Australian scientists have accidentally created a virus that kills mice by crippling their immune systems, and warn that the technique may threaten to produce deadlier forms of human viruses and new kinds of biological weapons.

The scientists were trying to make the mice infertile, but unintentionally created a killer.

They added a gene involved in the mouse immune system to the mousepox virus, which is a cousin of the human smallpox virus that is widely used in lab studies.

Mice infected with the pathogen died, even many of those who had been vaccinated against mousepox.

Because people have the same immune system gene, in theory a similar step could create a pathogen deadly to people.

Previously, scientists exploring the shadowy world of designer pathogens found that superbugs made by genetic engineering often turned out to be less potent than their natural progenitors. It seemed that virulence was easier to lose than enhance.

So the Australian scientists, from the Australian National University in Canberra, say the discovery of how easy it is to make such a viral killer should ring global alarm bells. They called on all nations to strengthen a global treaty that seeks to ban germ warfare.

The surprise discovery was made over a period beginning in 1998 and ending in 1999. At first, the scientists informed only the Australian government and military about it. But after some debate, "We thought it was better that the information came out in case somebody constructed something more sinister," said Ronald J. Jackson, the lead researcher for the team.

American researchers noted, though, that similar pathogens created in the past have remained laboratory curiosities that produced no known weapons or harm. In interviews, they said that while the Australian discovery was ominous, much remained unknown about whether the technique could be applied to human viruses and, if so, whether new classes of designer pathogens would become available.

The scientists made the discovery while exploring ways to help protect global food supplies from mice and rats. The scientists were trying to use mousepox virus to create an artificial strain of the microbe that would render mice infertile.

Instead, they found that inserting a particular mouse gene made the virus deadly for breeds of laboratory mice normally resistant to the disease. They also found that vaccines against mousepox became far less effective.

In this case, they found that certain changes to a mouse virus can render it more lethal and harder to immunize against.

An American biologist who works for the Defense Department on germ defenses said "It demonstrates a frightening message," he said. "Maybe it's easier to do these things than we think."

The best protection against any misuse of this technique was to issue a worldwide warning.

The mousepox virus has no affinity for people and poses no threat to humans.

But the scientists worry that unethical biologists might adopt the method to strengthen weapons based on human viruses, possibly turning even the common cold into a killer.

Annabelle Duncan, head of molecular science at the Commonwealth Scientific and Industrial Research Organization, the nation's main science agency, said the discovery suggested that "we need urgently to strengthen" the Biological Weapons Convention, a 1972 treaty that bans germ warfare.

For years, states have negotiated unsuccessfully to make the treaty more rigorous. Their efforts have been thwarted mainly by disputes over how to police modern biology and medicine.

After gene splicing was invented in 1973, a quiet debate arose in military and scientific circles over whether designer pathogens would really be more harmful than what nature produced, or whether added genes might backfire and leave them weaker. Evidence on both sides has often been murky, partly because the work is sometimes done in secret.

The Journal of Virology is published in Washington by the American Society for Microbiology, the world's top group of germ scientists.

The Australian scientists inserted into the mousepox virus a mouse gene that controls the making of interleukin-4, chemical that plays a starring role in the immune system's responses to foreign invaders. The aim was to enhance the making of interleukin-4 and thus the immune response so that even mice eggs would be rejected as foreign, blocking mouse reproduction.

But the female mice instead died, as did many of those vaccinated to resist mousepox. The scientists say the designer virus unexpectedly crippled the immune system to such an extent that the microbe reproduced wildly, killing most of the mice and making the rest permanently disabled.

The mousepox virus, they added, was used simply because it was well studied and convenient. If successful, the experiment would have progressed to inserting the interleukin-4 gene into a benign microbe of rodents, the murine cytomegalo virus.

The bodies of people, like those of mice, use interleukin-4 to control immune responses. Its signals are one of the main ways biological reactions to infection are orchestrated. That similarity is one reason the new finding worries experts.

New York Times January 23, 2001

Journal of Virology February 2001