Now an international team of researchers, including Canadian disease detectives, have determined the two pandemics resulted from distinct strains of the bacterium that causes plague.
Using tiny fragments of DNA extracted from the 1,500-year-old teeth of two Justinian plague victims buried in Germany, the scientists were able to reconstruct the genome of the strain of Yersinia pestis that caused the AD 541-543 pandemic — making it the oldest pathogen genome decoded to date.
While the Justinian strain flared up periodically over the next hundred years to cause subsequent outbreaks, it eventually died out, said Hendrik Poinar, an evolutionary geneticist who directs the Ancient DNA Centre at McMaster University.
The strain that caused the Black Death, ravaging half the population of Europe eight centuries later, was a distinct form, which re-emerged in the late 1800s and spread worldwide, he said.
"The Justinian looks like it came, it flared up, it killed its people and then there were no more suitable hosts or it didn't survive underground and did not re-emerge in that form," Poinar said. "So the Black Death is actually a completely novel emergence of Yersinia pestis 800 years later."
The findings, published Monday in the journal Lancet Infectious Diseases, suggest a new strain of plague could emerge again in humans in the future.
"We know the bacterium Y. pestis has jumped from rodents into humans throughout history and rodent reservoirs of plague still exist today in many parts of the world," said Dave Wagner of the Center for Microbial Genetics and Genomics at Northern Arizona University, one of the study's co-authors.
"If the Justinian plague could erupt in the human population, cause a massive pandemic and then die out, it suggests it could happen again," Wagner said in a release. "Fortunately, we now have antibiotics that could be used to effectively treat plague, which lessens the chances of another large-scale human pandemic."
The DNA samples used in the research were taken from two victims of the Plague of Justinian —named after the Roman emperor of the time — who were buried in gravesites in an early medieval cemetery in Aschheim, Germany, near Munich.
Based on carbon-dating and grave goods found with the skeletal remains, scientists believe the victims died in the latter stages of the epidemic when it had reached southern Bavaria, sometime between 541 and 543.
German scientists first identified possible Yersinia pestis in some of the buried victims, then passed their findings to experts at the University of Arizona for comparison to modern-day plague strains. Those groups then contacted Poinar's lab, which specializes in ancient DNA and had reconstructed the genome of the Black Death strain in 2011.
"We are the ones that took the teeth, extracted the DNA and basically pulled the little fragments out," said Poinar, adding that over time, the breakdown of matter in burial pits produces an intermingled "soup" of DNA from humans, plants, insects, bacteria and fungus.
"And deep, deep, deep, buried in that mess, were these tiny fragments of Yersinia," he said. "Basically what we do is we design very sensitive, selective 'fishing rods' that can pick out Yersinia like tuna or maybe more like Chilean sea bass from the Pacific waters, something that's infrequent."
Poinar's lab determined that the strain responsible for the Justinian outbreak was an evolutionary "dead-end" and distinct from strains involved later in the Black Death and other plague pandemics that would follow.
The third pandemic, which spread from Hong Kong around the world in the 1800s, is likely a descendant of the Black Death strain and thus much more successful than the one responsible for the Justinian plague.
"We really have built this time machine to go back into deep time and really look at co-infections and host-pathogen evolution, and I think that's critical to understanding infectious disease dynamics," said Poinar. "Without understanding, you can't really predict epidemics or prepare for them."
While relatively rare, cases of plague still occur today in certain areas of the world, including the western United States, transmitted to humans from rodents infected with the bacteria, typically by fleas.
In 2012, Oregon welder Paul Gaylord was bitten by his cat, which had been infected by a plague-carrying mouse. He survived after being on life-support for a month, but later had to have all of his blackened and withered fingers and toes amputated.
"I think this is a good reminder that plague is an ever-present bug," said Poinar. "As climate changes and these rodents move because their ecology changes, because of food or aridity or whatever it might be, they come into contact with rodents that are susceptible to plague and you can have a new epidemic that begins.
"So being consciously aware of where Yersinia pestis is, which particular strains are present in a rodent population at a certain point in time and how those rodents are moving according to climate change is critical for understanding or being prepared for a possible re-emergence down the road."
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