In 18th century Europe, a most potent killer was ravaging entire populations. It had been claiming the lives of 400,000 victims a year. Those who survived its horrors were left disfigured or blinded. Those who did not internally bled to death. The destruction caused was so great, the dread so severe enough to merit its description as “The Speckled Monster”. But, this was no ordinary monster. The Speckled Monster was a silent monster, sweeping invisibly across countries and continents in successive waves and devouring victims by the hour. This monster was no other than smallpox, the deadliest of all killers, one that had killed more people in recorded history than all infectious diseases combined and all wars combined. From 1900 to 1980 alone, this fateful disease had been responsible for the deaths of up to 500 million people, only to be vanquished and eradicated by the power of science.

It is thought that smallpox first appeared 10,000 BC in Africa. Ancient Egyptian scrolls dating back as early as 3,000 BC tell of a disease exhibiting characteristics and symptoms very much like those that would be recognized of smallpox today. Mummified remains dating 1570 – 1085 BC carry pock marks indicative of smallpox. The skin and face of the mummified body of Pharaoh Ramses V, who died about 1140 BC, are scarred with a rash and lesions that bear witness to ravages brought about by smallpox. Sanskrits that correspond to this time period describe an outbreak of a characteristically similar pox disease in present-day India. It is thought that Egyptian merchants contributed to the spread of this disease to India. The Muslim conquest of Spain in the 7th century introduced the disease in Spain. The time period from the twelfth to fourteenth centuries saw intensive Crusade activity and movement of expeditions across Europe and the Middle East which further spread the disease across Europe. The Spaniard invasion of South America in the 15th century introduced smallpox epidemics that decimated the flourishing Aztec and Incan Empires of the time. By the 16th Century, smallpox was becoming a major killer. As much as 90 percent of the native American Indian populations were thought to have been wiped off by it. By the end of the 18th Century, the disease was killing 400,000 Europeans a year and had spread as far as Australia. Anywhere where populations grew sufficiently to sustain endemic transmissions, the Speckled Monster raged invincibly.

Smallpox is a member of the orthopoxvirus family, most of which cause zoonotic infections. It is thought that smallpox was accidentally transmitted to human hosts some 12,000 years ago when the disease jumped from domesticated cattle to humans. Smallpox is carried by two strains of the variola virus, Variola major and Variola minor. Variola minor is the less severe variant, historically responsible for a 1 percent mortality rate, as opposed to its Variola major counterpart that was, typically, responsible for a much greater mortality rate of 30 %. Variola minor is a milder form of smallpox, manifesting in a milder rash and a milder systemic reaction. Variola major, on the other hand, is a greater culprit, culminating, in the severest of cases, in hemorrhagic bleeding. Most frequently however, Variola major manifests in ordinary smallpox, typified by an pre-eruptive phase of malaise, fever, and headache followed subsequently, a few days later, by an eruptive phase of oropharyngeal macules that spread and evolve into the characteristic pustules that so define smallpox. Concomitant with the development of lesions is a maculopapular rash that first appears on the face, forearms, and hands, and then progressively develops throughout the body. Sweeping fluid and electrolyte loss resulting from these lesions, ultimately, leads to renal failure. Concomitant complications include massive skin loss, hypotension, eye infection, and secondary infections.

The contagious capacity of smallpox and the fact that it can be spread readily via the respiratory route reinforced a characteristically silent progression that saw the wiping out of villages in just a matter of days. Smallpox, indeed, remained unstoppable until the advent of the cowpox vaccine, developed by the English physician and scientist Edward Jenner in the late 1700s. At the time, it had been commonly known to English doctors that survivors of smallpox who had suffered a mild exposure of smallpox had lifelong immunity to the disease and did not develop it again. This knowledge ushered in attempts to perform variolations, where dried pus from the smallpox lesions of a recovering individual were introduced subcutaneously into the skin of a healthy individual. Such practices were of widespread use before Jenner. They usually produced mild complications but provided further immunity from infection. Dangerous complications were reported however, as were incidences of unintentionally transferred diseases like syphilis.

It wasn’t until 1796 that the next major advance against the Speckled Monster would be delivered. Edward Jenner had realised that milkmaids and dairy workers who had worked with cows and developed cowpox, a much milder form of smallpox and one that is far less dangerous, did not develop smallpox. Jenner began experimenting with this purported relationship between cowpox and smallpox and to test this hypothesis, he performed routine inoculations. He collected data from 28 cases, each of which represented instances where previously acquired cowpox resulted in protection against smallpox. Results seemed to confirm such a prediction.

