In 1976, English physician Edward Jenner used fluid from a cowpox lesion and scratched it into the skin of an 8-year-old boy. Today, vaccinations achieve the same end goal as this crude procedure—protection (immunity) against a virus. With COVID-19 vaccines headlining every newspaper, pervading every conversation, and prompting many questions, I wanted to uncover the historic origins of vaccines. After all, to navigate the present pandemic, we must heed the lessons of history.
SmallPox: The "Speckled Monster" And The Origin of Vaccine Development
Approximately 300 million people lost their lives to smallpox in the 20th century.1 However, the basis of vaccinations all started with the destruction wreaked by smallpox during the 18th century.2 You may have heard of smallpox; however, because of its eradication decades ago, it’s unfamiliar to most of us. So what is smallpox exactly? Smallpox was a devastating disease caused by the variola virus that presented as pus-filled blisters and a high fever which ultimately crippled the immune system of its victims, and in some cases, caused blindness. Typically, people contract the virus via inhalation. It begins in the oral and respiratory membrane lining and ultimately travels to the lymph nodes where the virus will then begin to replicate. The virus will move into the spleen and bone marrow through the bloodstream where it will continue to make copies of itself. Within 13-17 days, lesions will become visible on the skin.
During the 18th century in Europe, 400,000 people died annually with a fatality rate of between 20% to 60%, where almost all survivors were left with disfiguring scars.2 Though smallpox ravaged nations during the 18th century, the very first evidence of smallpox skin lesions can be traced back to mummified remains of the 18th Egyptian dynasty (1550 to 1292 BC).3 That being said, it was not until the 4th century AD that written descriptions of smallpox appeared in China, and later in the 10th century in southwestern Asia.4
Variolation: Ancient Civilizations and Their Fight Against Smallpox
The notion of conferring immunity based on exposure to viral material (what is referred to as “antigens” in scientific literature) is far from new. Variolation, a name taken from the virus that causes smallpox (variola virus), is the deliberate inoculation (or exposure) of a “healthy” person to the smallpox virus 5. Dating back to as far as the 10th century in China, variolation involved using the dried crusts from smallpox lesions to induce immunity by either inhalation of the crushed lesions, or insertion into minor cuts.6 Typically, a mild case of smallpox would develop and it was believed to confer lifelong immunity. While there was a 2-3% chance of death subsequent to variolation, relative to the 20-30% death rate of natural smallpox, the odds made it worthwhile.7
The Spread of Variolation in The New World
In 1714, a letter written by Dr. Emanuel Timonius, a renowned fellow of the Royal Society at London who was situated at Constantinople (present day Istanbul), was circulated around Europe and read to the Royal Society by John Woodward.7 It contained his observations of a “sort of inoculation” with smallpox that had been conducted for about 40 years among Turks and others at Constantinople. He described thousands of inoculated patients who experienced mild symptoms, no death, and perhaps most importantly, the absence of severe facial scarring.8
This letter elicited responses and reactions from ministers around the world who became increasingly aware of the practice of variolation to combat smallpox.7 Variolation, in essence, was the initial crude attempt at immunization. Lady Mary Wortley Montague, the wife of a British diplomat at Constantinople, became intrigued with the practice after learning that it was conducted widely in Turkey and was an effective means of preventing smallpox.7 After contracting smallpox herself and losing her 20-year old brother to the deadly virus, she became determined to prevent her children from living the same fate.2 She ordered Charles Maitland, the embassy surgeon to perform the inoculation procedure on her daughter. This prompted intense interest in the practice among aristocratic and common people in England.2
In many cases, the procedure was conducted by purchasing scabs or pus from an individual suffering from natural smallpox, and subsequently puncturing the skin with a needle contaminated with smallpox. In other cases, smallpox scabs were held in the hands of children.7 These “patients” agreed that they had indeed contracted a mild smallpox infection, only to never experience an infection a second time.7
The World's First Vaccination
Edward Jenner, an English physician and scientist, developed a keen interest in the protective effects of cowpox during an apprenticeship in his mid-teens.2 For years, Jenner heard tales that dairymaids developed immunity for smallpox after contracting cowpox. After extensive deliberation, Jenner concluded that not only could cowpox protect against smallpox, but cowpox could also be transmitted from person to person as a means of deliberate protection.2
In May 1796, in order to validate this hypothesis, Jenner conducted an experiment in which he used fresh cowpox lesions from the hand of a young dairymaid to inoculate an 8-year-old boy named James Phipps. After experiencing a minor fever and loss of appetite, the young boy recovered days later. In July 1796, Jenner inoculated James with smallpox lesions and no disease developed.2 Jenner concluded that protection was complete and proceeded to send a paper to the Royal Society detailing his findings. Though his paper was rejected, he continued to gather additional cases to substantiate his initial experiment and privately published his findings in a booklet entitled, “An Inquiry into the Causes and Effects of the Vario- lae Vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire and Known by the Name of Cow Pox”.10 Jenner devised a name for this procedure: “vaccination” – stemming from the Latin word for cow (‘vacca’), and cowpox (‘vaccinia’).
