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Smallpox—A Nightmare We Cannot Shake

There is a new treatment for this old disease, so why are we still worried?

There are some things in public health that seem to leave a mark forever. The Black Death, smallpox contaminated blankets used as a weapon, Amerithrax, the Tuskegee syphilis study, etc. Public health is filled with wonderful and horrifying moments alike and the truth is that we do not get many moments to truly celebrate on a global level. Outbreaks may end, but the act of completely eradicating a disease? That’s something we’ve been striving toward for centuries, and with smallpox, we hit the goal in 1980. The eradication is considered one of the greatest public health accomplishments in history. A monumental global effort, it is something we remember as a proud moment in public health. Given the success of eradication, it begs the question: Why does the nightmare of smallpox still linger?

In July 2018, the antiviral TPOXX was approved as the first ever treatment for smallpox. It may seem odd that treatments for an eradicated disease are still being developed, but the truth is that there is still a chance smallpox could resurface. That may seem a bit “doomsday-ish” but here are a few reasons why we should take the threat of smallpox seriously.

Firstly, there are ongoing debates regarding the destruction of the remaining stockpiles. The 2 remaining stockpiles of the last remnants of the virus are housed at the US Centers for Disease Control and Prevention and the Russian facility, VECTOR. Inherently, the presence of these samples poses a biosecurity risk, increasing the chance for a nefarious actor to steal the stock, and a biosafety risk through a chance laboratory accident, and more.

Secondly, recent advances in synthetic biology have many individuals in the health care and biotech industry concerned that DIY biohacker could reconstitute the smallpox virus. This is not a new concern, as researchers within the biosecurity community have been looking at advances in synthetic biology with increasing concern since DIY CRISPR kits were being sold online and the barriers to genome editing became lower. This was further fueled by the 2017 publishing of a paper by researchers in Canada who synthesized the horsepox virus with $100,000, several months in the lab, and mail-ordered DNA. The lack of barriers throughout the project and publication was deeply disturbing and ultimately brought forth a fervor of concern within the biosecurity and life sciences community.

Thirdly, a frozen smallpox victim could be unearthed in thawed permafrost. Although that sounds like something out of a science-fiction movie, it poses a significant threat. An outbreak of anthrax in Russia is thought to have been the result of thawing permafrost and ancient viruses have been found in the same fashion. It is not unrealistic that a corpse, long since forgotten, could be found with a viral passenger.

Lastly, there is the stark reality that most individuals in the United States are unvaccinated and vulnerable to the smallpox virus as routine vaccination stopped in 1971 after the risk of importation of the virus was decreased in the 1960s. The virus was declared eradicated around the world in 1980. Although the US government stockpiles smallpox vaccine, most individuals are still inherently vulnerable. That is the tricky part about smallpox eradication—it is an amazing step for public health and human lives, but it also comes with a burden future generations will carry.

As such, smallpox and the actuality of its threat is a complex topic for which there is a spectrum of answers. Most medical providers alive today have not seen a case of smallpox outside of a textbook. For this very reason (and all those listed previously) I advise clinicians to take a moment and remind yourself about the disease. Remember the importance of isolation precautions and take 5 minutes to refresh your memory on what smallpox looks like in a patient before the never event of an outbreak becomes a reality.