KEY TO STRAINS OF ANTHRAX IS DISCOVERED
27 Mar 2003
Source: New York Times, March 27, 2003
Key to Strains of Anthrax Is Discovered
By WILLIAM J. BROAD
Scientists have discovered why different strains of the bacterium that causes anthrax differ so much in virulence, a finding that in theory could produce more effective vaccines and better tools for distinguishing and tracking the lethal germ.
But the finding could also aid the creation of designer varieties of anthrax that are potentially deadlier to humans. Because of that potential danger, a debate occurred over whether the discovery should be kept secret, scientists said. In the end, it was decided that the benefits of publication outweighed the risks.
The discovery was made by six scientists at Louisiana State University, the Lawrence Livermore National Laboratory and the United States Army Medical Research Institute of Infectious Diseases, the nation's top center for studying germ defenses. It is published in the current Journal of Clinical Microbiology.
The lead author, Dr. Pamala R. Coker, formerly at L.S.U. and now at the Livermore laboratory in California, spearheaded the research for her Ph.D. dissertation. The Livermore laboratory once pioneered nuclear arms but increasingly studies biology and germ defenses.
The team's finding centers on the anthrax genome, which consists of a single large chromosome and two small circles of DNA, known as plasmids, that carry extra genes. The scientists found that, contrary to common belief, each anthrax bacterium carries not just one set of plasmids but up to 243 copies of the first and up to 32 copies of the second, which is known as pX02. The more copies of this plasmid in a bacterial strain, the more it is capable of causing disease, the scientists said.
The research was conducted in guinea pigs. The scientists found, for example, that an anthrax strain from Mozambique that possessed just one pX02 plasmid killed 25 percent of the test animals. But a strain from Australia with 32 copies of the plasmid left all the guinea pigs dead.
The team of scientists also reported that added factors like subtle features of the bacterium's DNA chromosome appeared to help determine virulence. Thus, the anthrax that killed five Americans in the germ attacks of 2001 — the so-called Ames strain — was found to possess just two copies of pX02. But it nonetheless killed 62 percent of the guinea pigs.
The pX02 plasmid carries genes that let the anthrax bacterium fashion an outer protein coat that acts as a defensive shield to thwart the immune system of hosts. The scientists suspect that multiple copies of pX02 thicken that coating, letting the germ escape immune damage and multiply to do extensive harm.
Scientists had previously identified 89 types of anthrax as genetically distinct but had failed to discover what determined their wide differences in virulence. The plasmid findings, they said, opened a new window on that question.
"It's very interesting," said Dr. Sam Kaplan, a microbiologist at the University of Texas medical school at Houston. "But a lot more work needs to be done."
Dr. Martin E. Hugh-Jones, a team member at L.S.U., said the discovery would help scientists understand why some anthrax vaccines are effective and others weak. "This will allow us to do some very impressive things in coming on with new vaccines," Dr. Hugh-Jones added.
It could also aid investigations of germ attacks. Dr. Coker of the Livermore laboratory said the finding could help forensic scientists track down the country and laboratory from which the weapon arose. That, she said, was possible because the plasmid technique acted as a kind of microscope to reveal finer genetic distinctions among the 89 known varieties of anthrax. A match between the attack germ and a library of detailed fingerprints could help locate the perpetrator.
Dr. Coker conceded that the research in theory could also help a genetic engineer make a more deadly form of anthrax by increasing the number of pX02 plasmids.
Dr. Kaplan of the University of Texas, who heads the publication board of the American Society for Microbiology in Washington, said no reviewer or official of the society raised objections to publication of the plasmid paper, even though the White House has urged scientists to screen their work carefully for possible harm to national security.
Steve Wampler, a spokesman at the California laboratory, said the plasmid research was done before Dr. Coker came to Livermore but the laboratory nonetheless put the paper through a careful security review. "In the end," he said, "it was decided that it was fine to publish."
In addition to Dr. Coker of Livermore and Dr. Hugh-Jones of L.S.U., the paper's authors are Dr. Kimothy L. Smith of the Livermore laboratory, Patricia F. Fellows of the Army research institute, and Dr. Galena Rybachuck and Dr. Konstantin G. Kousoulas of L.S.U.