Smallpox: Threat Resurrected

Health ministers from around the world are gathering this month at the Geneva headquarters of the World Health Organization (WHO) for their annual meeting, the World Health Assembly. On the agenda will be a dilemma that has dogged decision-makers for decades - whether and when to destroy the last remaining stocks of the smallpox virus,which are still being held in high-security laboratories in Russia and the United States (US) more than thirty years after the disease was erased from the planet.

The World Today
Published 1 May 2011 Updated 23 March 2020 4 minute READ

After smallpox was declared conquered in 1980, it had been accepted that the virus samples would be destroyed. The first deadline recommended by a WHO expert advisory committee was 1993, but the World Health Assembly has repeatedly delayed destruction after the US expressed fears in the mid- 1990s that the virus may exist outside the two designated laboratories and could be used as a military or terrorist bioweapon.

The main opponents of destruction, known as retentionists, argue it is necessary to retain the virus samples for research aimed at developing safer vaccines, new drugs and diagnostic tests to be used in the event the disease is reintroduced. Meanwhile, proponents of destruction, or destructionists, argue that the risk of laboratory accidents posed by continued research on the virus is too high. Either way, if the virus is reintroduced, the impact could be devastating, given thatmost people born after 1980 have not been vaccinated against the disease and that immunity wanes over time.

Pressure is mounting for the health ministers to set a new deadline for destruction at this year’s World Health Assembly, on the basis that the virus is no longer needed for research, while the risk of a laboratory accident that could unleash the virus remains. There have been three smallpox research laboratory accidents since the mid 1970s, and one was fatal.

Devastating Scourge

An incurable and contagious airborne infection, smallpox was one of humankind’s most ancient and devastating plagues. For centuries, it swept across continents in repeated epidemics, striking fear into people around the world, killing about thirty percent of its victims and leaving most of its survivors disfigured, and many blinded. Some experts estimate it killed about three hundred million people during the 20th century alone. It was characterised by a rash of pea-sized pustules that would erupt under the skin and spread, sometimes covering almost the entire body.

Smallpox was the first disease that humankind had eradicated, and remains to this day the only disease we have wiped out. By 1953, when the idea of eradication was first seriously discussed at the World Health Assembly, many industrialised countries had managed to contain the disease with vaccination, and in 1959, the member states of the WHO voted unanimously in favour of trying to stamp it out worldwide. Seven years later, with many developing countries struggling to beat the virus, governments allocated funds for the WHO to coordinate an intensified global effort. Eleven years after that, the last natural case of infection occurred in Somalia in 1977.

In 1981, just after the disease was certified eradicated, four countries declared theywere holding stocks of the virus - South Africa, Britain, the US and the Soviet Union. Britain transferred its virus collection to the US in 1982 and South Africa destroyed its stocks the following year. The WHO had previously conducted a survey of laboratories around the world to determine who was holding the virus and had urged countries to either destroy or consolidate their stocks. However, because the survey was voluntary, undeclared holdings - either deliberate or unwitting - could not be ruled out. The World Health Assembly in 1984 designed two government-owned laboratories - the Russian Federation’s virology institute in Koltsovo, Siberia, and the Centers for Disease Control and Prevention in Atlanta in the United States - as the sole authorised repositories of the remaining virus.

In 1990, the WHO’s advisory committee on orthopoxvirus infections recommended that the virus stocks be destroyed by the end of 1993 after the DNA of representative strains had been sequenced, and in preparation, scientists began the DNA sequencing.

Reluctance

The recommendation sparked debate and the orthopoxvirus advisory committee re-examined it again in 1994. Besides the risk of hidden or forgotten samples reintroducing the disease, some proponents of retention expressed fears that the virus could be released if corpses of smallpox victims buried in the permafrost of Siberia thawed as a result of global warming.

However, the committee confirmed the destruction recommendation unanimously, on the back of a review that concluded that the potential risks of the virus being released outweighed the potential benefits to be gained by retaining the stocks.

