How Canadian researchers reconstituted an extinct poxvirus for $100,000 using mail-order DNA
Eradicating smallpox, one of the deadliest diseases in history, took humanity decades and cost billions of dollars. Bringing the scourge back would probably take a small scientific team with little specialized knowledge half a year and cost about $100,000.
That's one conclusion from an unusual and as-yet unpublished experiment performed last year by Canadian researchers. A group led by virologist David Evans of the University of Alberta in Edmonton, Canada, says it has synthesized the horsepox virus, a relative of smallpox, from genetic pieces ordered in the mail. Horsepox is not known to harm humans—and like smallpox, researchers believe it no longer exists in nature; nor is it seen as a major agricultural threat. But the technique Evans used could be used to recreate smallpox, a horrific disease that was declared eradicated in 1980. "No question. If it's possible with horsepox, it's possible with smallpox," says virologist Gerd Sutter of Ludwig Maximilians University in Munich, Germany.
Evans hopes the research—most of which was done by research associate Ryan Noyce—will help unravel the origins of a centuries-old smallpox vaccine and lead to new, better vaccines or even cancer therapeutics. Scientifically, the achievement isn't a big surprise. Researchers had assumed it would one day be possible to synthesize poxviruses since virologists assembled the much smaller poliovirus from scratch in 2002. But the new work—like the poliovirus reconstitutions before it—is raising troubling questions about how terrorists or rogue states could use modern biotechnology. Given that backdrop, the study marks "an important milestone, a proof of concept of what can be done with viral synthesis," says bioethicist Nicholas Evans—who's not related to David Evans—of the University of Massachusetts in Lowell.
The study seems bound to reignite a long-running debate about how such science should be regulated, says Paul Keim, who has spent most of his career studying another potential bioweapon, anthrax, at Northern Arizona University in Flagstaff. "Bringing back an extinct virus that is related to smallpox, that's a pretty inflammatory situation," Keim says. "There is always an experiment or event that triggers closer scrutiny, and this sounds like it should be one of those events where the authorities start thinking about what should be regulated."
Little-noticed discussion
David Evans acknowledges that the research falls in the category of dual-use research, which could be used for good or bad. "Have I increased the risk by showing how to do this? I don't know," he says. "Maybe yes. But the reality is that the risk was always there."
Evans discussed the unpublished work in November 2016 at a meeting of the Advisory Committee on Variola Virus Research at the World Health Organization (WHO) in Geneva, Switzerland. (Variola is the official name of the virus that causes smallpox.) A report from that meeting, posted on WHO's website in May, noted that Evans's effort "did not require exceptional biochemical knowledge or skills, significant funds or significant time." But it did not draw much attention from biosecurity experts or the press.
Also little noticed was a press release issued by Tonix, a pharmaceutical company headquartered in New York City with which Evans has collaborated, which also mentioned the feat. Tonix says it hopes to develop the horsepox virus into a human smallpox vaccine that is safer than existing vaccines, which cause severe side effects in a small minority of people. Evans says it could also serve as a platform for the development of vaccines against other diseases, and he says poxvirus synthesis could also aid in the development of viruses that can kill tumors, his other area of research. "I think we need to be aware of the dual-use issues," Evans says. "But we should be taking advantage of the incredible power of this approach."
The double-stranded variola genome is 30 times bigger than the poliovirus genome, which Eckard Wimmer of State University of New York at Stony Brook assembled from mail-ordered fragments in 2002. Its ends are also linked by structures called terminal hairpins, which are a challenge to recreate. And though simply putting the poliovirus genome into a suitable cell will lead to the production of new virus particles, that trick does not work for poxviruses. That made building variola "far more challenging," says Geoffrey Smith of the University of Cambridge in the United Kingdom, who chairs WHO's variola advisory panel.
That's one conclusion from an unusual and as-yet unpublished experiment performed last year by Canadian researchers. A group led by virologist David Evans of the University of Alberta in Edmonton, Canada, says it has synthesized the horsepox virus, a relative of smallpox, from genetic pieces ordered in the mail. Horsepox is not known to harm humans—and like smallpox, researchers believe it no longer exists in nature; nor is it seen as a major agricultural threat. But the technique Evans used could be used to recreate smallpox, a horrific disease that was declared eradicated in 1980. "No question. If it's possible with horsepox, it's possible with smallpox," says virologist Gerd Sutter of Ludwig Maximilians University in Munich, Germany.
Evans hopes the research—most of which was done by research associate Ryan Noyce—will help unravel the origins of a centuries-old smallpox vaccine and lead to new, better vaccines or even cancer therapeutics. Scientifically, the achievement isn't a big surprise. Researchers had assumed it would one day be possible to synthesize poxviruses since virologists assembled the much smaller poliovirus from scratch in 2002. But the new work—like the poliovirus reconstitutions before it—is raising troubling questions about how terrorists or rogue states could use modern biotechnology. Given that backdrop, the study marks "an important milestone, a proof of concept of what can be done with viral synthesis," says bioethicist Nicholas Evans—who's not related to David Evans—of the University of Massachusetts in Lowell.
The study seems bound to reignite a long-running debate about how such science should be regulated, says Paul Keim, who has spent most of his career studying another potential bioweapon, anthrax, at Northern Arizona University in Flagstaff. "Bringing back an extinct virus that is related to smallpox, that's a pretty inflammatory situation," Keim says. "There is always an experiment or event that triggers closer scrutiny, and this sounds like it should be one of those events where the authorities start thinking about what should be regulated."
Little-noticed discussion
David Evans acknowledges that the research falls in the category of dual-use research, which could be used for good or bad. "Have I increased the risk by showing how to do this? I don't know," he says. "Maybe yes. But the reality is that the risk was always there."
Evans discussed the unpublished work in November 2016 at a meeting of the Advisory Committee on Variola Virus Research at the World Health Organization (WHO) in Geneva, Switzerland. (Variola is the official name of the virus that causes smallpox.) A report from that meeting, posted on WHO's website in May, noted that Evans's effort "did not require exceptional biochemical knowledge or skills, significant funds or significant time." But it did not draw much attention from biosecurity experts or the press.
Also little noticed was a press release issued by Tonix, a pharmaceutical company headquartered in New York City with which Evans has collaborated, which also mentioned the feat. Tonix says it hopes to develop the horsepox virus into a human smallpox vaccine that is safer than existing vaccines, which cause severe side effects in a small minority of people. Evans says it could also serve as a platform for the development of vaccines against other diseases, and he says poxvirus synthesis could also aid in the development of viruses that can kill tumors, his other area of research. "I think we need to be aware of the dual-use issues," Evans says. "But we should be taking advantage of the incredible power of this approach."
The double-stranded variola genome is 30 times bigger than the poliovirus genome, which Eckard Wimmer of State University of New York at Stony Brook assembled from mail-ordered fragments in 2002. Its ends are also linked by structures called terminal hairpins, which are a challenge to recreate. And though simply putting the poliovirus genome into a suitable cell will lead to the production of new virus particles, that trick does not work for poxviruses. That made building variola "far more challenging," says Geoffrey Smith of the University of Cambridge in the United Kingdom, who chairs WHO's variola advisory panel.
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