A scientist funded by the US government has deliberately created an
extremely deadly form of mousepox, a relative of the smallpox virus,
through genetic engineering.
The new virus kills all mice even if they have been given antiviral drugs as well as a vaccine that would normally protect them.
The work has not stopped there. The cowpox virus, which infects a
range of animals including humans, has been genetically altered in a
The new virus, which is about to be tested on animals, should be
lethal only to mice, Mark Buller of the University of St Louis told New Scientist. He says his work is necessary to explore what bioterrorists might do.
But the research brings closer the prospect of pox viruses that
cause only mild infections in humans being turned into diseases lethal
even to people who have been vaccinated.
And vaccines are currently our main defence against smallpox and its
relatives, such as the monkeypox that reached the US this year. Some
researchers think the latest research is risky and unnecessary.
"I have great concern about doing this in a pox virus that can cross
species," said Ian Ramshaw of the Australian National University in
Canberra on being told of Buller's work.
Ramshaw was a member of the team that accidentally discovered how to make mousepox more deadly (New Scientist, 13 January 2001). But the modified mousepox his team created was not as deadly as Buller's.
Since then, Ramshaw told New Scientist, his team has also
created more deadly forms of mousepox, and has used the same method to
engineer a more deadly rabbitpox virus.
But this research revealed that the modified pox viruses are not
contagious, he says. That is good news in the sense that these viruses
could not cause ecological havoc by wiping out mouse or rabbit
populations around the world if they escaped from a lab.
However, this discovery also means some bioterrorists might be more
tempted to use the same trick to modify a pox virus that infects
humans. Such a disease, like anthrax, would infect only those directly
exposed to it. It would not spread around the world and rebound on the
attackers. But there is no guarantee that other pox viruses modified in
a similar way would also be non-contagious.
Ramshaw's team made its initial discovery while developing
contraceptive vaccines for sterilising mice and rabbits without killing
them. The researchers modified the mousepox virus by adding a gene for
a natural immunosuppressant called IL-4, expecting this would boost
Instead, the modified mousepox virus was far more lethal, killing 60
per cent of vaccinated mice. The addition of IL-4 seems to switch off a
key part of the immune system called the cell-mediated response.
Now Buller has engineered a mousepox strain that kills 100 per cent
of vaccinated mice, even when they were also treated with the antiviral
drug cidofovir. A monoclonal antibody that mops up IL-4 did save some,
His team "optimised" the virus by placing the IL-4 gene in a
different part of the viral genome and adding a promoter sequence to
maximise production of the IL-4 protein, he told a biosecurity
conference in Geneva last week.
Buller has also constructed a cowpox virus containing the mouse IL-4
gene, which is about to be tested on mice at the US Army Medical
Research Institute of Infectious Diseases at Fort Detrick, Maryland.
Cowpox infects people, but Buller says the IL-4 protein is
species-specific and would not affect the human immune system. The
experiments are being done at the second-highest level of biological
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Ramshaw says there is no reason to do the cowpox experiments, as his
group's work on rabbits has already shown the method works for other
pox viruses. While viruses containing mouse IL-4 should not be lethal
to humans, recombinant viruses can have unexpected effects, he says.
"You'd hope the combination remains mouse-specific."
Why his group's engineered viruses are not contagious is a mystery,
he says. It is not, for instance, because the host dies faster than
usual, taking the virus with it. But his findings could explain why pox
viruses containing IL-4 have never evolved naturally, even though the
viruses frequently pick up genes that affect their host's immunity.
Despite the concerns, work on lethal new pox viruses seems likely to
continue in the US. When members of the audience in Geneva questioned
the need for such experiments, an American voice in the back boomed
out: "Nine-eleven". There were murmurs of agreement.