The recommendation came before the World Health Assembly in 1996, but the Assembly instead adopted a US-supported resolution that delayed destruction until June 1999 so that research could continue, and required a further vote in May 1999 to confirm the decision to destroy. The virus got a stay of execution again in 1999 after a report by the US Institute of Medicine recommended more research on the virus, especially to develop two new drugs to treat the disease, arguing that they are needed because the existing vaccine could be dangerous for people with certain conditions, such as HIV and atopic dermatitis, and because of the possibility that the virus could mutate, rendering existing drugs less effective.

The argument did not convince all, but after a long debate, the World Health Assembly decided to allow research to continue for three more years and to revisit the issue in 2002. In 2002, the World Health Assembly again gave the virus a reprieve, as some key experiments in the smallpox research programme had yet to be completed. However, while the previous resolutions authorised research to continue for a limited period of time before health ministers were required to revisit the timeline for destruction, the 2002 resolution authorised research to continue indefinitely, until all its goals had been achieved.

At the 2006 World Health Assembly, the African bloc of countries, supported by some other developing countries, pressed for a new deadline to be set. The discussion was postponed until the following year, when countries asked the WHO to conduct a comprehensive review of the results of the smallpox research programme, to help them reach consensus on the timing of virus destruction at the 2011 World Health Assembly.

WHO commissioned a review of the research conducted between 1999 and 2010 and asked an advisory group of independent experts to use it to assess whether more research using the virus stocks is necessary. The group, whose report was published in December and is expected to be influential in this month’s discussions, concluded that although the development of a new vaccine, and perhaps another drug, should continue, there is no longer any scientific or public health reason to hold onto the virus other than to satisfy the requirements of drug regulators. The report recommended that researchers and regulators cooperate to reconsider the requirements and devise a way around the problem, in preparation for destruction of the virus stocks.

DNA Threat

In an analysis published earlier this year, security expert Jonathan Tucker, Professor of Science and Technology for Peace and Security at Darmstadt University of Technology, Germany, and author of Scourge: The Once and Future Threat of Smallpox, notes that complicating the issue is the fact that even if the virus stocks were destroyed, it would not necessarily mean smallpox would never been seen again. The smallpox genome has been sequenced and it is now technically feasible for scientists to recreate it using modern DNA technology.

Both sides of the debate have used this possibility to argue their case. Retentionists contend that if the virus can be synthesized from scratch, the risk of an attack is higher and there is even more reason to carry on with research so that new countermeasures can be developed. However, destructionists argue that we have enough drugs, vaccines and diagnostic tests already and that the ability to recreate the virus in a laboratory makes it even more important that the official stocks are destroyed so that possession of the virus - whether natural or engineered - can be banned and prosecuted as a crime against humanity. Retentionists question in turn whether the official stocks need to be destroyed in order for unauthorised possession to be branded a crime against humanity.

A Way Through

Tucker argues that tensions over the issue could come to a head at this year’s World Health Assembly. He notes that developing countries in Africa and Asia, who fear they will bear the brunt of any accidental reintroduction of the virus, are becoming impatient with the lack of progress, and see the issue more as one of public health than national security. Besides wanting the virus destroyed for safety reasons, they also question the wisdom of the investment when other infectious diseases posemore immediate challenges for them.

Tucker raises the point that if the Assembly fails to reach consensus, it could opt for a majority vote - as it did in 1966 to launch the intensified campaign against smallpox. He argues that to avoid a diplomatic confrontation with potentially serious consequences, the US should accept a deadline for virus destruction. If this proves to be untenable because of resistance from Russia or other countries, the Americans should negotiate a compromise. He proposes that such a deal could entail the reduction of the virus stocks, with research on the remaining samples continuing until two new drugs have been developed for emergency use, which avoids the current problem related to standard regulatory approval. He also suggests that the package include a ban on the genetic engineering of the virus and measures to increase developing country access to any of the drugs and vaccines resulting from the research, such as royalty-free manufacturing licenses and funds to establish a WHO-controlled drug stockpile. He argues that such assistance would generate good will and might be seen by developing countries as a reasonable compromise.

Smallpox eradication was one of the greatest triumphs of public health, but it remains a threat. More than forty years ago, the world united behind a common objective and succeeded. Nations are gathering again this month to tackle the legacy of smallpox, but whilst they are still united in their desire to combat the threat, they are this time divided over the method. It remains to be seen whether this year is the year they can break the deadlock.