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Subject: Interesting
Date: Thu, 21 Oct 2004 20:22:43 EDT



Experts fear escape of 1918 flu from lab 21 October 04
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 – and
spread beyond the lab – are terrifying,” says D. A. Henderson of the University
of Pittsburgh, a leading biosecurity expert.
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.
Work on the 1918 flu virus is not the only worry. Some experiments with bird
flu have also been criticised as dangerous .
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.”

Gene sequencing
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 virus
’s 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 – in effect partially recreating the long-vanished
pandemic virus.
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.
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.
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”
.

Contradictory results
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.
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.
“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.
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.

Exposing monkeys


















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.
“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.
“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.
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 – the dropping of samples. Its solution: lab
workers “will be trained to stop breathing”.

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