The publication of the experimental work that synthesized horsepox is imminent, according to multiple reports. Horsepox no longer exists in nature, so this was the creation of an extinct virus in the same genus as smallpox. It doesn’t infect people, but causes pox disease in horses. Researchers have cited several objectives for the work, including the intention to develop it as a smallpox vaccine, the intention to develop it as a virus-based cancer treatment, and the intention to show that synthesizing smallpox de novo is possible.
The work raises a number of serious questions and concerns, partly about the specifics of the work and partly about what this says about biosecurity and biosafety considerations related to a circumscribed set of experiments.
The first question is whether experimental work should be performed for the purpose of demonstrating something potentially dangerous and destructive could be made using biology. In this case, horsepox was created in the laboratory, at least in part to show that synthesis de novo of smallpox virus is feasible. In this specific case, leading virologists have agreed for many years that de novo smallpox synthesis was scientifically feasible, and there has been no serious counterargument that it was not feasible. But the important decision going forward is whether research with high biosafety or biosecurity risks should be pursued with a justification of demonstrating that something dangerous is now possible. I don’t think it should. Creating new risks to show that these risks are real is the wrong path. At the very least, it’s a serious issue needing serious discussion.
A second question that is more relevant to this experiment is how much new detail will be provided in the forthcoming publication regarding how to construct an orthopox virus. It is one thing to create the virus; it’s another thing altogether to publish prescriptive information that would substantially lower the bar for creating smallpox by others. The University of Alberta lab where the horsepox construction took place is one of the leading orthopox laboratories in the world. They were technically able to navigate challenges and inherent safety risks during synthesis. Will labs that were not previously capable of this technical challenge find it easier to make smallpox after the experiment methodology is published?
A third question relates to the approval process for experimental work with implications for international biosecurity or international biosafety. The researchers who did this work are reported to have gone through all appropriate national regulatory authorities. Researchers who created horsepox have said that the regulatory authorities “may not have fully appreciated the significance of, or potential need for, regulation or approval of” this work. So while work like this has potential international implications – it would be a bad development for all global citizens if smallpox synthesis becomes easier because of what is learned in this publication – the work is reviewed by national regulatory authorities without international norms or guidelines that direct them. This means that work considered very high risk and therefore rejected by one country may be approved by others.
In the case of the horsepox experiment in Canada, the Advisory Committee on Variola Virus Research at WHO was briefed on the work after it was completed. Moreover, the primary charge of that committee is actual smallpox research itself (as opposed to horsepox). Beyond that, this WHO committee is unique. WHO does not have special disease by disease committees that review work on a case by case basis for other pathogens.
I think the new P3CO policy published by the White House in January 2017 could be a good step forward in the US regarding future policy development for experiments involving potential pandemic pathogens. Whether and how that policy will be implemented remains to be seen since it is guidance for federal agencies but does not require their action. Importantly in this case, even if this policy had been implemented in the US, it doesn’t seem that the policy would have had bearing on the horsepox research had that been proposed in the US. So even as the US has spent a substantial amount of time considering these kinds of issues, it still doesn’t have policy (or high-level review committees) that directly considers experiments like this. Beyond that, there is no international component to P3CO. There clearly needs to be an international component to these policies. We need agreed upon norms that will help guide countries and their scientists regarding work that falls into this category, and high-level dialogue regarding the necessary role of scientific review, guidance, and regulation for work that falls into special categories of highest concern. It is not clear that these considerations are now even being discussed internationally.
The rapid advance of biology in the world overall will continue to have enormous health and economic benefits for society. The entrepreneurial and unpredictable nature of biological research, now coupled with powerful global markets, is overwhelmingly positive for the world. But this case of horsepox synthesis shows us that there are also specific and serious challenges that require special attention now.
Tom Inglesby, MD, is the director of the Johns Hopkins Center for Health Security