The risk of smallpox
Here’s an interesting editorial from Science magazine, detailing the continuing saga of whether science should maintain the remaining stores of viable smallpox (variola) virus. Laboratories in the US at the Centers for Disease Control, and the State Research Center of Virology (Vector) in Russia are the only two locations which currently maintain viable stocks of the smallpox virus.
Smallpox was eradicated due to the global effort of countless health care workers during the 1970’s. I recently finished Richard Preston’s Demon in the Freezer, which detailed the politics, logistics, and the personal stories of this tremendous project. After the last wild case of variola major, the more deadly form of the disease, was recorded in 1975, there was only one additional death due to the disease by a hospital worker in the United Kingdom who acquired it in a laboratory accident in 1978. Mass vaccination of the United States population ceased in the early 1970’s, but due to the limit on protection afforded by the vaccine, the majority of the world’s population currently has very low to non-existent immunity to smallpox.
This poses an interesting question, which is addressed in the Science editorial linked at the top: since there is no “wild” smallpox anywhere in the world, and therefore no risk of acquiring the disease via the means by which it has historically infected humans, is there any benefit of maintaining virus stocks at the CDC and at Vector in Russia? The has requested that the United States and Russia destroy the remaining stocks of virus. The governments of the US and Russia both currently would like to maintain their virus stocks, and have convinced the World Health Organization to table the discussion until after 2014.has for about 3 decades maintained that the risks of maintaining these stocks outweighs any benefits, and
The controversy ultimately boils down to bioterrorism, and society’s preparedness against a deliberate release of a deadly infectious agent. Such an event has already occurred, and smallpox poses a set of concerns that were not applicable during the anthrax scare. First and foremost is this: smallpox is highly contagious, is easily passed from individual to individual, and can rapidly pass throughout a population. Anthrax on the other hand is not contagious, and requires exposure to an environmental source for infection. The rationale towards maintaining the smallpox stocks at the CDC is that there is a positive medical benefit to be obtained from research on the virus, as we identify potential therapeutics for smallpox infection. The great worry of course is that samples of the virus might be misappropriated or lost from these known stockpiles, and used in a terror event.
Preston’s book gives a very approachable summary of the possible medical benefits of research on smallpox. The main argument put forth by the US government for maintaining the virus stocks is that we have a poor understanding of the cellular mechanisms by which smallpox is able to cause the tremendous damage that it does in the human body. Recall that the last human case of smallpox was in 1978, and cellular and molecular medicine have advanced tremendously since that time! Furthermore, scientists have little understanding of the mechanisms by which the immune system reacts and develops immunity to the smallpox virus. Research into the infection mechanism can therefore lead to developing novel antiviral therapies, which in turn would enable us to better react to a smallpox outbreak.
The problem with this line of thinking (as nicely detailed by Preston, and I concur with this reasoning) is that smallpox has no efficient mode of replication outside of the human body. Infection experiments have been done by the CDC and the US Army Medical Research Institute with non-human primates, and while successful, they have not produced a clear correlation with the infection process in humans. Significantly, it requires many orders of magnitude more virus to infect a non-human primate than it does a human, driving home the point that smallpox in a macaque is very different from smallpox in a human. Not surprisingly, there is little in the medical literature suggesting that a suitable animal model for the study of smallpox infection is imminent. If we cannot study infection appropriately in an animal, then our recourse is to study infection in a humanized cell culture system. While this can give us some information about the cellular response to infection to variola, it will not help us to learn anything about the response of the whole body to infection.
So what ultimately are the dangers of smallpox? At present, the world population is approximately 6.7 billion, and the vast majority (greater than 99%) of those people are going to be susceptible to smallpox infection. The only people in the United States with current immune protection to smallpox infection are some members of the military, who are considered to be at risk to a bioterrorism attack. Individuals born before the late 1960’s were actively immunized, but that immunity is not going to be very effective anymore. Preston’s book argues that the security of the virus stocks at the CDC is quite effective, but admittedly is conjecture on his part. Security at the corresponding institution in Russia is complete conjecture, which leaves us with the very real possibility that samples of the virus exist outside of these known locations.
It may not require actual smallpox virus stocks to initiate a terror event with smallpox however. The genome of an infectious isolate of variola major (the more significant form of the disease) is freely available via a quick search at Genbank. Variola is a complex virus, with a relatively large genome, but de novo synthesis of the genome using standard undergraduate molecular biology techniques is not an unrealistic process. Furthermore, virulence of many viruses can be affected by the introduction of novel sequences, making the resultant agent a much more serious risk. Two decades ago this scenario was the topic of science fiction; today we live in an age where a completely novel bacterium can be constructed via chemical synthesis of its DNA in the laboratory.
The World Health Organization will continue to push for remaining viable stocks of the virus to be destroyed when the topic comes back up for discussion in a few years. The major outcome from that move will likely not be to reduce the risk of a bioterrorism event due to loss of the agents from the US or Russia, but to more firmly cement the criminality of possession of the virus.