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The horsepox virus could be the basis of an improved smallpox vaccine, more effective and with fewer side effects than the currently available vaccines.Colored etching, “Edward Jenner vaccinating patients in the Smallpox and Inoculation Hospital at St. Pancras: the patients develop features of cows,” by James Gillray / Wikicommons

Last year, when news broke that David H. Evans, a Canadian molecular virologist, and his colleagues made horsepox—the close cousin of smallpox—from scratch, people wondered: What for? Before it was eradicated, in 1980, in one of the major public health triumphs of the last several centuries, smallpox killed about a billion people. The worry about horsepox isn’t about horsepox itself—it doesn’t affect humans. It’s that nefarious actors, with enough expertise, could wield Evans’ work, since published in PlosONE in January, to make smallpox from scratch, and use it as a weapon. As almost all of the global population is unvaccinated, its reintroduction would be devastating.

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Naturally, this has caused some alarm in United States biosecurity and biodefense communities. The experiments reveal that our current biosecurity policies have some gaps. In fact, most of the debate around the new horsepox results has centered on these perceived risks. But what about the possible benefits? Evans said that the goal of his research was “to improve on current methods that protect the public from possible viral outbreaks.” The public health and academic research community has been largely silent on the central theory that Evans and his colleagues put forward: that the horsepox virus could be the basis of an improved smallpox vaccine, more effective and with fewer side effects than the currently available vaccines.

The smallpox vaccine currently held in the U.S. Strategic National Stockpile is effective and ready to be used in an emergency, but it can have serious side effects, including severe rashes and heart inflammation (myocarditis). These reactions make the vaccine less safe for vulnerable populations, such as people who have skin infections or who are immunocompromised (a more prevalent condition now than during the eradication years). The U.S. government has already invested in the advanced development of an additional, safer vaccine for people vulnerable to the standard one. But the side effects of a new vaccine can only be estimated through animal studies or indirect means, since there is no longer any circulating smallpox with which to do efficacy studies.

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Evans and his colleagues argue that horsepox is a good alternative to a smallpox vaccine. It has already been demonstrated to be effective when smallpox was naturally circulating, and it could have fewer side effects because it replicates more slowly. Some researchers posit that the original smallpox vaccine the 18th-century physician and scientist Edward Jenner used was based, in fact, on the horsepox virus.

Another biological threat we’re not well prepared for: monkeypox outbreaks.

These are compelling reasons to pursue horsepox research. In December, in a Health Security paper, we struck a pragmatic note. “It will be impossible to close off all avenues for nefarious misuse of gene synthesis, or misuse of biological materials more broadly,” we wrote. “As a result, we advocate for the implementation of policy, regulations, and guidance that will make illicit recreation harder, more burdensome, more detectable, and, thus, more preventable without having sweeping negative consequences for the research enterprise.” In March, in an mSphere paper, we further analyzed the biosecurity risks of the horsepox work and concluded that it would not substantially raise risks, particularly potential misuse by inexperienced actors.

The pox virus research and public health communities should be debating whether we need an improved smallpox vaccine, in addition to their focus on the dangers of new pox research. Critics of Evans’s paper assert that a stockpile of existing smallpox vaccine may make pursuing newer or improved vaccines cost-prohibitive, because there are other biosecurity priorities for the U.S. to invest in, and limited funds to develop and procure additional medical countermeasures. We acknowledge this. But broadening the scientific conversation around the merits of such therapeutics could only help us understand how appropriate and reliable they might be. Smallpox is likely to be a biosecurity threat for the foreseeable future—we should have a conversation about what the best vaccine would be to protect people against it.

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This horsepox story highlights another biological threat we’re not well prepared for: monkeypox outbreaks. While prior smallpox vaccination has kept monkeypox spread in check, people are no longer vaccinated against smallpox, and so aren’t protected against monkeypox, either. The ramifications for public health, should monkeypox become more readily transmitted between humans, hasn’t caught much attention. If monkeypox became more contagious, the public health community would need to deal with many of same challenges as those posed by reintroduced smallpox—namely, masses of unvaccinated people, the increase in immunocompromised populations, and potentially the challenge of mounting monkeypox clinical efficacy studies.

This conversation about dual-use research—work that could, in other words, be used toward good or ill—needs to continue so we can protect people from the harms that could come from the synthesis of viruses. But too much focus on the harms is detrimental.

Diane DiEuliis is a Senior Research fellow at the Center for the Study of Weapons of Mass Destruction at National Defense University. Her research areas focus on emerging biological technologies, biodefense, and preparedness for biothreats.

Gigi Gronvall is an immunologist by training and a Senior Scholar at the Johns Hopkins Center for Health Security and an Associate Professor in the Department of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health.

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