;373.

4. Pusey WA. The History of Dermatology. Charles C Homas, 1933.

5. Mather C. The Angel of Bethesda, An Essay Upon the Common Maladies of Mankind. Edited by Gordon W. Jones. Barre, Massachusetts: American Antiquarian Society and Barre Publishers, 1972.

6. The Inoculation Controversy (1600–1754). www.galenet.com/servlet/HistRC/hits.

7. Ge Hong, Zhou Ho Bei Ji Fang, Pocket Formulas for Acute Diseases, 281–283 A.D.

8. Zhu Chun Gu, Dou Zhen Ding Lun, Diagnosis and Theory of Pox, 1713.

9. Yu Mao Kun, Ke Jing Jing Fu Ji Jie, Special Golden Mirror and Answers, 1727.

10. Yu Chang, Yu Yi Cao, Tales of Herbs, 1643.

11. Dong Han, San Gang Shi Lue,Principles of Three Gang, 1653.

12. Zhang Yan, Dou Ke Xin Su, A New Book for Pox Diseases, 1714.

13. Zhang Lu, Yi Tong, General Medicine, 1695.

14. Wu Qian, et al., Yi Zhong Jin Jian-You Ke Zhong Dou Xin Fa Yao Zhi [???–????], Golden Mirror of Medicine: Principles for Inoculation of Pox to Children, 1742.

15. Zhu Yi Liang, Zhong Duo Xin FaExperience of Pox Inoculation.

16. Xie S, Zhang D. Spread of Chinese variolation art to the Western world and its influece. Zhonghuan Yi Shi Za Zhi 2000 Jul;30(3):133–7.

17. Zhu BZ. History of the vaccination of human pox. Zhong Xi Yi Jie He Za Zhi 1982;Oct 2(4):247–8.

18. Brief History of Variolation in China: http://www.huatuo.org/history/rendou.htm.

19. Chun, CH. The history of small pox prevention in Korea. Uisahak. 1993:2(2):122–5.