10/12/2011 01:43 EDT | Updated 12/12/2011 05:12 EST

Black Death Genetic Code Cracked In Work Led By Canadian Scientists


TORONTO - A team of Canadian, German and American scientists has cracked the genetic code of the bacteria that is believed to have caused the Black Death.

The work opens the door to the possibility that science can now chart the centuries-long evolution of a bacteria that was one of the worst killers of all time, but now is relegated to pockets of activity in the developing world. The scientists said modern strains of the bacteria are all descendants of the Black Death variant.

An estimated 50 million people died during the Black Death's five-year reign of terror in Europe in the mid-14th century. Today the bacteria believed to have caused that outbreak — Yersinia pestis or plague — claims about 2,000 lives a year in parts of Africa, India and China.

The full sequence of the ancient Yersinia bacteria was put together from fragments of DNA recovered from human teeth found in a mass grave for Black Death victims in east London, near the site of the Tower of London.

The project was led by Hendrik Poinar, director of the Ancient DNA Centre at McMaster University in Hamilton, and Johannes Krause of the University of Tubingen in Germany. The report on their work was published Wednesday in the journal Nature.

It was hailed as an impressive piece of science.

"It's very cool," said Dr. Jeffery Taubenberger, the American scientist who led the effort to find and sequence the virus responsible for the 1918 Spanish flu pandemic, the only previous time a pathogen of old has been decoded.

To have gone from tiny fragments of DNA to the completed genome is "an extraordinary technical advance," said Taubenberger, who runs a lab at the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Md.

This group of scientists reported in late summer that they had found small fragments of the Yersinia DNA. That represented 0.002 per cent of the genome, Krause said, whereas now 99 per cent of the bacteria's genetic code has been sequenced.

Poinar credited rapid technological advances for making the work possible.

"Even up to a year ago it was basically a pipe dream to get this level of genomic information," he said in a telephone interview.

There has been a long-standing debate in scientific circles as to what caused the Black Death of 1347 to 1351, with most bets riding on the plague. But some scientists argued that a viral hemorrhagic fever was more likely to blame, pointing to the fact that contemporary plague does not kill with the speed and spread of the Black Death.

"It's been sort of plaguing — no pun intended — people for many, many years as to the epidemiological patterns being different than modern day plagues," explained Poinar, who said this work puts a lot more weight behind the plague theory.

Poinar's team is still working with the material collected from the teeth to see if they can identify other disease agents that might have infected the victims at the time of death.

He and his colleagues speculate the Black Death cut such a deadly swath because it may have been the first time the pathogen moved through the human population, meaning no one had antibodies to protect against it.

As well, conditions at the time were perfect for the spread of diseases. Homes and communities were crowded, there was no sanitation, people were malnourished and, as antibiotics and antiviral drugs had not yet been discovered, infections could not be treated.

"That goes back to this whole notion that that was 1348 — wet, foggy, mushy London where people were co-infected probably with a million other bugs," Poinar said. "We have fantastic labs and we have antibiotics."

Poinar noted that an expert in antibiotics has studied the genome and believes the drugs used to treat current day plague cases would be effective against the 14th century variety.

While Poinar and Krause argue their findings help make the case that the Black Death was plague, they suggest the work throws doubt on the claim that an earlier outbreak, the Justinian Plague of the 6th century, was also caused by plague.

Analysis of the genome of plague viruses suggests it started to infect humans for the first time somewhere between 1200 and 1340, Krause said.

The DNA was recovered from teeth from four different jaws found in the East Smithfield pit, a mass grave dug in late 1348 or early 1349 to inter the bodies of people who died from the Black Death.

Two of the individuals were adult females and one was a juvenile whose gender cannot be determined. The scientists cannot estimate the gender or age of the fourth person.

The researchers were able to extract DNA fragments from the pulp of the teeth. Using modern day genetic sequences of Yersinia pestis bacteria as a template, they were able to put together the 14th century version of the plague.

The differences between the current day bacteria and the resurrected bacteria are not enormous; it's not immediately apparent what made the earlier version a mass murderer. Poinar notes, though, that they are not certain what the correct order of the genes is. Figuring that out may help explain why the ancient bacteria was so virulent.

As well, there are small differences in the bacteria that may provide clues, he said. "We don't find necessarily a smoking gun. (But) there are a handful of substitutions which are quite interesting which are worth following up on."

His group is collaborating with scientists in New York to try to home in on the significance of those genetic changes.

Working in high biosecurity laboratories, those scientists are looking to see whether changing the code of modern day Yersinia strains to include those substitutions would ramp up the virulence of the bacteria. They are doing the work in chemical assays, not animals.

As required by the rules of scientific publishing, Poinar's team will put the sequence for the ancient Yersinia bacteria into Genbank, an open access database.

He acknowledges that will likely cause alarm in some quarters.

"I think it makes some people nervous," he said. "(But) science has to move forward and we need to know if these are indeed changes and could these changes account for the increased virulence and can we control for that virulence today."