In one particular instance in May 1796, a young milkmaid by the name of Sarah Nelms had visited Jenner in his office. Jenner noted the cowpox lesions on her hands and arms. This spurred Edward Jenner to carry out his crucial experiment, perhaps one that would be considered quite unethical by today’s standards. He extracted cowpox fluid from a sore on the milkmaid’s hand and, on May 14th 1796, injected it into an 8-year-old farm boy by the name of James Phipps. Six weeks later, Jenner deliberately injected the boy with fluid from a smallpox sore from one of his very ill patients and recorded: “No disease followed.”

Despite Jenner’s success, the news was met with doubt and opposition. Much of the outrage was evinced in regards to use of diseased bovine material and the idea seemed rather insane. Religious leaders condemned the practice as interfering with God’s plans and will. In 1796, Jenner submitted his experimental results for publication to the Royal Society. It was promptly rejected due to insufficient data. Jenner was further cautioned that he was “in variance with established knowledge” and that “he had better not promulgate such a wild idea if he valued his reputation.” This spurred Jenner to collect more data and inoculate several more children using this “arm-to-arm” method. Eventually, Jenner published his data at his own expense in a masterwork titled An Inquiry Into the Causes and Effects of the Variolae Vaccinae: A Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire, and Known by the Name of the Cow Pox. It described patients who were conferred immunity against smallpox and included a record of observations that provided robust evidence for Jenner’s hypothesis. Jenner named his new procedure vaccination from the Latin word “vacca” meaning cow.

As time went along, the opposition waned and Jenner’s techniques, like smallpox, sweeped across Europe and the Americans. The vaccination reached Virginia and caught Thomas Jefferson’s unwavering support. Jefferson wrote to Jenner to express his deep admiration:

“Sir,

I have received a copy of the evidence at large respecting the discovery of the vaccine inoculation which you have been pleased to send me, and for which I return you my thanks. Having been among the early converts, in this part of the globe, to its efficiency, I took an early part in recommending it to my countrymen. I avail myself of this occasion of rendering you a portion of the tribute of gratitude due to you from the whole human family. Medicine has never before produced any single improvement of such utility […] You have erased from the calendar of human afflictions one of its greatest. Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated.

Accept my fervent wishes for your health and happiness and assurances of the greatest respect and consideration”

In 1805, Napoleon Bonaparte vaccinated his entire army. Upon Jenner’s request, Napoleon immediately released English prisoners of wars, remarking that he could not “refuse anything to such a great benefactor of mankind.” In England, Jenner was celebrated with financial rewards and appointment as Physician Extraordinary to King George IV.

While the idea behind inoculations was already known before Jenner’s time, Jenner’s fundamental genius rests in his insights to recognise the cross-immunity between smallpox and cowpox and in his providing a thorough epidemiological and scientific basis behind his claims. We now know that the immunity conferred is due to antigenic cross-reactivity that allows anti-cowpox antibodies to bind to smallpox epitopes.

Jenner’s successful efforts to promote the idea of vaccination, in the face of enormous opposition, was his greatest achievement. As Francis Galton once famously remarked, in science, the credit usually goes to the person who convinces the world and not the person to whom the idea first occurs. And, indeed, thanks to Jenner, the world discovered vaccines. By the late 1900s, many countries had conquered smallpox and vaccinations were enforced globally. On May 8, 1980, the World Health Organization stunningly declared smallpox to have been entirely eradicated worldwide. The Speckled Monster was, now, no more than an ancient relic trapped in some laboratory vials.

Bibliography

Barquet N and Domingo P. 1997. Smallpox: The Triumph over the Most Terrible of the Ministers of Death. Ann Intern Med 127(8): 635–642.

Baxby D. Jenner’s Smallpox Vaccine: The Riddle of Vaccinia Virus and Its Origins. London: Heinneman’s Educational Books, 1981

Harding Rains AJ. Edward Jenner & Vaccination. London: Priory Press Ltd, 1974

Hopkins DR. Princes and Peasants. Smallpox in History. Chicago: University of Chicago Press, 1983

Moore JC. The History of the Smallpox. London: Longman, 1815