Medical Examiner

The Persistent Danger of Poxes

Where else could smallpox be found?

Skin cells infected with smallpox.
Skin cells infected with smallpox, once a fearsome killer.

Courtesy of the CDC

Like a plot twist in a bad Syfy network movie, the Centers for Disease Control and Prevention announced on Tuesday that vials labeled “variola”—aka smallpox—were discovered in an unused storage room in a Food and Drug Administration laboratory. The vials, dating to the 1950s, were immediately placed in a high-security lab in Maryland before being shipped to the CDC, where the presence of smallpox was confirmed.

Smallpox used to be a fearsome killer. Fatality rates were approximately 30 percent, though they could be higher in some populations, especially those with no previous exposure. When Europeans carried the disease to the New World, it devastated Native American populations, killing 50 percent or more in a given outbreak. During the 20th century alone, somewhere between 300 million and 500 million people are estimated to have died from the virus.

Following a lengthy worldwide vaccination campaign, smallpox was officially declared eradicated in nature in 1980, after the last human case in the wild was seen in 1977. Stocks of the smallpox virus were subsequently destroyed, and, before Tuesday, the only known remaining vials were held in two laboratories: one in Russia and the other in the United States at the CDC.

Laboratory vials aside, is there any way smallpox could escape into the human population? Could some other similar virus take its place? How worried should we still be about what was one of the deadliest diseases in the history of the world?

The very method of smallpox immunization may have left remnants of the virus behind. Before vaccination with a related virus, vaccinia, was introduced by Edward Jenner in 1798, people would take scabs from a smallpox patient and scratch bits of those scabs into the skin of a person who’d never been infected with smallpox.* This often caused a mild infection, but it offered lifelong protection from the deadly disease. These scabs were sometimes stored in houses or even mailed to relatives, and they could work even after long periods of storage. One experiment tested smallpox crusts yearly for 13 years to determine if they were still infectious. The experiment ended not because the scabs had lost the ability to infect—they hadn’t—but because the scientists had simply used up all the scab material available.

Beyond stored scabby remnants, smallpox may still exist in suspended animation within buried corpses or mummified human remains. Particularly when a body has been well-preserved after succumbing to smallpox, there is a small chance that live virus may be present. This was a concern with the examination of Ramses V, the Egyptian pharaoh who appeared to have smallpox lesions; with corpses found in the Siberian permafrost ; and with bodies unearthed during construction projects in the United States. Though the live virus hasn’t been isolated from any cadavers to date, that’s not to say it can’t be out there … somewhere. After all, researchers were able to obtain influenza RNA (but not a live virus) from a corpse that had been buried in frozen Alaskan ground for almost 75 years, a victim infected during the 1918 influenza pandemic. Permafrost in particular appears to be great at harboring viruses in a cryogenic state: A 30,000-year-old virus was recently resurrected from the permafrost’s cold depths and coaxed to replicate.

Even if smallpox remains contained within labs in the U.S. and Russia (or exterminated completely, as has been discussed many times since the virus’ eradication in nature), other related viruses may prove to be similarly deadly. For the first time in centuries, we have a population in which immunity to smallpox is becoming a rarity, as older generations who were exposed naturally or immunized via vaccination are dying off. In the United States, smallpox vaccines haven’t been given to the general public since 1972, meaning that half of Generation X and all of the millennials are susceptible to the virus.

And that makes them more susceptible to related viruses as well. Smallpox is but one of a family of viruses called orthopoxviruses. Another member of the family, vaccinia, so closely related that it’s used in the smallpox vaccine, causes a relatively mild infection in humans.

Perhaps the most concerning orthopoxvirus is monkeypox, a virus originating in African rodents that causes symptoms similar to smallpox in humans. It’s called monkeypox because monkeys show smallpox-like symptoms, but the rodents are where the virus usually lives. Fatality rates in humans can be as high as 8 percent. In the Democratic Republic of Congo, scientists have seen a twentyfold increase in monkeypox infections over the past 30 years—that is, in the time since smallpox vaccination has ceased in that area. For now this infection does not spread efficiently among humans. It is instead a zoonotic disease—one that is spread to humans from animals. However, some evidence suggests that as vaccine protection is decreasing, the potential for human-to-human transmission of monkeypox is on the rise.

Furthermore, monkeypox can jump continents via its animal reservoir hosts. A large monkeypox outbreak occurred in the Midwest in 2003, when cages of Gambian rats were housed alongside prairie dogs for sale at pet stores in several states. A total of 71 people were infected over the course of a month, though no deaths were reported.

Camelpox is another smallpox cousin that may infect humans, though such infections seem to be rare. And there are certainly other orthopoxviruses that have yet to be discovered. One such virus was found recently in the country of Georgia, where two herdsmen became sick with what appeared to be anthrax, a bacterial disease that can infect livestock. However, tests showed that it instead was an orthopoxvirus that had never previously been reported.

It’s been estimated that there are approximately 320,000 undiscovered mammalian viruses ensconced in host species, hiding in plain sight, unidentified until they sicken or kill livestock or people. More orthopoxviruses are sure to be among these.

Having additional information about the diversity of orthopoxviruses that exists in other species would help shed light on where smallpox came from in the first place. A rodent origin is likely—thousands of years ago, a rodent orthopoxvirus jumped into the human species, perhaps over and over again as the virus mutated and accumulated genetic changes that eventually allowed it to spread among humans, independent from its previous rodent ancestor. Might this happen again with monkeypox or an undiscovered orthopoxvirus? Possibly.

If we do experience an orthopoxvirus outbreak from smallpox, monkeypox, or something else entirely, the U.S. does have a stockpile of smallpox vaccine—enough to immunize every citizen. Once the nature of the outbreak is identified, that is. Still, whether the exposure comes from an inadvertent contact with a hidden orthopoxvirus in nature or after stumbling upon great-grandpa’s stash of smallpox scabs in the attic, rest assured that a return to the days of hundreds of millions of smallpox deaths is unlikely.

Correction, July 11, 2014: Due to a production error, the caption for the photo in this article originally identified the cells infected with smallpox as smallpox.

Correction, July 14, 2014: This article originally misstated Edward Jenner’s first name as Edwin. (Return.)