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The History of Variolation


René F. Najera, DrPH

June 5, 2021

There was not much in the way of medical technology in the thousands of years of human history before vaccines. Edward Jenner developed the first vaccine in 1796. The first antibiotics were not developed until sulfa drugs and penicillin were discovered in the 1920s and 1930s. That is not to say that there was no medical theory and practice.

Before vaccines, epidemics were contained using quarantines, where ship passengers and cargo would be held off a port for a predetermined number of days to make sure anyone or anything carrying disease on board would either heal from the disease or die. If no one became ill after the quarantine period, they were deemed to be free of disease. The exact number of days was calculated based on observations of epidemics. From watching when someone was exposed to when someone showed symptoms of the disease, scientists advised governments on how many days to hold off those ships.

The earliest recorded guidance on disease control comes from Mosaic Law (the Law of Moses). Written in the first five books of the Hebrew Bible, the law gives instructions on how to deal with people infected with leprosy (now called Hansen’s disease) and venereal diseases. In Greece, Thucydides wrote about an epidemic that occurred in Athens in 429 BCE. The epidemic killed as many as a quarter of the residents of Athens. , even catching the disease himself. (The actual disease cause or what the disease was is still debated today.) Other physicians in ancient times, like Galen or Sushruta, theorized about disease transmission and prevention, coming close to being correct on the actual causes of infectious disease but unable to prove their theories without microscopes and modern laboratories.

The exact origins of variolation (also known as “inoculation”) . However, it is agreed that the practice started somewhere in Asia, in either China or India. (It is possible that it started in both places at around the same time.) In China, scabs from smallpox pustules would be dried in the sun and then inhaled by people seeking to be inoculated. The drying of the scabs would weaken the virus -- or make less of it viable -- and the inoculated person would (hopefully) not develop the full-blown symptoms of smallpox. In India, the method was similar to what would to the Middle East, North Africa and eventually Europe. That method involved lancing the pustule of someone recovering from smallpox and then using that same lance to transfer some of the pustule material (pus) into the arm of a healthy person.

Either method had to be practiced by someone with much experience in the procedure. . The minor form caused death in about 1% of those who were infected, and the major form caused death in about 30% of those who were infected. (Some estimates put the death rate in some epidemics if the population hit by the epidemic was especially susceptible.) As a result, a physician performing the variolation procedure had to recognize that the donor had variola minor, and that they were recovering from the disease, making the virus in the pustules less viable. When done wrong, variolation could actually trigger rather large epidemics, .

In 1706, . The congregation would go on to “gift” Onesimus to Reverend Cotton Mather. The reverend asked Onesimus one day about the scar Onesimus had on his arm. Onesimus explained that he and others had received smallpox inoculations in order to be safe from the disease. Upon hearing this, Rev. Mather consulted with a local physician by the name of Zabdiel Boylston, and Boylston consulted with colleagues. They arrived at the conclusion that variolation was worth trying, especially since Boston was a big trading harbor and Massachusetts suffered periodic smallpox epidemics when ships arrived carrying infected people. When smallpox arrived again in 1721, Mather and Boylston moved quickly to inoculate their family and servants. At the end of the epidemic, 14% of those who contracted smallpox “the natural way” had died. Of those who were inoculated, 2% died.

In 1717, traveled to the Ottoman Empire (modern day Turkey) along with her husband -- who was the British Ambassador to the Empire -- and her son, Edward. Upon hearing about the variolation procedure and its success in preventing smallpox, Lady Mary asked to observe the procedure, writing home about it in . Having caught smallpox herself two years earlier -- and losing her brother two years before that -- Lady Mary wished to spare Edward the experience of the disease. In the end, the variolation worked, and Edward recovered from mild symptoms of smallpox and became immune. In 1721, when smallpox yet again hit England, Lady Mary had her daughter inoculated. The event was well publicized and attracted the attention of the public. Lady Mary influenced the Princess of Wales to inoculate her daughters in 1722. From then on, inoculation would be practiced increasingly in European countries.

In 1768, continued her expansion of healthcare services in the Russian Empire by first and then inoculating her family. She would then go on to order that inoculation be practiced throughout the empire, resulting in over two million people receiving the procedure.

Around the same time that Catherine The Great was inoculating her subjects, a physician was trying to convince the people of Norfolk, Virginia, to adopt the procedure and prevent smallpox from decimating the community on a periodic basis. Like Boston, Norfolk was a port city and subject to arrivals of smallpox on trading vessels. Dr. Archibald Campbell hired Dr. John Dalgleish to perform inoculations on families in Norfolk. Not only that, but Dr. Dalgleish published articles supporting the practice. On June 27, a mob attacked Dr. Campbell’s home, where he was attempting to inoculate a group of people. . That same year, with Thomas Jefferson as a prosecutor, some of the people who attacked Dr. Campbell’s home were tried with only a few found guilty. 

In 1776, the American Revolutionary War was in full swing and General George Washington noticed that British troops were bringing smallpox with them wherever they went. After , partially due to smallpox, Washington realized that his troops needed to be inoculated and thus protected from smallpox. However, he also did not want newly inoculated troops to be laid out with the mild form of the disease for up to a month. As a result, his plan became to have new recruits inoculated () .

By the time Edward Jenner discovered vaccination with cowpox to prevent smallpox in 1796, variolation had been more widely accepted than ever. Yes, there were still detractors, but the practice had been refined in Europe to such a degree that it became an acceptable risk to governments to inoculate their troops and citizens. It was a risk because inoculation was still being done with the smallpox virus itself and not some animal analogue -- like cowpox -- that would be less dangerous. As word of Jenner’s vaccine and its safety and effectiveness spread, governments switched over to vaccination, with . As countries outlawed variolation, they codified requirements for vaccination. However, it would not be until the from 1966 to 1980 that the last remaining variolation programs were ended in Afghanistan and Pakistan.


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