In July 2014, long forgotten vials of smallpox left in a cardboard box were discovered at a research centre near Washington. Until then, it was believed that only two places on Earth guard the last remaining samples of this killer virus. As Rachel Nuwer discovered in this feature, first published in January 2014, they may not be there for long.

For the first 12 days, you go about your life normally, unaware that these may very well be your last.

Then at around day 13, the virus erupts out of infected cells and pours into your blood stream. Fever, headache, vomiting and intense body aches leave you too sick to function. At this point, however, there’s still hope: perhaps you’ve just contracted the flu.

Around day 17, however, those prayers are dashed. The first telltale spots begin to break out on your tongue and inside your mouth. These quickly spread across your body, concentrating in the extremities. The pea-sized bumps soon fill with a thick liquid – the detritus of your ravaged tissues – and develop a donut-like indentation. For those who dare touch them, they feel like small pebbles embedded under the skin. If you survive – and 30% of people do not – the papules will form a crust, eventually falling off as scabs and leaving you with life-long pitted scars.

That’s what happens when you are infected by Variola major virus – better known as smallpox. An estimated 300 million people died from smallpox in the 20th Century alone, making it one of history’s biggest ever viral killers.

Thankfully, however, smallpox was stamped out more than three decades ago, and now there are only a few samples of smallpox left on Earth. Where are they? Why are they there? And could 2014 be the year that we finally destroy the last of this killer virus once and for all?

In 1975, the last naturally occurring case of Variola major turned up in a two-year old girl in Bangladesh. Finally, after three decades of eradication efforts, on 8 May  1980, the World Health Organization pronounced success, writing: “The world and its peoples have won freedom from smallpox, which was a most devastating disease sweeping in epidemic form through many countries since earliest time, leaving death, blindness and disfigurement in its wake.”

This was possible because unlike most deadly viruses – such as Ebola, yellow fever, HIV, or influenza – smallpox has no animal reservoir. Without human incubators, the virus cannot naturally exist.

It also doesn’t stay alive on its own for long. In the past, some researchers and news outlets speculated that smallpox in the frozen graves of former victims might remain in suspended animation, ready to begin a new cycle of infection should those bodies ever be dug up and thawed. Scientists have attempted to excavate corpses in frozen graves in Alaska and Siberia that contain the remains of smallpox victims, however none of the bodies contained viable viruses. “No one feels there’s a serious chance that global warming will melt the permafrost and unleash an epidemic,” says Michael Lane, who served as director of the Centers for Disease Control’s (CDC) smallpox eradication programme from 1970 until 1981, when it was declared a success and shut down.

Chilling case

After smallpox was eradicated from the environment, a handful of labs across the world kept live samples of the disease for research purposes, such as developing treatments and vaccines. In 1978, however, the dangers became clear. Janet Parker, a photographer working at the University of Birmingham Medical School, began complaining about headache and muscle pains. Days later, red spots appeared on her body, which medical workers wrote off as a harmless rash. Two weeks after her symptoms began, however, doctors correctly diagnosed smallpox. She was quarantined and treated for her illness, but died around two weeks later. Her mother also fell ill but survived, while her father suffered a fatal heart attack during a visit to see his daughter in the hospital.

Parker had somehow been exposed to the virus, which had likely traveled through air ducts to her office from a lab downstairs where researchers kept samples of smallpox. Henry Bedson, the head of the university’s medical microbiology department, blamed himself for Parker’s death and cut his throat several days before Parker passed away.

This distressing series of events triggered a complete rethink about keeping stores of the smallpox virus for research. “Although we all had in the back of our minds that we needed to extirpate the virus – not just the disease – that incident made us realise that the repository of smallpox in test tubes and screw-top vials in various labs was a major problem,” Lane says.

The World Health Organization quietly put out a call for all samples of the virus to be either destroyed or sent to one of two official repositories: a CDC lab near Atlanta and the Vector Institute in Koltsovo, Siberia. A handful of samples quickly came in, arriving from India, Japan, the UK and other locations. “It very quickly became obvious that nobody wanted the virus in their lab anyway,” Lane says. “They were delighted to give this stuff up.”

Viral tomb

Currently, smallpox is known to be kept only at those two locations. (While previously unknown vials were discovered in a Washington lab in July 2014, they were soon transported to Atlanta.) Both house the virus in biosafety level four (BSL-4) facilities. This level of safety – the highest possible – requires researchers to wear a positive pressure suit that resembles those worn in space and includes a tethered air supply. All manipulation with the virus, which is stored in liquid nitrogen tanks, is done in bio-safety cabinets. When exiting the lab, researchers spend seven minutes in a chemical shower to disinfect themselves, followed by a water rinse. No air escapes from within the BSL-4’s rooms, and each year the CDC lab is shut down for a month to undergo preventative maintenance.

