The lost plague – London graveyards suggest that Black Death strain may be extinct

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The road of East Smithfield runs through east London and carries a deep legacy of death. Two cemeteries, established in the area in the 14th century, contain hundreds of bodies, piled five deep. These remains belong to people killed by the Black Death, an epidemic that claimed up to 100 million lives. It was one of the biggest disasters in human history and seven centuries on, its victims are still telling its story.

In the latest chapter, Verena Schuenemann from the University of Tubingen and Kirsten Bos from McMaster University have reconstructed parts of the genome of the Black Death plague bacterium, and found features that are unlike any seen today. In line with another study from last year, Schuenemann and Bos’s work suggests that the great butcher of medieval Europe may no longer exist.

Of course, plague is still around, caused by a bacterium called Yersinia pestis. The Black Death is generally assumed to be an intense pandemic of the same disease. It’s the second of a trilogy that began with the Plague of Justinian in AD 541 and that continues with modern plague, which infects some 2,000 people a year. But some scientists and historians saw features in the Black Death that separates it from other plague pandemics – it spread too quickly, killed too often, recurred too slowly, appeared in different seasons, caused symptoms in different parts of the body, and so on.

These differences have fuelled many alternative theories for the Black Death, which push Y.pestis out of the picture. Was it caused by an Ebola-like virus? An outbreak of anthrax? Some as-yet-unidentified infection that has since gone extinct? In 2000, Didier Raoult tried to solve the debate by sequencing DNA from the teeth of three Black Death victims, exhumed from a French grave. He found Y.pestis DNA. “We believe that we can end the controversy,” he wrote. “Medieval Black Death was plague.”

Raoult was half-wrong. The controversy did not end. Some people argued that it’s not clear if the remains came from Black Death victims at all. Meanwhile, Alan Cooper analysed teeth from 66 skeletons taken from so-called “plague pits”, including the one in East Smithfield. He found no trace of Y.pestisHe found no trace of Y.pestis. Other teams did their own analyses, and things went back and forth with a panto-like tempo. Oh yes, Y.pestis was thereOh yes, Y.pestis was thereOh yes, Y.pestis was there. Oh no it wasn’t. Oh yes it wasOh yes it was.

Schuenemann and Bos’s study is the latest volley. It not only confirms the idea that the Black Death was plague, but it might explain why that particular pandemic was so different to the others – it was Y.pestis, but not as we know it.

They extracted DNA taken from 99 bones and teeth, previously exhumed from East Smithfield, and found Y.pestis in 20 of them. They’re sure that the sequences haven’t come from modern contaminants. Aside from the usual precautions, they also did all of her work at a facility that had never touched a Y.pestis sample, they had the results independently confirmed in a different lab, and they found traces of DNA damage that are characteristic of ancient sequences. They also failed to find any Y.pestis DNA in samples treated in exactly the same way, taken from a medieval cemetery that preceded the Black Death. Finally, it’s clear that the people exhumed from East Smithfield did indeed die from the Black Death – it’s one of the few places around the world that has been “definitively and uniquely” linked to that pandemic.

Many of the Y.pestis sequences came from a plasmid – a ring of DNA that sits apart from the bacterium’s main genome. This one, known as pPCP1, is responsible for many of the features that set Y.pestis apart from its close relatives and contains many of the genes that allow it to grow in human hosts, and spread to new ones. However, pPCP1 wasn’t responsible for the unique nature of the Black Death – the Smithfield sequences were no different to those of modern strains.

However, Schuenemann and Bos also sequenced fragments of the bacterium’s main genome, and these contained two mutations that aren’t found in any known Y.pestis sequences, modern or ancient. This alone suggests that these sequences couldn’t have come from modern bacteria.

It’s unlikely that these two mutations were specifically responsible for the unusual nature of the medieval plague pandemic. After all, neither of them would have led to any changes in the bacterium’s proteins. However, they do suggest that the ancient strain was something different to those we study today, and perhaps one that is no longer around.

“There is really no way to know anything about the biology of the pathogen, until the entire genome is sequenced,” says Hendrik Poinar, who led the study. Doing that is difficult because the bacterium’s DNA has been so heavily fragmented over time. However, his team is on the case. Perhaps the victims of this lost plague will eventually tell us about the genetic changes that made it such a potent killer.

That knowledge could be very important. Plague has a habit of rebounding through the centuries and the World Health Organisation classifies is as a “re-emerging” disease. “We need to know what changes in the ancient one might have accounted for its tremendous virulence,” says Poinar. “Than perhaps we can be better prepared should it ever re-emerge in its past form.”

Reference: Schuenemann, Bos, deWitte, Schmedes, Jamieson, Mittnik, Forrest, Coombes, Wood, Earn, White, Krause & Poinar. 2011. Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death. PNAS http://dx.doi.org/10.1073/pnas.1105107108