Synthetic viruses—Anything new?

Synthetic horsepox virus raises concernsThe report of the construction of an infectious horsepox virus from synthesized DNA by Noyce, Lederman, and Evans [1] raised considerable concerns about whether this study will facilitate the construction of smallpox virus (variola) using synthetic biology [2][3][4][5].This is a valid concern, but for a number of reasons-as explained below-no major change concerning the likelihood of a "resurrection" of smallpox emerges from this publication.Having said this, it is also evident that the scientific community, politicians, decision makers, and the lay public have to continue, and probably intensify, a discussion on benefits and risks of synthetic biology in a broader sense. What has been done?The study "Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments" was conducted in the laboratory of Dr. Evans, University of Alberta, Canada.The authors describe a workflow from chemically synthesized DNA to the rescue of infectious horsepox virus with the intention to generate a horsepox virus-based vaccine that may be equally as efficacious as vaccinia virus-based vaccines but may have less severe side effects.Since the introduction of vaccinia virus as a vaccine against smallpox by Edward Jenner more than 200 years ago, the origin and passage history of this vaccine have remained elusive.However, recent sequencing data revealed close similarities between horsepox and vaccinia viruses, suggesting that horsepox virus might serve as a candidate smallpox vaccine [6][7][8].There is just one problem: there have been no horsepox virus infections reported since the 1980s, and the virus might actually be extinct [9].Therefore, Evans and colleagues set out to "resurrect" horsepox virus from synthesized DNA.To achieve this, they made use of (i) the ability of poxviruses to facilitate homologous recombination, (ii) a helpervirus (Shope fibroma virus) to launch poxvirus replication from naked DNA [10], and (iii) recent advances in synthetic biology, namely, the ability to chemically synthesize large DNA fragments. Anything new?The authors are now blamed for providing a workflow that allows for the generation of any infectious poxvirus, including smallpox virus, from synthesized DNA (Fig 1).But is this actually new?According to the PLOS Dual Use Research of Concern (DURC) Committee, "The study did not provide new information specifically enabling the creation of a smallpox virus, but uses known methods, reagents and knowledge that have previously been used in the synthesis of other viruses (such as influenza and polio viruses)" [5].Indeed, the individual experimental steps and methods to generate infectious horsepox virus have been reported before.