Designer pathogensThe synthesis of horsepox virus and the failure of dual-use research oversight

By Gregory Koblentz

Published 24 January 2018

On 19 January 2018, the open access scientific journal PLOS One published an article that describes the de novo synthesis of horsepox virus, the first ever synthesis of a member of the orthopoxvirus family of viruses that includes the variola virus that causes smallpox. This research crosses a red line in the field of biosecurity. Given the high degree of homology between orthopoxviruses, the techniques described in this article are directly applicable to the recreation of variola virus. The synthesis of horsepox virus takes the world one step closer to the reemergence of smallpox as a threat to global health security. The reemergence of smallpox would be a global health disaster. Prior to its eradication, smallpox killed an estimated 300 million people, more people than all the wars of the twentieth century combined. Based on these considerations, the horsepox synthesis research is all risk and no reward. Given the known risks of this research for pioneering a technique that can be used to recreate variola virus and its questionable benefits, the publication of this article represents a failure of PLOS One to exercise its responsibility to carefully consider the biosecurity implications of the research it publishes.

On 19 January 2018, the open access scientific journal PLOS One published an article that describes the de novo synthesis of horsepox virus, the first ever synthesis of a member of the orthopoxvirus family of viruses that includes the variola virus that causes smallpox. As I have written about before, this research crosses a red line in the field of biosecurity. Given the high degree of homology between orthopoxviruses, the techniques described in this article are directly applicable to the recreation of variola virus. The synthesis of horsepox virus takes the world one step closer to the reemergence of smallpox as a threat to global health security. That threat has been held at bay for the past forty years by the extreme difficulty of obtaining variola virus which has been eradicated from nature and is only known to exist in two WHO-designated repositories.

The reemergence of smallpox would be a global health disaster. Prior to its eradication, smallpox killed an estimated 300 million people, more people than all the wars of the twentieth century combined. Most of the world’s population is susceptible to this lethal and contagious disease since routine immunization against smallpox was discontinued after the success of the WHO’s global eradication campaign.

Per its policy on dual-use research, PLOS convened its Dual-Use Research Committee, composed of PLOS editors and outside experts, to review the manuscript. According to a statement from PLOS,

“The Committee was asked to consider the potential risks of this research, notably the risk that the study might provide new information which could be misused to construct a smallpox virus. They concluded that 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). In consideration of the benefits of publication of the research, especially the potential for improvements in vaccine development, the Committee unanimously agreed that in this instance, the benefits of publication outweigh the risks. The Committee therefore supported publication of this manuscript.”