While the CDC is located on the fringes of bustling Atlanta, the Russian smallpox repository, Vector, has an additional safety measure – it is in the middle of nowhere.

Security at both locations is formidable. “I was director of smallpox programmes for many years, and I live one mile from the CDC,” Lane says. “I can’t even get into the building – not just the lab – where smallpox virus is kept.”

Only a small number of researchers are permitted to enter these chambers. For some, it’s just another day on the job. “I cut my teeth working on BSL-4 viruses,” says Peter Jahrling, director of the National Institute of Allergy and Infectious Disease’s Integrated Research Facility, and chief of the Emerging Viral Pathogens Section. “I work with Ebola, Lassa and Marburg, so smallpox is a walk in the park.”

Others, however, maintain a sense of reverence for the disease. “This is a virus that wreaked terrible havoc on the human population, and efforts to control and eradicate that disease were heroic,” says Inger Damon, chief of the poxvirus and rabies branch at the CDC’s Division of High-Consequence Pathogens and Pathology. “I don’t think you ever become immune to that sense of awe.” 

Nowhere else?

So how do we know that additional smallpox samples are not also hoarded away in some terrorist hideout, or stuck in an old vial in the back of a forgotten freezer? “We don’t,” Lane says. “There’s no way to prove a negative.”

Still, things look good for the disease’s confinement to the CDC and Vector. Since the late 1970s, as far as experts know, no one has contracted smallpox. At the same time, no terrorists have come forward claiming they have the virus and no rumours have circulated of it being kept in some secret lab.

Except, that is, for one suspicious case. In 1992, Ken Alibek – formerly Colonel Kanatzhan Alibekov – defected from Russia to the US. Alibek served as the first deputy director of Biopreparat, the Soviet Union’s biological warfare agency, founded in 1973. After arriving in the US, Alibek began making allegations against his former nation, claiming that the Soviet Union had produced 50 tons of smallpox. Biopreparat, he claimed, had employed a scientific army of 30,000 people who worked on smallpox and other pathogenic weapons, such as Ebola, anthrax and plague.

Could this be true? “It’s no secret that smallpox virus was developed as a biological weapon and produced on an industrial scale,” Jahrling says. “Is it possible that someone kept a little retirement package in his freezer? It’s not impossible.”

But some – including Lane – doubt Alibek’s claims, and point out there’s no evidence. “The fact that nobody knows for sure whether this happened is the major factor that makes people nervous, even though there’s no solid reason to believe it,” says Lane.

Last to go

Now the last remaining virus samples in Atlanta and Russia might finally be headed for eradication.

This summer, the World Health Assembly – which acts as a sort of congress for the WHO – will vote about whether or not to destroy the remaining smallpox samples. The Russian delegation has consistently voted against this path, so there is a chance that Russia would not comply if the vote turned in favour of destroying the virus. For the US, however, “it would be extremely embarrassing for us not to go along with the official WHO recommendation,” Lane says. “We’d basically be thumbing our nose at the UN.”

The Russians are not alone in wanting to keep smallpox. Some scientists say that more research needs to be done on the complex genetics of the virus, which could help devise more effective antivirals, for example. “I know many in this country feel there’s important research to be done, and that it really doesn’t make a lot of sense to acquiesce to some symbolic act,” Jahrling says.

Damon also sees the logic in keeping smallpox around. “I’ve changed my mind many times, and when I first came to this position at CDC, I didn’t really see a need to use the live virus,” she says. “But I think if we’re going to develop a better understanding of the virus, having access to it is critical.” 

Dissenters, on the other hand, claim that most of that work can be done with the much less virulent Vaccinia virus or other related viruses. “It almost becomes a theological argument: either you believe you need it or you don’t,” Jahrling says.

Wouldn’t destroying it make certain once and for all that it’d never fall into the wrong hands though? The truth is, even it were destroyed, existing lab techniques could in principle recreate it based on the smallpox genome, which has been sequenced.

That begs the question: why hasn’t anyone done that already? If a terrorist group, say, did have the means of creating smallpox, the effort may not be worth it compared with other methods of terrorism, such as the use of chemical weapons, says Lane. Vaccines exist to contain smallpox’s spread, and it isn’t the most contagious of pathogens. A smallpox outbreak would no doubt be a catastrophe, but there are worse things that could be unleashed on a population. We beat smallpox once and we could beat it again.

For now, at least, smallpox lives on – somewhere deep inside two very special labs; the only two places left on Earth where one of history’s biggest killers still thrives.

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