Title page of Zabdiel Boylston's An Historical Account of the Small-pox Inoculated in New England.
Photo: Wikimedia Commons

Looking for a new vaccine for smallpox, a virus that has been considered eradicated for decades, a team of scientists used genetic engineering to create a version of an analogue found in horses.

The work will lead to a safer live vaccine for smallpox, write the scientists from the University of Alberta and a pharmaceutical company in New York in PLoS ONE.

But critics have wondered whether the work is necessary at all – and whether it may actually provide a blueprint for future biological warfare or terrorism, according to reports.

The groundbreaking nature of the work is apparently agreed upon by all, both the scientists and the critics alike.

“We believe this is the first complete synthesis of a poxvirus using synthetic biology approaches,” they write.

The scientists, from the Canadian school as well as pharma company Tonix, started their joint viral work with a look into the breakthrough by Edward Jenner, a British doctor, who invented the first smallpox vaccine in 1796.

They produced the virus by creating a patchwork strand of DNA. Starting with 10 large fragments of DNA based on the horsepox virus, they were then included with two modern vaccinia virus end sequences. Those creations were then recombined with a live synthetic sequence of horsepox in Shope fibroma virus-infected cells, they write.

The creation of this pox virus could provide the template for many other such creations, according to the scientists.

“Most viruses could be assembled nowadays using reverse genetics, and these methods have been combined with gene synthesis technologies to assemble poliovirus and other extinct pathogens like the 1918 influenza strain,” they write. “Given that the sequence of variola virus has been known since 1993, our studies show that it is clearly accessible to current synthetic biology technology, with important implications for public health and biosecurity.”

Science first covered the developing study, and the consequent biological security concerns, last July. The magazine last week quoted several biosecurity experts warning that the work was a “serious mistake” and could provide a blueprint for ill-intentioned science.

Smallpox plagued humanity for centuries, claiming millions of lives, before vaccination eradicated it in 1980. Currently, first responders are inoculated against the virus due to biological warfare and terrorism fears. But even though the last known samples are held in labs in Russia and the United States, there are other traces left. Besides the genetic sequence of variola virus, which has been widely known since 1993, samples of the smallpox DNA are available in remains from centuries ago, as demonstrated in the journal Current Biology about a year ago.

Virologist David Evans (right) and researcher associate Ryan Noyce synthesized a horsepox virus using a published genome sequence. The synthetic virus could potentially be used to create a new vaccine against smallpox in humans. Photo: Melissa Fabrizio