For anthrax sleuths, 60 steps forward

Scientists unveil genetic 'markers' that could help resolve questions about the sources of anthrax attacks.

When envelopes carrying anthrax spores appeared in Florida and Washington last fall, investigators quickly shipped samples to a lab in northern Arizona to see if researchers could tease from the organisms' genes clues that would help point to the attacks' source.

While no arrests have been made, that effort has made important progress: the discovery of the most detailed set of genetic tags yet for anthrax. The discovery raises hopes that detectives in the future will be able to effectively trace the sources of anthrax or other bioterrorism agents.

The research, published online yesterday by the journal Science, comes at a time of increasing frustration among law enforcement agencies trying to solve last fall's anthrax attacks, in which five people were killed. By some estimates, the attack cost the economy several billion dollars.

A team of scientists working at two US labs sequenced the genomes of different varieties of anthrax, including one mailed to a Florida newspaper last fall, then comparing them to look for slight variations. The approach uncovered at least 60 new genetic "markers" that the scientists say can help distinguish between strains of Bacillus anthracis.

Until now, scientists had perhaps a dozen coarser genetic indicators they could use. These markers helped trace the anthrax isolate from Florida to samples taken from a dead cow in Texas in 1981. Those samples wound up in at least 14 labs via the US Army's Medical Research Institute of Infectious Disease at Fort Dietrich, Md.

But these coarser markers don't show scientists the subtle genetic mutations that can occur naturally as generations of isolates grow in the lab. Hence they couldn't identify which of the labs the isolate might have come from.

While scientists can predict which regions of the genome "will mutate more quickly than others, knowing which of these will be different among close relatives is still the problem," says Paul Keim, a microbiologist at Northern Arizona University in Flagstaff, one of two labs participating in the study. "Whole-genome sequencing can identify very rare mutational events that provide discriminating power."

The extent to which genome sequencing will help the current investigation is unclear.

Barbara Rosenberg, director of the Federation of American Scientists' Chemical and Biological Arms Control Program, says its promise is for the long term, not solving last fall's attacks.

But some experts say it could help winnow down the list of labs from which the attacks could have originated.

Efforts to "cross examine" and compare variations among more strains have the potential to "lead to the identification of the source of the 2001 bioterrorism strains," notes Craig Cummings of the Stanford University School of Medicine.

The Institute for Genomics Research in Rockville, Md., has been funded to sequence at least 10 more strains. TIGR is the second lab involved in the results reported yesterday.

Researchers note that several steps must be taken before the approach is ready for widespread use. One is to reduce the cost. Sequencing a single strain can set a lab back $140,000. Dr. Keim reportedly has 1,200 strains in his lab alone.

In addition, each strain must be sequenced enough times to ensure that researchers have a handle on the range of mutations that can occur within it.

A gene-sequence library also needs to include the many anthrax microbes found in nature, so scientists can distinguish between a planned attack and a natural outbreak.

Apart from their potential as biological bloodhounds, anthrax genomes also could pave the way for better antibiotics to combat infection, public-health experts say.

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