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An Empire's Epidemic

Scientists Use DNA in Search for Answers to 6th Century Plague


By the middle of the 6th century, the Emperor Justinian had spread his Byzantine Empire around the rim of the Mediterranean and throughout Europe, laying the groundwork for what he hoped would be a long-lived dynasty.

His dreams were shattered when disease-bearing mice from lower Egypt reached the harbor town of Pelusium in AD 540. From there, the devastating disease spread to Alexandria and, by ship, to Constantinople, Justinian's capital, before surging throughout his empire.

By the time Justinian's plague had run its course in AD 590, it had killed as many as 100 million people--half the population of Europe--brought trade to a near halt, destroyed an empire and, perhaps, brought on the Dark Ages. Some historians think that the carnage may also have sounded the death knell for slavery as the high demand for labor freed serfs from their chains.

Justinian's plague was a "major cataclysm," says historian Lester K. Little, director of the American Academy in Rome, "but the amount of research that has been done by historians is really minimal."

Los Angeles Times Saturday May 11, 2002 Home Edition Main News Part A Page 2 A2 Desk 1 inches; 22 words Type of Material: Correction
Plague bacterium: An article on Monday's Science page about the bacterium that causes plague incorrectly included a reference to the pathogen as a virus.

Little is hoping to do something about that. In December, he brought the world's plague experts together in Rome to lay the groundwork for an ambitious research program on the pandemic. A book resulting from the meeting will be published this year.

Modern techniques for studying DNA have begun answering long-standing questions about the evolution of the plague bacillus, how it infects humans and what can be done to counteract it.

While a 6th century plague might seem an esoteric subject, Little and others think that it has great relevance in a modern world that is continually threatened by emerging diseases. A second pandemic of plague struck Europe in the Middle Ages--the so-called Black Death--killing 25 million people and once more producing widespread social disruption.

A third pandemic began in China in the late 19th century and spread to North America, where a large reservoir of the disease remains active in animals throughout the Southwest.

An outbreak occurred in Los Angeles in 1924-25, but was contained.

Plague could become a tool of bioterrorists. Russian experts have long argued that plague is a much more frightening prospect than anthrax. As part of their germ war efforts during the Cold War, Soviet scientists developed strains of plague resistant to antibiotics used to cure infections. Unleashing such organisms could potentially have a devastating effect on modern society.

Understanding Justinian's plague could also lead to insights into other types of disasters, man-made and natural, adds UCLA historian Michael Morony.

"People were dying faster than they could be buried," he said. "I find myself wondering how society survived. That's a relevant question to try to understand."

Plague is caused by a bacillus called Yersinia pestis, identified in 1894 by the Swiss bacteriologist Alexandre Yersin. The bacterium once killed more than half the people it infected but is now routinely controlled by such antibiotics as streptomycin, gentamicin or tetracycline.

Plague Still Kills

2,000 People a Year

About 2,000 deaths from plague are still reported worldwide every year, a handful of them in the United States. Naturally occurring strains resistant to antibiotics have been observed recently, however, and scientists fear that their spread could lead to large outbreaks.

Y. pestis is carried by rats and other animals. It can be transmitted to humans by direct exposure to an infected animal. Most often, however, it is carried by fleas that bite the infected animals, then bite humans.

People bitten by such fleas develop agonizingly painful, egg-sized swellings of the lymph nodes--called buboes--in the neck, armpit and groin. Hence the name bubonic plague.

Some authorities recognize two other forms of plague, one called pulmonary or pneumonic, in which the lungs are affected, and one called septicemic, in which the organism invades the bloodstream, but all are the same disease, Little said.

Because of its possible use in bioterrorism, researchers have been actively studying the plague organism. In October, a British team from the Sanger Center in Cambridge reported that they had decoded the complete DNA sequence of Y. pestis, a feat that could help to control outbreaks.

"The genome sequence we have produced contains every possible drug or vaccine target for the organism," said Dr. Julian Parkhill, the team's leader.

Genetics shows that the closest relative of Y. pestis is a gut bacterium called Yersinia pseudotuberculosis, which is transmitted through food and water and which causes diarrhea, gastroenteritis and other intestinal problems, but is rarely fatal. Y. pseudotuberculosis may be the immediate ancestor of Y. pestis, but it is not transmitted by fleas. Last month, researchers apparently discovered why.

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