US develops lethal new viruses
Thu Oct 30 16:22:57 2003
US develops lethal new viruses
19:00 29 October 03 Exclusive from New Scientist
A scientist funded by the US government has deliberately created an extremely
deadly form of mousepox, a relative of the smallpox virus, through genetic
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 similar way.
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
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
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 antibody production.
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, however.
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 containment.
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
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.
Debora MacKenzie, Geneva
The World's No.1 Science & Technology News Service
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