August 30th 2016
Two great leaders of the battle against smallpox have passed away in the last 6 years - Frank Fenner, the chairman of the Global Commission for the Certification of Smallpox Eradication, in 2010, and in 2016, DA Henderson, who was director of the WHO Smallpox Eradication campaign, among other important leadership roles. They were both recognised as pivotal in the battle against smallpox, and shared the Japan prize for their achievements in smallpox eradication* in 1988. The passing of DA Henderson signals the end of an era, and the loss of a large body of lived experience and knowledge in a world where most doctors have never seen a case of smallpox, and the staff of public health agencies have no experience managing smallpox control. This has renewed discussion about smallpox and whether it still poses a threat to the world. There is speculation about smallpox re-emerging as corpses buried in Siberia thaw due to melting of the permfrost. Analogies have been drawn to an anthrax outbreak thought to have arisen from thawing reindeer corpses, however, the illness caused by anthrax is due to spores rather than to the bacteria itself, and the spores can remain dormant for long periods of time in the environment. Smallpox on the other hand is a virus, and whilst smallpox has been documented to survive for some time (up to years) in scabs on materials such as blankets if protected from ultraviolet light, it does not otherwise survive for long periods in the environment. The risk of viable smallpox virus emerging from the permafrost is low. Smallpox is a virus, and viruses require living cells in which to survive and replicate, so it is unlikely that living smallpox would re-emerge from dead human cells as corpses from the last century thaw. There is a greater threat of smallpox returning due to two other factors:
Retained stocks of live smallpox in laboratories after the eradication in 1977. This could be in the two known repositories, in the US or Russia, or in other locations which are unknown. Lab accidents could lead to smallpox. In fact, the last known case of small pox was due to accidental infection in a lab. Insider threat may also enable deliberate release of smallpox, and any clandestine labs harbouring smallpox would be purposely developing it as a weapon.
Synthetic biology – since 2002, scientists have been able to create viruses in a lab. The genetic sequence for smallpox is known, and quantum advances in science in the last 20 years mean that smallpox could be engineered in a lab. Existing stocks of smallpox in known or unknown locations could also be engineered and modified for increased infectiousness and pathogenicity. This kind of research was allegedly conducted in the Soviet Bioweapons program last century, and is now more accessible with new technology such as CRISPR-cas.
I have previously shown that when multifactorial risk-analysis is used that smallpox scores highly on the risk scale among category A bioterrorism agents. So, if there is a real threat of smallpox, what can be done about it? This can be separated into response to an epidemic of smallpox, and to mitigation and prevention of such an epidemic occurring. Most countries prepare to respond to a smallpox epidemic by stockpiling vaccines and drugs (such as the antiviral cidofivir) and having a disease control plan for epidemics. The question is about prioritisation of vaccine use in an epidemic, given there will likely not be stocks for the whole population. First responders such as health workers, paramedics, defence forces and emergency services should have the highest priority for vaccination. There are newer smallpox vaccines available, but the evidence around relative safety and efficacy is unclear. The greatest concern In 2016 is that the world's population has much lower immunity to smallpox than in 1977 when the disease was eradicated. At that time, levels of background immunity due to vaccination or natural infection in the population was higher. Anyone born after 1980 or so would have no immunity at all, and vaccine-induced immunity in older people would have waned. In addition, due to advances in medicine, there are many more people living with immunosuppression today than there were in 1977. As such, the impact of a smallpox epidemic today is likely to be very severe, and we may see much higher mortality than was seen in 1977.
Prevention is much more difficult. Infectious diseases do not recognise geographic boundaries, so experiments on dangerous pathogens done in one country can affect people in other countries. Global governance, legislation and systems to regulate synthetic biology, gain of function research, as well as coordinated approaches to laboratory security, are critical and yet patchy or inadequate. In 2016 the Biological Weapons Convention is being revised, and it is widely regarded as an outdated and unenforceable legislation. It assumes major players in biowarfare will be nation states, when there are clearly other players who could use biological weapons. There is an opportunity to consider the quantum changes in science and technology which have occurred and gaps in the BWC revisions (due in December 2016) related to this. Without such recognition, the BWC risks becoming obsolete.
Finally, we live in a world where organised crime, cybercrime and terrorism have coalesced, and trade in weapons, including biological weapons, occurs often on the dark web, under the radar of traditional crime surveillance methods. Trade in biological weapons may not be obvious, and may include selling of genetic sequences for viruses or laboratory reagents and materials for the conduct of genetic engineering research. Until the scope of such trade is defined, we cannot quantify the trade in biologicals on the dark web. It is widely recognised in the cybercrime space that technology has far outpaced our systems and legislation, and it is the same for biological weapons. These two areas are related because cybertechnology enables terrorism, including bioterrorism. The problem needs to be addressed from both angles – we need to be able to combat biosecurity risks on the dark web marketplaces where illegal transactions take place, and also in the realm of biological research. Our systems, legislation and capabilities have not kept pace with quantum changes in science, and this leaves us vulnerable in biosecurity.
In summary, the concerns about the melting permafrost may not be the most pressing concern around smallpox. As long as there are live stocks of smallpox in the world, as well as the ability to engineer smallpox in a lab, there is a real threat of re-emergence, whether by accidental or deliberate release. Crime and terrorism, themselves converging, are greatly enabled by advances in both cyber and biological technologies, and our ability to mitigate threats in biosecurity require quantum changes in our systems, approaches and governance structures.
* see my explanation of eradication vs elimination, and contrasting smallpox with measles.
Interested in more? Do our course, Bioterrorism and Health Intelligence this summer, November 28th 2016
Raina MacIntyre is the Director of ISER, a Centre for Research Excellence dedicated to epidemic response.
ISER produces Epiwatch, a rapid outbreak intelligence service and features the ISER Academy, dedicated to solving wicked problems in biosecurity by bringing together stakeholders from different responder sectors.
Image source: Wikipedia