Synthesizing Biological Threats—A Small Leap From Horsepox to Smallpox

Earlier this summer, it was announced that a team of Canadian researchers led by virologist David Evans, PhD, had successfully synthesized the horsepox virus. This de novo synthesis was performed within the span of 6 months, utilizing mail-order DNA, $100,000, and “little specialized knowledge.” What is concerning about this experiment is that it highlights not only the possibility of synthesizing DNA with limited resources in a short window of time, but that it involved an orthopoxvirus, horsepox, a close relative of smallpox. This experiment has brought attention not just to the capacity and capabilities for people to do such experiments but also that there were little oversight and safeguards in place to ensure biosecurity and biosafety measures were followed. I will not go into the implications of publishing such methods.

Gregory Koblentz, PhD, MPP, director of George Mason University’s Biodefense graduate program, recently highlighted this experiment as a possible opening of Pandora’s box in terms of such risky research and what it means for the reemergence of smallpox. Dr. Koblentz pointed to the removal of barriers we traditionally cite as primary inhibitors of smallpox synthesis, such as the difficulty of obtaining variola virus and the availability of effective medical countermeasures. The horsepox synthesis experiment erased these barriers and moved toward establishing a concerning culture that normalizes the synthesis of orthopoxviruses, leaving room for biological errors (or terrors) should the proper safeguards not be put in place.

Pointing to gaps in the international legal framework and throughout the DNA synthesis industry, Dr. Koblentz suggests several strategies for preventing the return of smallpox, ranging from World Health Organization legislative recommendations to industry efforts that ensure annual training and compliance with codes of conduct.

Despite the devastating implications of this experiment, it received less media attention than experiments with the H5N1 influenza virus that has occurred years before. Recently, I spoke with Dr. Koblentz about a reason why the horsepox experiment got less attention. “First, part of the reason the H5N1 research made a big splash was because of the way it was presented to the scientific community and the public,” said Dr. Koblentz. “Ron Fouchier, who conducted one set of the mammal-transmissible H5N1 experiments in ferrets in the Netherlands, publicly emphasized how risky the research was. This publicity stunt generated headlines and attracted the attention of both the media and policymakers. Second, H5N1 is a well-known pathogen that causes approximately 50%-60% fatality among humans, and so, it was easy for even nonexperts to grasp the significance of making that virus transmissible between humans via the respiratory route, something the naturally occurring strain of H5N1 was not capable of doing.”

Dr. Koblentz noted that the horsepox research was not “hyped” by Tonix, the sponsoring company or the lead researcher, Dr. Evans. “The other factor is that horsepox itself is not dangerous to humans,” said Dr. Koblentz. “While it is closely related to smallpox and the techniques used to synthesize horsepox are directly applicable to the synthesis of smallpox, the risks posed by the synthesis of horsepox are farther over the horizon than the creation of mammal-transmissible H5N1.”

The horsepox experiment and the resulting biosecurity implications may not have resulted in a large ripple effect in the life sciences community; however, the truth is that this normalization is exactly why these conversations are vital. From the healthcare perspective, it may not seem like something we should worry about, but the direction of gene editing and dual-use research of concern is something that is intrinsically linked to public health. Nefarious outcomes of such experiments, regardless of the origin or intent, will inevitably make their way into an emergency department, urgent care, or worse, the community. Although we may not be seeing the implications today, as medical providers and healthcare workers, we must keep our ears to the ground, listening for these biotech advancements, and then thinking through what they mean for us tomorrow.