British scientists have deciphered the genetic blueprint of bubonic plague, the fearsome microbe that killed one-third of medieval Europe and could still be a frightening biological weapon in the hands of modern-day terrorists.
The new gene map could offer clues to vaccines and other drugs that could keep the disease in check and perhaps even neutralize its use as a weapon.
Antibiotics have all but eliminated plague as a naturally recurring killer. Worldwide, only about 2,000 cases are reported annually, including a dozen or so in the American Southwest.
But scientists warn that plague probably is triggered by a particularly crafty bacterium, Yersinia pestis. Already, it has mutated into at least one drug-resistant version since 1997.
The gene map for Y. pestis is published in Thursday's issue of the journal Nature.
"The genome sequence we have produced contains every possible drug or vaccine target for the organism," said the leader of the research team, Julian Parkhill of the Sanger Center in Cambridge, England.
Plague was known as the Black Death in the Middle Ages because symptoms included liquefying of the organs and hemorrhaging, which caused dark splotches under the skin.
The microbe can be transmitted to humans by fleas that have fed on the blood of an infected rat. It also is spread in airborne droplets when infected people cough. Both forms can be treated with antibiotics, but the airborne version develops so rapidly that it is almost always fatal within a few days.
"These properties make Y. pestis one of the most feared agents of biological warfare or bioterrorism," said microbiologist Stewart Cole of the Pasteur Institute in Paris. "The information provided by the genome sequence should be applied to ensure that plague does not re-emerge, and that one of the potential weapons of bioterrorism can be neutralized."
Normally, a gene map for an all-but-vanquished disease would interest only microbiologists and medical historians. But fears of biological warfare have increased since the Sept. 11 terrorist attacks. The U.S. government grounded crop-dusting airplanes for several days after the attacks. Spreading plague bacteria in the air could mimic the effects of the inhaled version of the disease.
Biological agents can be unstable and have been difficult to "weaponize." During the Cold War, U.S. and Soviet laboratories assigned thousands of researchers to put plague and other biological agents in aerosol form.
Stocks of Y. pestis are kept in several microbe banks around the world. In 1997, an Ohio man pleaded guilty to illegally obtaining plague germs from a Maryland commercial laboratory.
Like most genetic discoveries, the new plague gene map is widely available to scientists. Officials said it would not be helpful to terrorists.
"The problems that they would need to overcome, such as large-scale growth and dispersal, would not be assisted by the sort of molecular information we have produced," Parkhill said.
The gene map shows that Y. pestis adapts quickly and adroitly. As civilization concentrated in crowded, dirty cities, Y. pestis became hardier and more infectious. It changed from a gut-dwelling microbe to a blood-borne source of disease, using fleas to leap from rats to humans. Y. pestis continues to remodel itself quickly, Parkhill said.
At least three major plague outbreaks claimed 200 million lives in the past 1,500 years.
In 541 A.D., the first outbreak swept through the Roman Empire. Europe's Black Death started in 1347, killing 25 million in Europe and 13 million in the Middle East and China within five years.
The third major outbreak started in China in 1894. By 1900, it had spread worldwide, killing 12.5 million in India alone. A large outbreak was contained in Los Angeles in 1924-25.