- The 1918 flu virus spread across the world in three months
and killed at least 40 million people. If it escaped from a lab today,
the death toll could be far higher. "The potential implications of
an infected lab worker ñ and spread beyond the lab ñ are
terrifying," says D. A. Henderson of the University of Pittsburgh,
a leading biosecurity expert.
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- Yet despite the danger, researchers in the US are working
with reconstructed versions of the virus at less than the maximum level
of containment. Many other experts are worried about the risks. "All
the virologists I have spoken to have concerns," says Ingegerd Kallings
of the Swedish Institute for Infectious Disease Control in Stockholm, who
helped set laboratory safety standards for the World Health Organization.
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- Work on the 1918 flu virus is not the only worry. Some
experiments with bird flu have also been criticised as dangerous (New Scientist
print edition, 28 February 2004).
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- Kallings and others are calling for international discussions
to resolve the issues related to such work. "It is time for influenza
scientists to find a consensus on containment," she says. John MacKenzie
of the University of Queensland in Australia, who investigated how the
SARS virus escaped from high-level containment labs in east Asia on three
occasions after lab workers became infected, agrees. "A meeting would
be beneficial."
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- Gene sequencing
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- The researchers working on the 1918 virus say their work
is vital to understand what changes make flu viruses dangerous. So far
five of the 1918 flu virusís eight genes have been sequenced, using
fragments retrieved from victims of the pandemic. Several teams have added
one or more of these genes to modern flu viruses, or plan to ñ in
effect partially recreating the long-vanished pandemic virus.
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- The latest work was done by Yoshihiro Kawaoka at the
University of Wisconsin at Madison. His team showed that adding the 1918
gene for the surface protein haemagglutinin to modern viruses made them
far deadlier to mice. The researchers also found that people born after
1918 have little or no immunity.
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- The team started the work at the highest level of containment,
BSL-4, at Canada's National Microbiology Laboratory in Winnipeg. Then they
decided the viruses were safe enough to handle at the next level down,
and did the rest of the work across the border in a BSL-3Ag lab in Madison.
The main difference between BSL-4 and BSL-3Ag is that precautions to ensure
staff do not get infected are less stringent: while BSL-4 involves wearing
fully enclosed body suits, those working at BSL-3Ag labs typically have
half-suits.
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- Kawaoka told New Scientist that the decision to move
down to BSL-3Ag was taken only after experiments at BSL-4 showed that giving
mice the antiviral drug oseltamivir (Tamiflu) in advance prevented them
getting sick. This means, he says, that if all lab workers take oseltamivir
"they cannot become infected".
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- Contradictory results
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- Yet this assumes that the mouse results apply to humans.
And the findings have not been published. In similar experiments, Terrence
Tumpey's team at the US Department of Agriculture's poultry research lab
in Athens, Georgia, got quite different results: they found that mice given
oseltamivir still got sick and 1 in 10 died. It is not clear why Kawaoka's
mice fared better.
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- What is more, all the safety precautions are aimed at
preventing escape, not dealing with it should it occur. If any of Kawaoka's
lab workers are exposed to the virus despite all the precautions, and become
infected despite taking oseltamivir, the consequences could be disastrous.
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- "I experienced disbelief... regarding the decision
to relocate the reconstructed 1918 influenza strain from a BSL-4 facility
to a BSL-3 facility, based on its susceptibility to antiviral medication,"
Ronald Voorhees, chief medical officer at the New Mexico Department of
Health, wrote on ProMED-mail, an infectious diseases mailing list.
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- Yet Kawaoka's decision does comply with the US National
Institutes of Health guidelines for BSL-3 agents: those causing "serious
or lethal human disease for which preventive or therapeutic interventions
may be [its italics] available". In fact, he is considered unusually
cautious. "Kawaoka should be applauded for using BSL-4 at all,"
says Richard Webby, a flu researcher at St Jude's Children's Hospital in
Memphis, Tennessee.
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- Exposing monkeys
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- By contrast, the team in Georgia, the first to experiment
with genetically engineered 1918 viruses, did all its work at BSL-3Ag.
Meanwhile, Michael Katze at the University of Washington at Seattle is
planning to expose monkeys to aerosols of 1918-type viruses at BSL-3, a
step down from BSL-3Ag. The recent SARS escapes were from BSL-3 labs.
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- "We would have to do any such work at BSL-4,"
says John Wood of the UK's National Institute for Biological Standards
and Control. In the US, the differing standards applied by different groups
are due to the fact that experiments on engineered viruses such as the
1918 flu are approved on a case-by-case basis by Institutional Biosafety
Committees (IBCs), composed of local scientists and officials. Critics
say these are free to interpret the official guidelines in a way that suits
them.
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- "There is no effective national system to ensure
consistency, responsibility and good judgement in such research,"
says Edward Hammond of the Sunshine Project, a biosecurity pressure group
in Austin, Texas. In a review of IBCs published this month, he found that
many would not provide minutes of recent meetings as required by law.
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- He says the IBC that approved the planned 1918 flu study
at the University of Washington considered only one scenario that could
result in workers being exposed to airborne virus ñ the dropping
of samples. Its solution: lab workers "will be trained to stop breathing".
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