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Saturday, February 12, 2011

Smallpox virus: crunch time for the fate of a global killer

Smallpox has long been eradicated but the virus still exists at two high-security labs. Should these stocks now be destroyed?

Robin McKie and Gabriel Stargardter
Twenty miles south-east of Novosibirsk, in Siberia, several dozen concrete buildings have been erected outside the town of Koltsovo. The settlement is ringed with triple rows of barbed wire fences. Video cameras and motion sensors monitor any activity near the wires while soldiers from an elite Russian army unit patrol its perimeter.

This is Russia's State Research Centre of Virology and Biotechnology – or Vector, as it is usually known. Frozen in winter, when temperatures plunge below -30C, and then scorched in summer, when the heat routinely rises above 30C, the place is as unwelcoming as you could imagine. Given its name, location and a high-security protection, Vector would make an ideal setting for a James Bond film.

This would be a fitting accolade, for Vector contains a number of unsettling scientific secrets, with the most sinister being housed in bio-containment laboratory P-4, in Building 6. Here a small storage plant, chilled by liquid nitrogen, holds phials of one of the deadliest pathogens known to medical science: the smallpox virus.

Smallpox killed the Egyptian pharoah Ramses V in 1145 BC and Tsar Peter II of Russia in 1730 and was responsible for an estimated 300–500 million deaths in the 20th century alone; only in 1980 was it declared eradicated by the World Health Organisation following a series of global vaccination programmes. But smallpox – with its once dreaded symptoms of blistered skin, lesions, delirium and fever – does survive in two places on Earth: at Vector and at another high-security laboratory, at the Centre for Disease Control in Atlanta, USA.


At the Russian and American units, scientists have continued to study the smallpox virus for the past decade. However, these last repositories are now under threat. In May, the World Health Assembly – the decision-making body of the WHO – will be asked to set a date by which these collections should be destroyed. If agreed, the move would result in the extinction of one of the deadliest ailments to have afflicted our species.

Previous assemblies have delayed moves to have these last smallpox stocks destroyed. Nevertheless, it is expected that a decision will be taken this time: either to eradicate the virus or to save it.

The issue may seem straightforward: why should humanity keep phials of a deadly virus that it went to such pains to eradicate and which could trigger a horrific epidemic in the event of an accidental release? This point is stressed by the many doctors and scientists who back the call for the phials' destruction. It is time to wipe this scourge from our planet, they say.

Such views are not shared by all scientists, however. An opposing group claims that disposal of the CDC and Vector's smallpox stocks would be a disaster, arguing that the world needs these samples in order to develop new drugs against the disease should it one day reappear, either accidentally or intentionally. Those stocks could be our saviour, they claim. The World Health Assembly vote is going to trigger an intense scientific battle.

A detailed look at both sides is illuminating, starting with those researchers – including many senior scientists and defence officials in Russia and the US – who say it would be a calamity if the smallpox pathogen was destroyed. These virus supporters, who are known as "retentionists", argue there is a strong prospect that smallpox samples may already have been obtained by terrorist groups and that the Vector and CDC stocks will therefore be needed to help defend the world from bio-terror attacks. To back this point, the Russians say Iran made several attempts in the 1990s to recruit some of their Vector scientists – efforts that may have been successful in a couple of instances.

American scientists and officials take a similar view. Before 9/11, the US supported the destruction of smallpox stocks, but it now takes the risk of an attack seriously. Last month, an unnamed US scientist – who was also a former UN inspector – told the Wall Street Journal that inspections in Iraq in 2003 and 2004 provided some "credible intelligence that suggests it [the virus] was there". Hence the need to retain smallpox samples and to continue testing drugs and vaccines that could counter the disease if a release occurred.

This argument has powerful supporters. Last month, an editorial in the science journal Nature argued that the danger posed by the use of smallpox as a terrorist weapon should not be ignored. The vaccination programmes of the last century, although saving countless lives, has – paradoxically – left the world's population dangerously exposed. "Smallpox would be an effective weapon – it spreads easily and kills almost one-third of the people it infects," the editorial states. "Furthermore, the triumph of smallpox eradication after widespread vaccination in the 1960s and 1970s means that some 40% of the world's population has no immunity today." In short, we're vulnerable and care is needed to ensure the protection of billions of individuals now defenceless against a new smallpox epidemic.

There is a further argument, put forward by retentionists. The smallpox virus is such a deadly pathogen, it acts as a Rosetta stone for understanding the immune system, they say. This point is stressed by Dr Inger Damon, head of the CDC's poxvirus section. She is one of only 10 scientists who has access to the centre's smallpox samples – housed in a high-security laboratory that can only be reached using electronic security cards and retinal scanners – which she uses to study diagnostic tests, anti-virus therapies and new vaccines against the virus. "There is considerable uncertainty about possible undisclosed virus stocks that might exist – about what might be out there and about the dangers of smallpox being used as an agent of terrorism," she says. "That is why we need to keep these stocks and to keep studying them."


However, other scientists disagree and argue the virus should be wiped out completely. This camp – known as the "destructionists" – argue that there is little new information to be gained from continued research on the smallpox virus. Experiments on pathogens have yielded all the information that can be gleaned. At the same time, keeping samples alive maintains a constant risk of an accidental release that could have disastrous consequences.

An example is provided by the accidental release of the variola virus, which causes smallpox, from a research laboratory at Birmingham university in 1978. Janet Parker, a medical photographer, was infected and subsequently died, though not before transmitting the disease to her mother. In the end, the outbreak was contained, although the head of the microbiology unit, Professor Henry Bedson, subsequently killed himself, leaving a note apologising for his role in the incident.

However, there is another, more important reason for eradicating the world's last smallpox stocks, argues DA Henderson, head of the WHO's eradication campaign and a former leading US expert on bioterrorism. Once virus stocks are destroyed, "any lab, scientist or country found to have the virus after the date of destruction is de facto guilty of very serious crimes against humanity," he says.

This argument is backed by security expert Jonathan Tucker of Darmstadt University. "If the authorised stocks of the virus were eliminated, it would become possible to draw a clear red line and brand any possession, synthesis or hostile use of the variola virus as a crime against humanity, punishable with the most severe economic, political and military sanctions," he states.


How these arguments will influence the World Health Assembly is difficult to assess. It is possible it may vote for destruction but for the US and Russia to refuse. Another scenario might see an agreement to destroy most samples, but retain a handful as last resorts. (CDC has 451 samples at present, Vector 120.) Or it may simply agree to the status quo.

In any case, eradication of the US and Russian samples would not necessarily wipe out smallpox for eternity. Its genome is known and scientists, using the latest in DNA technology, could recreate the virus from scratch, a point stressed by Dr Inger Damon. "Biology has now advanced to the stage where it is no longer inconceivable that one could put together a virus as large as the smallpox variola using synthesised nucleic acids," she says. "This is all the more reason, I believe, for keeping the natural variety in safe containment for future study."
http://www2.cdc.gov/nip/isd/spoxclincian/contents/printable_version.htm
http://www.life.com/image/50702576
http://www.upmc-biosecurity.org/website/focus/agents_diseases/fact_sheets/smallpox.html
http://www.guardian.co.uk/society/2011/feb/13/smallpox-virus-vector-health-terror
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