Canadian researchers revived an extinct horsepox virus last year on a shoestring budget, by using mail-order DNA. That may not seem like a big deal, until you consider that this relatively inexpensive technique could be used by anyone — perhaps even to bring back something like smallpox, one of the most feared diseases in humanity’s history. The team’s research — which remains unpublished — was intended to create better vaccines and even cancer treatments. Though David Evans of the University of Alberta, the research lead, admitted that he also undertook the project to prove that it could be done. And, that it wouldn’t necessarily require a lot of time, money, and even biomedical skill or knowledge. As he told Science, “The world just needs to accept the fact that you can do this and now we have to figure out what is the best strategy for dealing with that.” Thus reigniting a powerful debate in the biomedical science community.
The researchers bought overlapping DNA fragments from a commercial synthetic DNA company. Each fragment was about 30,000 base pairs long, and because they overlapped, the team was able to “stitch” them together to complete the genome of the 212,000-base-pair horsepox virus. When they introduced the genome into cells that were already infected with a different kind of poxvirus, the cells began to produce virus particles of the infectious horsepox variety. While horsepox doesn’t infect humans, other pox viruses do: and if the technique works to recreate one kind of pox virus, it could likely work for others as well. This technique was first demonstrated by another group of researchers in a Proceedings of the National Academy of Sciences paper in 2002.
The idea that it would someday be possible to synthesize poxviruses is nothing new. In 2002, virologists assembled the poliovirus from scratch. However, this new work certainly does raise disturbing questions about how modern biotechnology could help terrorists weaponize viruses, which has in turn prompted a discussion about the regulation of science: “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,” Northern Arizona University anthrax expert Paul Keim told Science.
This work also changes the longstanding debate about what to do with the world’s few remaining smallpox samples. While scientists have argued about whether to destroy them or study them, if the viruses — or viruses very much like them — could be manufactured, it wouldn’t matter what happened to those samples. “You think it’s all tucked away nicely in freezers, but it’s not,” National Institutes of Allergy and Infectious Diseases virologist Peter Jahrling told Science. “The genie is out of the lamp.”
This brings us back to David Evans of the University of Alberta, who led the horsepox research. Pox viruses are common and infect many animals (including humans), but after it was eradicated, what’s left of the dreaded smallpox virus is held at CDC and cannot be studied. Evans had initially requested the use of existing horsepox samples from the CDC, but his request was declined because his purposes were commercial. So, instead, he synthesized a new virus instead, hoping to gain some insight into creating better vaccines. “This is the most successful vaccine in human history,” Evans said of the smallpox vaccine in Science, “the foundation of modern immunology and microbiology, and yet we don’t know where it came from. There is a huge, interesting academic question here.”