The problem of horsepox synthesis: new approaches needed for oversight and publication review for research posing population-level risks

By Tom Inglesby

In summer 2017, a team of Canadian scientists revealed that they had synthesized the horsepox virus in a lab at the University of Alberta, and planned to publish their research. I and others expressed strong concern about the work at that time, and we have opposed its publication. 

Today, the science journal PLOS ONE published this research online, so it is now globally available. The horsepox researchers acknowledged that this work may lower the bar for other scientists interested in synthesizing smallpox. Before its eradication from nature in 1980, smallpox was humanity’s greatest infectious disease killer. Almost none of the global population in 2018 has effective immunity, and smallpox vaccine supplies are available only to protect a small fraction of the world. There are only two declared smallpox repositories, one in the United States and one in Russia. Any research that reduces the challenges of synthesizing smallpox de novo outside these repositories—as this work does—should be off limits unless, perhaps, there were to be extraordinary benefits that make the risks worth taking.

This work does not carry such extraordinary benefits. As Greg Koblenz has articulated in his paper on this issue, there is not a compelling case that governments will need or use this virus to develop a new and improved smallpox vaccine. Another justification made by the horsepox researchers was that it is important to demonstrate the feasibility of synthesizing smallpox de novo. But creating a new extraordinary risk (i.e., instructions for how to simplify smallpox synthesis) to show that the risk is legitimate is a dangerous path. In any event, relevant members of the science community have widely agreed that smallpox synthesis has been technically feasible for many years now. What this new research does is show the global scientific community how to synthesize orthopox viruses in an efficient way, to overcome technical challenges, and to employ techniques developed by one of the leading orthopox labs in the world.

Now, with this research published and accessible to the world, those of us who are deeply concerned about it should consider what is needed to prevent future events with such potential harmful impact. This horsepox synthesis research work has exposed serious flaws in how governments oversee research that has profound potential population-level adverse consequences. The University of Alberta research team admitted that regulatory authorities “may not have fully appreciated the significance of, or potential need for, regulation or approval of” their work. Clearly, fundamental changes need to be made. 

The most important locus of control should be whether specific research is approved and funded in the first place. When scientists are considering the pursuit of research that has the potential to increase highly consequential national population-level risks, national authorities and leading technical experts on those issues should be part of the approval process. When there are highly consequential international population-level implications, international public health leaders should also be involved. When researchers put forth claims about potential benefits of this work to justify extraordinary risks, those claims ought not be accepted without discussion; those claims should instead be examined by disinterested experts with the expertise to validate or refute them.

If research posing potential population-level risks does get performed without such high level national or international scrutiny, or without a disinterested examination of the benefits, publishers should have clear guidance from governments and a process for engaging with governments in the decision-making process regarding publication. That kind of system is not in place in the United States or elsewhere. Journals are now often on their own, in some cases with the help of a dual-use research committee that is comprised of individual scientists who may or may not have full understanding of the potential risks or the claims of benefits of the underlying research being published.   

We need to turn what we’ve learned from this damaging situation into actionable policies aimed at strengthening preparedness and global health security. The first step is changing the oversight and approval process for experiments that have potential to create highly consequential population-level risks. We also need a coinciding publication review system for such research with the scientific and government input necessary to avoid publishing research that increases risks to global populations.