Scientists in St. Louis have created a genetically altered strain of mousepox virus -- a close relative of the smallpox virus -- that is so potent it kills mice vaccinated against the mouse disease, rekindling concerns that some avenues of biotechnology research may be generating lethal knowledge useful to bioterrorists.
Health officials emphasized that the federally financed work posed no threat to people. Although the mousepox virus is highly contagious and lethal in mice, it does not cause illness in humans.
But given the similarities between the mousepox and smallpox viruses, scientists said, the same technique might be useful for making a beefed-up strain of smallpox virus that could kill people despite their having been vaccinated.
The lead researcher, virologist Mark Buller of Saint Louis University, said he has already heard from many people distressed about his work, details of which he presented at a scientific meeting in Geneva recently. "I've received all this hate mail," he said.
He added, however, that others have done much the same thing in other labs. The big difference, Buller said, is that his effort was aimed not just at making bad viruses but also at finding a treatment that would work against them. And happily, he reported, he was successful.
The research and its reverberations in recent days highlight an ongoing debate in the scientific community, the federal government and the public about the relative risks and benefits of microbiological research that might be adapted for bioterrorism purposes.
Since the anthrax attacks of 2001, the government has looked for ways to curb the dissemination of new and dangerous knowledge about disease-causing organisms. At the same time, experts have argued, the best way to prepare for a possible bioterrorism attack is to allow research to proceed as unimpeded as possible.
Earlier this month, the National Research Council, an independent congressionally chartered advisory group, recommended steering clear of major research restrictions and instead creating a new level of federal review for proposed experiments that pose particular biosecurity risks -- including any research that aims to make microbes more virulent or resistant to vaccines. That system is not in place yet, though federal officials say they are working quickly to implement it. If it were, scientists agreed, Buller's research clearly would have triggered an extra review.
What Buller did was insert an extra gene into the mousepox virus -- a gene that can suppress the immune system of the mouse that the virus is infecting, thus making it easier for the virus to overcome that animal's defenses.
This was not the first time such work had been done. Indeed, it was the accomplishment of just such a feat by Australian researchers in 2001 -- by accident, it turned out, while they were trying to design a mouse contraceptive -- that first drew many experts' attention to the possibility that scientists might naively help terrorists as they went about their everyday work.
Concerns about that and a few similarly worrisome studies have already prompted editors of scientific journals to create a self-imposed review system in which potentially dangerous details may now be occasionally censored. Those concerns also helped prompt the NRC to produce its report.
Buller said yesterday that he has "absolutely no biosafety issues" with his work. The mousepox virus does not infect humans, the gene involved is specific to mice, and the work had been done by others before.
"The things we did to make that virus more virulent is kindergarten stuff," he said.
Although he acknowledged that someone could, in theory, apply similar techniques to smallpox, he said he had no qualms about presenting his data at the Geneva meeting because his team had found two different ways of countering the enhanced virulence with drugs and vaccines, and is close to perfecting a third way.
The meeting, "Smallpox Biosecurity: Preventing the Unthinkable," took place Oct. 21 and 22 and was sponsored by a biotechnology company that is making a new version of the smallpox vaccine.
Lawrence Kerr, assistant director for homeland security in the White House Office of Science and Technology Policy, praised the work.
"This is the type of research we view as critically important to this nation's biodefense research-and-development portfolio," Kerr said. Buller "was developing countermeasures to a model of a very dangerous pathogen and doing everything in a completely safe mouse model," he said.
Kerr applauded the new level of biosecurity awareness that he said biologists have shown in the past year or so and offered reassurance that the government has no intention of placing heavy-handed restrictions on research or the publication of results.
Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, the part of the National Institutes of Health that funded the work, said that even under the current system of grant review Buller would have had to clear extra hurdles if he wanted to use his techniques in viruses that can infect humans.
"If he wanted to go beyond this . . . he'd have to get further permission from us," Fauci said.
"For goodness' sake," Fauci said. "We already know how to do this. Everybody knows how to do this. The hard part is figuring out how to counter it."