Killer virus: An engineered mouse virus leaves us one step
away from the ultimate bioweapon
Rachel Nowak, Melbourne
A virus that kills every one of its victims, by wiping out part of
their immune system, has been accidentally created by an
Australian research team. The virus, a modified mousepox,
does not affect humans, but it is closely related to smallpox,
raising fears that the technology could be used in biowarfare.
The discovery highlights a growing problem. How do you stop
terrorists taking legitimate research and adapting it for their
own nefarious purposes?
The Australian researchers had no intention of producing a
killer virus. They were merely trying to make a mouse
contraceptive vaccine for pest control. "But it's a good way to
show how to alter smallpox to make it more virulent," says Ken
Alibek, former second-in-command of the civilian branch of the
Soviet germ-warfare programme.
Ron Jackson of CSIRO's wildlife division and Ian Ramshaw at
the Australian National University, both in Canberra, inserted
into a mousepox virus a gene that creates large amounts of
interleukin 4. IL-4 is a molecule that occurs naturally in the
body. As part of a study aimed at creating a contraceptive
vaccine, they were trying to stimulate antibodies against
mouse eggs, which would make the animals infertile. The
mousepox virus was merely a vehicle for transporting the egg
proteins into mice to trigger an antibody response. The
researchers added the gene for IL-4 to boost antibody
production. The surprise was that it totally suppressed the
"cell-mediated response"--the arm of the immune system that
combats viral infection.
Mousepox normally causes only mild symptoms in the type of
mice used in the study, but with the IL-4 gene added it wiped
out all the animals in nine days. "It would be safe to assume
that if some idiot did put human IL-4 into human smallpox
they'd increase the lethality quite dramatically," says Jackson.
"Seeing the consequences of what happened in the mice, I
wouldn't be the one who'd want to do the experiment."
To make matters worse, the engineered virus also appears
unnaturally resistant to attempts to vaccinate the mice. A
vaccine that would normally protect mouse strains that are
susceptible to the virus only worked in half the mice exposed
to the killer version. "It's surprising how very, very bad the
virus is," says Ann Hill, a vaccine researcher from Oregon
Health Sciences University in Portland. If bioterrorists created
a human version of the virus, vaccination programmes would
be of limited use.
Alibek, who now works on developing novel treatments for anthrax
for the defence contractor Hadron in Virginia, says this highlights
the drawback of working on vaccines against bioweapons
rather than treatments. "I'd say any vaccine could be overcome
by one or another genetically engineered virus or bacterium," he says.
Is it possible that research into new vaccines against cancer
and other diseases could inadvertently create lethal human
viruses? Many of the most promising modern vaccines depend
on viruses to transport genes into the body, and contain
genes that directly alter the immune response. But researchers
have not been too concerned because the evidence until now
suggested that changes in the genetic make-up of viruses
invariably makes them less virulent, not more. One way to
reduce the risk, says Gary Nabel of the National Institutes of
Health, is to use only viruses that cannot replicate. "There are
some replication-competent [viral vaccines] around, but there
is increasing concern about their use," he says.
Defence experts are also worried about preserving the freedom
to publish medical findings while trying to stop the information
falling into the wrong hands. According to D. A. Henderson, a
former US presidential adviser, and director of the Center for
Civilian Biodefense Studies at Johns Hopkins University in
Baltimore, what are effectively blueprints for making
microorganisms more harmful regularly appear in unclassified
journals. "I can't for the life of me figure out how we are going
to deal with this," he says.
The Australian researchers consulted their country's
Department of Defence before submitting the work for
publication, and only decided to go ahead after considerable
thought. A report will appear in a February issue of the Journal
of Virology. "We wanted to warn the general population that
this potentially dangerous technology is available," says
Jackson. "We wanted to make it clear to the scientific
community that they should be careful, that it is not too
difficult to create severe organisms."