Smallpox killed its last victim almost exactly 40 years ago. Two years later the disease was declared officially eradicated. Although the chain of natural transmission was effectively broken decades ago, the disease remains a concern to medicine (1). Drawing attention to the recent U. S. Food and Drug Administration (FDA) approval for a drug treatment (1), an editorial published in Nature makes the case for continuing efforts to control or prevent smallpox. The reason is simple; no one can be certain the often deadly disease has claimed its final victims.
The Known Risks
Smallpox is eradicated, but is not truly extinct since viable stocks of the virus are being maintained in special facilities in the U. S. and Russia. Noting these conserved samples are essential for research and worried about possibilities the disease might return, officials have declined – repeatedly – to destroy them (1). The irony is that although maintaining virus stocks is deemed an essential public health safeguard, laboratory mishaps are a proven method for smallpox escape (1, 2).
Recounting the tragic story of medical photographer Janet Parker who was working at the Birmingham Medical School when she became infected with the smallpox virus, the Nature editors point out that her death was ascribed to laboratory mishap (1). Retrospective investigation revealed that faulty practices and ventilation allowed the virus to drift where she had been working one floor above the smallpox lab (1, 2). From 1963-1978, escapes from two separate, accredited labs in Great Britain resulted in 80 total smallpox cases with 3 fatalities (2). The fact that highly pathogenic agents have been released from biocontainment facilities (2) underscores the fact that maintaining smallpox stores in labs carries some, hopefully minimal, intrinsic risks.
The Potential Risks
Smallpox virus stocks have been used and stored over the years in multiple facilities. A surprising discovery of forgotten stored virus at the U. S. National Institutes of Health (NIH) reveals record keeping may have been lax and it may not be safe to assume all samples have been destroyed. In addition, the virus was weaponized at least once and viable stocks could still be held under the auspices of clandestine programs (1). Whether smallpox virus is re-introduced to the world through mishap or malice as a consequence of sanctioned work, terrorist plot or the actions of a single, perhaps demented, individual the outcome could be catastrophic.
A Look-Up and Cook-Up Future?
The emergence of synthetic biology provides a potent rationale for continuing robust efforts to prevent and treat smallpox. What were near-impossible fantasies about synthesizing viruses 15 years ago are racing toward routine implementation today. What miracles – and potential nightmares – will this fast-unfolding future bring us? Unfortunately, it could be a future where some genetic information itself poses a potential threat. One worry is that advances in the power and ease-of-use of new synthetic biology technologies may make it feasible for a person(s) unknown to take the already published smallpox genomic sequence information and use it as the recipe to cook up their own virus masterpiece.
But, Have We Gotten the Full Story?
There is something baffling about the smallpox story. Why have the authorities been so reluctant to destroy the last known stocks of this virus? Assuming for the moment that the U.S. and Russian caretakers could devise a way to assure their counterparts had complied faithfully and fully with orders, why hold on to this threat? Even if there are other virus stocks hidden away someplace, the smallpox virus itself is not necessary to conduct drug trials (1). In fact, smallpox virus is not needed to produce vaccines either. The modern vaccination process initiated and publicized by Edward Jenner (3), uses a relative that produces minor disease, cowpox (vaccinia) virus, to induce solid immunity to the far more dangerous smallpox (variola) virus. The immunization process employed today is basically the same as that Jenner used two centuries ago (4). As long as we have cowpox, we could make vaccines that would protect us against natural smallpox.
For the moment, for a variety of reasons, the persons in charge continue to maintain smallpox virus stocks. The risks posed by that decision are currently extremely low. In addition, vaccine stocks are in hand and new drugs are being developed. However, other than the fact that we will never be able to forget smallpox completely, we have only vague notions of what the future might bring.
(1) The Editorial Board. The Spectre of Smallpox Lingers. Nature 13 August 2018. https://www.nature.com/articles/d41586-018-05936-x
(2) Martin Furmanski. Threatened Pandemics and Laboratory Escapes: Self-fulfilling Prophecies. Bulletin of the Atomic Scientists, 31 March 2014. https://thebulletin.org/2014/03/threatened-pandemics-and-laboratory-escapes-self-fulfilling-prophecies/
(3) Greer Williams. 1959. The Virus Hunters. Knopf.
(4) The Centers for Disease Control and Prevention. https://www.cdc.gov/smallpox/vaccine-basics/index.html