Thursday, January 12, 2012


One mistake away from a worldwide flu pandemic

<i>(Image: Frank May/UPPA/Photoshot)</i>
(Image: Frank May/UPPA/Photoshot)

Two labs have made lethal, highly transmissible versions of bird flu virus – do the risks of it escaping outweigh the benefits of the research?

AFTER a hard day at the lab, a biologist travels home on the subway. Later that evening his muscles start to ache and he notices that he is running a fever.
This is no ordinary bout of flu, though. The virus behind these symptoms is a highly transmissible variant of deadly H5N1 bird flu, and already people who shared his subway car have been exposed. It could now travel quickly around the world.
This is the alarming scenario that researchers are trying to prevent, now that two groups have brewed up variants of H5N1 that can spread between ferrets merely breathing the same air. "1918 flu would look like nothing if this really got loose," warns D. A. Henderson of the University of Pittsburgh, Pennsylvania, who led the fight to eradicate smallpox. "This is really serious."
In September, New Scientist reported that Ron Fouchier of the Erasmus Medical Centre in Rotterdam, the Netherlands, had found that just five mutations in two genes were enough to make a lethal variant of H5N1 with the ability to transmit readily between mammals - the missing factor that has so far kept down the number of people infected with H5N1. A second team, led by Yoshihiro Kawaoka of the University of Wisconsin-Madison, has made a subtly different virus with similar characteristics.
Debate is swirling over whether the experiments should have been carried out in the first place (see "We need to fix the holey biosafety net"), but one thing is clear: there is little room for complacency about the risks posed by naturally occurring H5N1 viruses, which might acquire similar mutations (see "The monster in the henhouse").
However, the studies hit the headlines when it emerged that advisers to the US government had asked Science and Nature, the journals planning to publish the work, to withhold key details to avoid providing a blueprint for would-be bioterrorists.
That risk needs to be taken seriously. But prior experience suggests that accidental viral releases pose a more immediate threat.
In the wake of the 2003 outbreak of SARS, some lab staff were accidentally infected by the SARS coronavirus in Singapore, Taiwan and China. In the most serious incident, the virus spread beyond a research institute in Beijing, and the mother of one of the researchers died. And in 1977, a mild strain of H1N1 flu was isolated in northern China, near the Russian border, and later spread worldwide. The virus almost certainly came from a deep-frozen lab sample, says Robert Webster of St Jude Children's Research Hospital in Memphis, Tennessee, who was involved in analysing the virus.
Avoiding a repeat performance with the new H5N1 viruses is a top priority. We don't know for sure that the viruses would behave the same way in people as in ferrets, but the assumption has to be that they do. If so, any release could lead to a devastating pandemic. "We have to be concerned to keep this thing locked down," says Webster.
What "locked down" means depends on who you ask, however. The highest level of containment for biological agents, known as BSL-4, demands stringent and expensive measures to prevent accidental releases. "I can't think of another infectious agent that deserves BSL-4 more than this one," says David Relman of Stanford University in California, who sits on the US National Science Advisory Board for Biosecurity, the panel that suggested the papers should be censored.
However, demanding BSL-4 would mean that most of the world's leading flu virologists would have to scale up their labs or move elsewhere. On the Erasmus Medical Centre's website, Fouchier's team summarises the "BSL-3 plus" procedures used in its experiments.
Webster and other flu researchers argue that it is important for top virologists to have access to the viruses, as we need to understand the mutations that could turn H5N1 into a mass killer. "The information we can obtain is really invaluable to make public health decisions," says Daniel Perez, a flu researcher at the University of Maryland in College Park.
Others question that assumption. Relman notes that there are likely to be multiple combinations of mutations that make wild H5N1 contagious in people, and asks whether the gains of studying these particular viruses in terms of improved surveillance for pandemic strains outweigh the risks of accidental release.
Before further research goes ahead, discussions need to take place on who should be able to work on the new viruses, and under what circumstances. Involving the nations most threatened by H5N1, such as China, will be crucial, as those who are excluded may be more likely to try and create similar viruses themselves.
With the viruses sitting in Fouchier's and Kawaoka's labs, the clock is ticking. "We can't spend years coming to a conclusion on this," says Michael Osterholm, who heads the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis. "We have got to have a plan for moving forward."

The monster in the henhouse

IN A few weeks, the world's top two scientific journals will publish work that shows how H5N1 bird flu could - perhaps - mutate to become a doomsday virus, going pandemic and killing millions of people.
The research was done to help us stop it doing that. But the only way that will happen is if we mount a concerted global effort to watch for these dangerous mutations in H5N1, which is now endemic in poultry in China, Indonesia, Vietnam, Bangladesh and Egypt, and widespread elsewhere.
Doomsday isn't upon us yet, however. The new work doesn't show what the modified virus will do in humans, says Richard Webby, a flu virologist at St Jude Children's Research Hospital in Memphis, Tennessee.
Moreover, a virus with only some of the required mutations might not survive well in the wild, making the fully evolved killer unlikely to emerge, at least without a lab's help (see main story). But with vast amounts of H5N1 in the world, "nature has time and numbers on its side", says Andrew Read at Pennsylvania State University in University Park.
Now we know mutations that can be dangerous, we can watch for them in poultry, where the virus is actively evolving. If the mutations show up, says Webby, "we kill lots of chickens".
For this to work, though, we need to look for H5N1. Yet "we have reduced surveillance", says Juan Lubroth at the UN Food and Agriculture Organization. "Resources for global and national intelligence have fallen, and this is of grave concern."
Some key countries are wary of international surveillance. In 2007, Indonesia stopped exporting H5N1 samples, protesting that it was supplying a rich vaccine industry for little return. China shares few samples, even though human deaths reveal its silent spread in the country's vaccinated birds.
Tortuous negotiations at the World Health Organization resulted in a deal in April last year in which countries agreed to share viruses if they were involved in the research and resulting benefits. The WHO is worried that the restrictions a US government committee has requested on the publication of the new work will send the wrong message. "It could potentially slow the sharing of viruses," says Keiji Fukuda, head of flu at the WHO.
"We hope that by the time the papers are published, we will have rules in place to allow legitimate scientists full access to the information," says Tony Fauci, head of the US National Institute of Allergy and Infectious Diseases, which is leading the debate. What these will be remains to be seen. Debora MacKenzie

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