Scientists Map Genome of the Plague

But will knowing its blueprint thwart bioterrorists?

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By
HealthDay Reporter

WEDNESDAY, Oct. 3, 2001 (HealthDayNews) -- Scientists say they've mapped the genetic sequence of the organism responsible for the waves of bubonic plague that killed 200 million people during three pandemics in the last 2,000 years.

Knowing the genetic makeup of the bacterium Yersinia pestis could help researchers develop antibiotics, vaccines or other defenses against the plague, experts say. A report on the findings appears in the Oct. 4 issue of Nature.

Plague is considered one of the likelier bioterror weapons, and with good reason: It has been used before. In the low-tech 14th century, Mongol invaders sparked a massive European outbreak of the disease by catapulting pestilent corpses over the city wall of Caffa, a trading town in the Crimea.

In May 2000, Colorado conducted a simulation in which mock terrorists sprayed an aerosol containing microbes into a Denver performing arts center. Within three days, officials say the spray would have caused 3,700 cases and 950 deaths, with patients cropping up in seven states.

The Black Death, or bubonic plague -- so called for the swollen lymph nodes, or buboes, it causes -- is transmitted to humans through contact with rodent fleas, such as those that feed on infected rats. Human-to-human transmission occurs through droplets of blood coughed or sneezed by an infected person.

Plague comes in three forms: bubonic, when it afflicts the lymph nodes; septicemic, when it enters the bloodstream, and pneumonic, when the bacteria colonize the lungs. Each is potentially curable with antibiotics if caught early, but the blood and lung variety are rapid killers that require more immediate treatment. The trouble, say experts, is that plague can kill a patient within 48 hours or so, and by the time it's diagnosed it's often well on its way.

The last significant eruption of plague in the United States occurred in Los Angeles in the 1920s. It has since been confined almost exclusive to rural regions, and accounts for only about 10 to 15 cases nationwide a year, says the Centers for Disease Control and Prevention (CDC). Worldwide, plague infects 1,000 to 3,000 people annually.

In the sequencing effort, Julian Parkhill of the Sanger Center in Cambridge, England, and his colleagues analyzed the genome of a Y. pestis bacterium isolated from a patient who died of pneumonic plague.

The organism consists of a single chromosome, with 4.65 million base pairs of DNA building blocks, attended by three much smaller doughnuts of DNA known as plasmids. The chromosome includes 21 stretches of genes that appear to be implicated in both infecting humans and fleas.

But for all its lethality, Parkhill says the rod-shaped germ is architecturally banal. "There's nothing in the genome you can point your finger at" to explain its extraordinary killing powers, Parkhill says. The combination of its ability to survive in rats and people, its free passage between the two hosts, its relative transparency to the human immune system and other factors "are responsible in part for its virulence," he says.

The organism appears to have evolved from Yersinia pseudotuberculosis (not a relative of tuberculosis) thousands of years ago. In the process, it accumulated new genes and deactivated others on its way to becoming so dangerous.

A map of the plague's genome has been available in chunks on the Internet for several years. Parkhill says the completed sequence enables "a fundamental acceleration of any research into" ways to combat plague. "Every possible drug target, every possible vaccine target is in there," he says.

Even so, John Pape, an epidemiologist and resident plague expert at the Colorado Department of Public Health and Environment in Denver, says the information is of little immediate use to disease officials charged with handling an outbreak. "We know how it works, what the [epidemiology] is," says Pape.

More important, he says, is educating doctors and hospitals about the signs of plague so that they're alert to a possible attack. A decade ago, when bioterrorism was just an academic threat, even modest safeguards didn't exist. "Clearly we're in a lot better shape than we were. Clearly there's a lot more work to be done," he says.

Pape considers plague a "top-five" candidate disease for bioterrorists. It's relatively easy to find and grow, and its extremely deadly. On the other hand, he says delivering it becomes problematic for all but the most advanced attackers. "That's where Joe in the garage would quickly run out of expertise," says Pape.

What To Do

For more information about plague, try the CDC or the Virtual Museum of Bacteria.

For more on defending against bioterrorism, visit the Center for Civilian Biodefense Studies at Johns Hopkins University.

SOURCES: Interviews with Julian Parkhill, Ph.D., project manager, Sanger Center, Cambridge, England, and John Pape, epidemiologist, Colorado Department of Public Health and Environment, Denver; Oct. 4, 2001, Nature; Centers for Disease Control and Prevention photo

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