Designer pathogensAssessing the risks, benefits of horsepox synthesis

Published 19 March 2018

Truly assessing the risks and benefits of the recent horsepox synthesis is not an easy task. Two of the latest articles analyzing the implications of this research have been released in mSphere. They point to the increased attention on DURC [dual use research of concern] and the debate surrounding the benefits of a new vaccine versus the potential for a nefarious actor to misuse the process.

Nine-headed Hydra or cleaning out the Augean stables? Saskia Popescu  writes in Pandora Report that none of these tasks were particularly easy, and neither is truly assessing the risks and benefits of the recent horsepox synthesis.

Two of the latest articles analyzing the implications of this research have been released in mSphere. In the editorial, Michael J. Imperiale points to the increased attention on DURC [dual use research of concern] and the debate surrounding the benefits of a new vaccine versus the potential for a nefarious actor to misuse the process.

“The two articles posted today come from Gregory Koblentz at George Mason University, who argues that this work was poorly justified on two fronts, scientifically and commercially, and from Diane DiEuliis and Gigi Gronvall from National Defense University and the Center for Health Security at Johns Hopkins University Bloomberg School of Public Health, respectively, who discuss this study in the larger context of how the risks and benefits of dual use research are assessed and managed. (mSphere asked the leadership of Tonix to submit a manuscript, but we received no response.)”

Koblentz first underlines the weak scientific foundation for the claim that the horespox synthesis aids in the development of a new smallpox MCM. He states that the “combination of questionable benefits and known risks of this dual use research raises serious questions about the wisdom of undertaking research that could be used to recreate variola virus.”

Within his commentary, Koblentz addresses the scientific and commercial rationale for synthesizing the virus as well as the weak scientific basis for its use as a safer alternative for human vaccine use and the lack of demand for a new smallpox vaccine. “At the heart of the dual use research dilemma is the need to assess and balance the benefits and risks presented by an experiment or line of research. This is a difficult task given the largely theoretical risks posed by unknown adversaries in the future and the enticing yet uncertain benefits that the research may eventually yield. Indeed, measuring risks and benefits and weighing them can be a wicked problem that defies simple or straightforward conclusions. The difficulty of the task, however, does not excuse researchers, funders, or journal editors from trying to do so. While the benefits of biotechnology and life sciences research are beyond question, we should not take for granted the benefits of specific experiments or avenues of dual use research.”

In their counterpoint article, Diane DiEuliis and Gigi Kwik Gronvall emphasize that the horsepox researchers went through due biosecurity diligence at their research institution, the importance of utilizing an analytical framework for assessing the risks and benefits of DURC, and discuss “relevant components of biosecurity policy and the biodefense enterprise (including the acquisition of medical countermeasures) in the United States.”

DiEuliis and Kwik Gronvall point to the horespox synthesis (and the controversy) as an opportunity to evaluate how dual-use risks should be handled, the complicated approach to stockpiling MCM, and “the challenges of forecasting risks and benefits from a particular scientific discovery or technology”. They highlight the National Academies Imperiale report framework for evaluating the capacity for technology to be misused, which includes factors like weighing the use of the technology itself against consequence management, etc.

They also note three issues that have been raised by the horespox paper that require additional consideration – “The decision of what to do with a technology or research area that is dual use cannot be black or white, MCMs cannot be a check-the-box procedure for the USG, The synthesis of and booting up of a pathogen should serve as strategic warning that current biosecurity controls and preparedness are insufficient.”

DiEuliis and Kwik Gronvall note that “Now that the work has been published, the authors examined the research according to the Imperiale report framework, which aims to provide a systematic way to evaluate biosecurity risks. We again found that while dual use information would benefit highly experienced actors who are intent on misuse, the recreation of smallpox virus may require additional research and development steps than have been described in this publication: smallpox virus is less similar to horsepox virus than horsepox virus is to vaccinia virus, the tools to recreate horsepox virus were originally developed for vaccinia virus, and they might require additional troubleshooting for re-creation of smallpox virus.”