Scientists Solve Puzzle of Black Death’s DNA
After the Black Death reached London in 1348, about 2,400 people were buried in East Smithfield, near the Tower of London, in a cemetery that had been prepared for the plague’s arrival. From the teeth of four of those victims, researchers have now reconstructed the full DNA of a microbe that within five years felled one-third to one-half of the population of Western Europe.
The bacterium that causes plague, Yersinia pestis, is still highly virulent today but has different symptoms, leading some historians to doubt that it was the agent of the Black Death.
Those doubts were laid to rest last year by detection of the bacterium’s DNA in plague victims from mass graves across Europe. With the full genome now in hand, the researchers hope to recreate the microbe itself so as to understand what made the Black Death outbreak so deadly.
So far, the evidence points more toward the conditions of the time than to properties of the bacterium itself. The genome recovered from the East Smithfield victims is remarkably similar to that of the present-day bacterium, says the research team, led by Kirsten I. Bos of McMaster University in Ontario and Johannes Krause of the University of Tübingen in Germany.
This is the first time the genome of an ancient pathogen has been reconstructed, opening the way to tracking other ancient epidemics and how their microbes adapted to human hosts.
The bacterium’s genome consists of a single chromosome, about 4.6 million DNA units long, and three small rings of DNA called plasmids. In the 660 years since the Black Death struck, only 97 of these DNA units have changed and only a dozen of these changes occur in genes and therefore would affect the organism’s physical properties, the researchers report in Wednesday’s issue of the journal Nature. Dr. Krause and others reported the DNA sequence of one of the plasmids in August. The changes in the genome will be studied one by one to see how each affects the microbe’s virulence.
The researchers hope eventually to modify a living plague bacterium so that its genome is identical to that of the agent of the Black Death. Such a microbe could be handled only in special secure facilities. But even if it did infect a person, the bacterium would be susceptible to antibiotics, like its living descendants, said Hendrik Poinar of McMaster University, a team member.
If the microbe’s genome is so little changed, the deadliness of the Black Death may reflect the condition of its medieval victims. Harsh as the economic stresses assailing Europe today may be, they are a breeze compared with problems in the mid-14th century. The climate was cooling, heavy rains rotted out crops and caused frequent famines, and the Hundred Years’ War began in 1337. People were probably already suffering from malnutrition and other diseases when the plague arrived like the fourth horseman of the apocalypse. “People honestly thought it was the end of the world,” Ms. Bos said.
Recovery of the medieval plague bacterium’s full genome is a technical tour de force. The DNA had been degraded into millions of small fragments that were overwhelmed in number by DNA from the human host and from the bacteria that consumed the body after death. Dr. Krause’s team fished out the plague DNA by using DNA from the modern bacterium, relying on the fact that DNA strands bind to DNA of complementary sequence.
“This is a major technological step forward, a great advance for the entire field of DNA and pathogens,” said Mark Achtman, an expert on ancient plague at University College Cork in Ireland.
But Dr. Achtman disagreed with one issue in Dr. Krause’s findings, that of whether Yersinia pestis also caused the outbreak in the sixth century known as the Justinian plague. When the full genome of the medieval bacterium is compared with DNA recovered from other known human outbreaks, a tree of descent can be constructed. The Black Death genome lies so close to the root of the tree that the human pathogen probably did not exist much earlier or, if it did, has vanished without any descendants, Dr. Krause’s team says. This implies that the Justinian plague was caused by some other agent.
Dr. Achtman said this conclusion was incorrect because the Krause team had omitted DNA from several human cases that place the root of the tree much further back in time. Dr. Krause said he had left these cases out because they seemed unreliable.
The modern plague bacterium changes its DNA units slowly, but it does quite often rearrange the order of its genes. Some experts believe gene order can affect pathogenicity. Dr. Krause had available only tiny fragments of DNA, so although he was able to reconstruct all the medieval bacterium’s genes he could not establish the exact order in which the genes were arranged, leaving open the possibility that the bacterium was inherently more pathogenic because its genome was differently organized.
Paul Keim, an expert on infectious bacteria at Northern Arizona University, said that work by Dr. Achtman and Dr. Krause had shown that the Black Death “was really a series of epidemics coming out of China and sweeping across the susceptible ecological situation” created by the culture of medieval Europe. The plague in each outbreak probably did not persist very long and was repeatedly re-established by new infections from East Asia, where the bacterium is still endemic in small rodents like marmots.
“We don’t have a human ecological situation comparable today, plus it is really easy to break the transmission cycle with antibiotics and public health,” Dr. Keim said. There are still small outbreaks, like one in Madagascar in the 1990s, but “a multiyear large human outbreak is inconceivable in this day,” he said.
Besides the Justinian plague and the Black Death, a third great wave of plague swept out of China in 1894, causing an epidemic in San Francisco in 1900 and killing millions of people in India.
All the teeth used in the study will be returned to the skulls from which they were taken, now in a London museum whose archaeologists excavated the East Smithfield cemetery in the 1980s.
From The New York Times Science Section