Is smallpox set for a comeback?

Until very recently, the pantheons of the world’s religions swelled with gods and divine beings to ward off calamities. And none loomed so large as smallpox. From the inky beginnings of civilization, the disfiguring disease slowly spread over the entire Eurasian continent and North Africa. In the last millennium, smallpox alone has caused 10 percent of all human deaths, including half a billion in the 20th century.

In China, the goddess T’ou-Shen Niang-Niang was feared; her capricious whim could disfigure or kill. She especially loved a pretty face, and during her festival nights, children would wear ugly masks to bed in hopes of fooling her. In India, Shitala Mata not only caused smallpox but was also its healer, using cool food and drink dyed red. This association with the color red would spread throughout the world. And erythrotherapy, as it was later known, was the subject of randomized controlled trials in the early 20th century. In Western Africa, the Yoruba worshipped Shapona, who would express his displeasure with outbreaks of smallpox. In Europe, St. Nicaise, the bishop of Rheims, recovered from the disease just as the invading Huns fell ill. They managed to conquer anyway, and beheaded the saint. From thereafter, his prayer could cure the disease, with the implicit threat of also being able to spread it to your enemies. And when the Europeans did just that to the New World, sometimes intentionally, new gods took root in a land previously without smallpox, like Obaluaye “the King of the Earth.” His worshippers would double over in their dancing, mimicking the pain of its sufferers.

But the gods sowed the seeds of their own undoing. The ancients had noticed long ago that those who were pockmarked could never again be infected. In China, it was noted that those were infected from a cut in their arm or through their mucous membranes would suffer a far milder version of the disease and still be immune. By the 10th century, the cult of T’ou-Shen Niang-Niang was performing secret rituals where smallpox scabs were ground up and inhaled to protect children. In India as well, a needle covered with smallpox pus would be introduced into the skin to cause a local reaction. The modern word for this is variolation to differentiate it from vaccination, though at the time physicians used horticultural terms like transplanting or engrafting. By the 18th century, the colonial British had taken note. Only six years after variolation was introduced at the Royal Society in London, the royal princesses had the procedure, and by 1746 the London Smallpox and Inoculation Hospital offered free variolation to all. Variolation never caught on in a larger scale outside of British territory. The death rate was up to two percent, and this was a live virus fully capable of causing an outbreak. In any event, by the 1790s, the British had drawn up plans to variolate the entire population of the British Isles.

The plan never came to fruition because of Edward Jenner and the invention of vaccination. Starting in the 1760s, a series of physicians in England noted that milkmaids were not pockmarked, and that they would not take to variolation — they would not form skin lesions when inoculated with smallpox. These doctors also correctly presumed this was due to cowpox, a similar disease that only caused mild symptoms in humans. Edward Jenner took these observations and sampled the pus from the cowpox of Sarah Nelmes, a local milkmaid. He then used this pus to inoculate his eight-year-old neighbor James Phipps. Six weeks later, he performed variolation on Phipps, inoculating a smallpox-infected needle into the boy. And just like the milkmaids, he would not respond —he too was immune to the disease. Jenner called this new process vaccination, from the Latin root “vacca,” meaning cow. The cow in question, by the way, was named Blossom, and her hide and horns are preserved to this day.

Even in 1796, Jenner realized that his new vaccine would give humanity a way to end smallpox forever. And in the latter half of the 20th century, as the World Health Organization set about to finally end smallpox, its field workers ran into the disease’s last bastions of defense — the gods themselves. In West Africa and rural India, the worshippers of Shapona and Shitala Mata did what they could to disrupt the vaccination programs, convinced that it would displease their gods and lead to greater outbreaks. In China as well, religious adherence to variolation delayed adoption of universal vaccination. But the gods could only delay medicine, and in 1977 the last natural case was recorded in Somalia, and by 1979 — 183 years after Jenner’s discovery — the WHO finally declared smallpox eliminated.

The eradication of smallpox is one of the greatest moments in human history. But great threats still remain. We thought there were only two known samples of smallpox remaining in the world, locked away in the U.S. and Russia, but at least twice in the last few years, samples of the disease have been found in old storage closets. And as the permafrost covering our northern environs melts, there’s concern that ancient viruses, including smallpox, could again be unleashed. Terrorists dream of biological warfare, and a 2001 military simulation showed how unprepared the United States is for an outbreak. It turns out that the old gods are only sleeping, ready to awake at any moment.

Adam Rodman is a hospitalist and the host of the podcast Bedside Rounds, which can be found on iTunes and Stitcher. He can be reached on Twitter @AdamRodmanMD.

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