Laboratories around the world are racing to understand COVID-19, the potentially lethal virus that has upended everything from our personal lifestyles to the underpinnings of the global economy. Such work is also taking place in David Evans’ lab at the University of Alberta, where he contrasts the public perception of it with research he conducted just a few years ago on another threatening virus.
In 2017, Evans’ group in the university’s Department of Medical Microbiology & Immunology completed an ambitious reconstruction of a horsepox virus. This relative of smallpox, which does not affect humans, was formally considered to be extinct, but their work reproduced it in its entirety using the genome sequence as a guide. For Evans, it was a key demonstration of the powerful molecular tools that can be wielded for synthetic biology, but for many others it was regarded as an ethically fraught exercise.
“Eradicating smallpox, one of the deadliest diseases in history, took humanity decades and cost billions of dollars,” stated a critical article in Science. “Bringing the scourge back would probably take a small scientific team with little specialized knowledge half a year and cost about $100,000.”
That charge insisted that this work, which was published in the open access journal PLoS, served as nothing less than a blueprint for potential terrorists to likewise reconstruct their own version of deadly smallpox — along with other candidate organisms — for use in biological warfare. Evans formally responded in a follow-up article describing the demanding intricacy of working with viral components, which would pose a serious challenge to anyone seeking to “weaponize” them.
Evans acknowledged that the growing scope of synthetic biology techniques has made it impossible to consider any disease-causing organism to be regarded as “gone”, since they could be revived in one form or another. However, he argued that the benefits introduced by these techniques far outweigh any threat, since they dramatically increase the speed of working with complex viral components while also reducing the associated cost. He adds that those benefits are all too clear now, in light of the urgent call for a vaccine or some kind of targeted treatment to deal with the current health crisis.
“If you look across the spectrum of all the work that’s going on with COVID-19 right now, I would hazard a guess that every single bit of it is dependent on synthesizing the bits of the COVID virus genome that people want to study,” says Evans.
Evans’ lab has extensive knowledge of vaccinia virus, which is the virus that was used to vaccinate against mallpox. So he and his colleagues have synthesized some of the genes from SARS-CoV-2, the virus responsible for COVID-19, and inserted them into vaccinia virus in order to express different proteins. One of those recombinant vaccinia viruses could then serve as a prospective vaccine, which could be injected into the human body to generate an immune response to SARS-CoV-2 without being infected by the virus.
That might sound like a straightforward, if labour-intensive exercise, but Evans emphasizes just how difficult it can be. In order to synthesize and clone SARS-CoV-2 genes, they must first be assembled from smaller DNA fragments into larger fragments and then the larger fragments propagated in a benign source, such as yeast or E. coli. Yet just as the virus itself may be toxic, sometimes these DNA clones are also toxic and that make can make it impossible to prepare the genetic material.
“Those kinds of technical hurdles take a lot of scientific ingenuity to overcome,” observes Evans. “People who haven’t grown a virus in their lives say ‘well, we’re going to have a vaccine in a few weeks’.”
In fact, he adds, the long and winding path to this result represents the very obstacle that would make the process far too daunting even for the most dedicated of terrorists. Above all, it is also why he dismisses conspiracy theories about COVID-19 having been created in a laboratory for nefarious purposes.
“To do that, you would need to know all of the virus proteins and how they fit together,” he concludes. “Which means you must also know all of the structures of all of those proteins and how the structures interact. But we don’t have a technology yet perfected for taking a genome sequence and accurately predicting the structures of all of the encoded proteins. It’s highly unlikely that anyone would have made this virus de novo, just because there is no virologist who would claim to understand well enough just how all the bits go together to make a virus. If you knew enough about a virus to make it from scratch, you would also know enough about it to cure it.”