Variolation vs. Vaccination
Vaccination entailed the use of matter from the milder cowpox virus which conferred the same immunities. As cowpox was a milder disease, this procedure was deemed as much safer than variolation which used viral material from smallpox patients. Despite much controversy surrounding Jenner’s findings, vaccination spread rapidly in England. By 1800, it had also become common practice in most European countries. Slowly, vaccination replaced variolation and by 1840 variolation became prohibited in England.2
The Eradication of Smallpox
During the late 19th century, the mortality rate from smallpox had indeed declined; however, the disease was still not under control and many countries were still being ravaged by smallpox.2 It was realized that vaccination did not bestow lifelong immunity. In other words, revaccination would be required. In 1967, a global campaign was launched by the World Health Organization (WHO) to eradicate smallpox.2 Thirteen years later, on May 8, 1980, the WHO formally announced that smallpox had been eradicated.
“The world and all its people have won freedom from smallpox, which was the most devastating disease sweeping in epidemic form through many countries since earliest times, leaving death, blindness and disfigurement in its wake.”10
Jenner’s relentless work represented the first scientific attempt to manage infectious disease through intentional usage of vaccination. While history indicates he was not the first to discover vaccination, he was the first to conduct extensive scientific investigation and establish scientific standing for the procedure.2 His devotion to the research on vaccination forever changed the practice of modern medicine.
1. Flight, C., 2011. Smallpox: Eradicating The Scourge. [online] Bbc.co.uk. Available at:
2. Riedel, S., 2005. Edward Jenner and the History of Smallpox and Vaccination. Baylor University Medical Center Proceedings, [online] 18(1), pp.21-25. Available at: .
3. Ruffer, M. and Ferguson, A., 1911. Note on an eruption resembling that of variola in the skin of a mummy of the twentieth dynasty (1200-1100B.C.). The Journal of Pathology and Bacteriology, 15(1), pp.1-3.
4. Spaulding, W., 1984. Donald R. Hopkins, Princes and Peasants: Smallpox in History (Chicago: University of Chicago Press, 1983)Donald R. Hopkins, Princes and Peasants: Smallpox in History (Chicago: University of Chicago Press, 1983), 380 pp., $25.00. Canadian Bulletin of Medical History, 1(1), pp.132-134.
5. 2002. Smallpox: A Great And Terrible Scourge. [online] Available at: .
6. Centers for Disease Control & Prevention. 2016. History Of Smallpox | Smallpox | CDC. [online] Available at: .
7. Boylston, A., 2012. The origins of inoculation. Journal of the Royal Society of Medicine, [online] 105(7), pp.309-313. Available at: .
8. Timonius, E., 1714. V. An account, or history, of the procuring the smallpox by incision, or inoculation; as it has for some time been practised at Constantinople. Philosophical Transactions of the Royal Society of London, [online] 29(339), pp.72-82. Available at: .
9. Winkelstein, W., 1992. Not Just a Country Doctor: Edward Jenner, Scientist. Epidemiologic Reviews, [online] 14(1), pp.1-15. Available at: .
10. 2021. The Achievement Of Global Eradication Of Smallpox : Final Report Of The Global Commission For The Certification Of Smallpox Eradication, Geneva, December 1979. [online] Geneva: World Health Organization, p.11. Available at: .
