These plague victims were excavated from the East Smithfield burial grounds between 1986 and 1988.

The plague bacteria that swept through medieval Europe had been declared extinct just over a month ago. A quick google search reveals articles with headlines such as 'Medieval plague bacteria strain probably extinct' and 'Black death strain extinct'. Few writers mentioned that the original research on which they reported was a technical paper first and foremost, and not a comprehensive investigation into the evolution of the Medieval plague.

It's ironic that a study that was published last week shows that the Black Death is far from extinct. On the contrary. The plague bacteria that still infect thousands of people every year trace back their ancestry to the plagues of the fourteenth century. Interestingly, this new research was carried out by the same scientists that published the other plague study in August, so what has happened here?

In their first paper, researchers lead by Johannes Krause and Hendrik Poinar announced that they had successfully extracted and sequenced some DNA of a medieval strain of Yersinia pestis, the bacterium that causes plague, from the teeth of a dozen Black Death victims. These remains had been excavated from the East Smithfield burial grounds in London by the Museum of London Archaeology before. During the height of the London plague epidemic, between 1348 and 1349, thousands of bodies were buried at East Smithfield.

Since DNA degrades over time, the researchers used modern Yersinia DNA as bait to fish out the fragmented medieval sequences ( a technique called 'targeted enrichment'). The team found enough ancient DNA in this way to reconstruct a plasmid, a small ring of DNA, that belonged to medieval Yersinia. The paper is full of calibrations, controls and corrections that the researchers applied to make sure that their DNA wasn't contaminated or damaged.

John Norden's map of Londen (1593), with the East Smithfield cemetery coloured red

So where did the conclusion that the medieval strains of Yersinia pestis are extinct come from? There is only one result in the entire paper that hints at this possibility: "[the medieval sequences] revealed the presence of two mutations that, to our knowledge, are not found in any Y. pestis sequences, either ancient or modern." While these two mutations make an interesting observation, they do not provide enough evidence to justify some of the grand, sweeping claims about the Black Death’s demise that were made in the media. The researchers specifically mentioned that an investigation of the plague’s evolutionary history fell outside of the scope of this research.

I wrote a story about this disconnect between the media coverage and the research itself in NRC Handelsblad, the Dutch daily newspaper that I write for. The lead researcher of that paper, Hendrik Poinar, then told me that he was 'flabbergasted' with all the media attention that this study had received. The team hadn’t even prepared a press release about their work. They never expected that it would have interested anyone outside the field. Poinar later wrote me in an e-mail that "the PNAS paper was not the 'landmark study' people were making it out to be."

At the time, Poinar was also careful to point that their findings didn’t prove the Black Death was extinct. "Only when we have the complete [medieval] genome, can we begin to reconstruct the evolutionary history of the plague", is what he told me back then.

Little did I know that this medieval genome was almost ready to be published. Now, one and a half months later, the genome is there. Krause and Poinar reconstructed the entire DNA sequence of medieval Yersina pestis, with the same technique of targeted enrichment that they had used earlier. They found over two million pieces of medieval DNA and stitched these back together into a single genome. This is quite an achievement. It is the first time that scientists have managed to reconstruct the complete genome of an ancient, disease-causing bacterium. Even more exciting is that this genome reveals a story that directly contradicts the articles that were making the rounds on websites and newspapers earlier. The medieval Black Death isn’t extinct. Its descendants still cause disease today and have barely changed for over 660 years.

The Black Death appears to have been much more deadly in medieval times, but when the researchers compared the genomes of the medieval and modern Yersinia side by side, they hardly found any differences between them *. If the medieval Yersinia really was more dangerous than its modern counterparts, there's no trace of its increased lethality in the bug's DNA. Even the genes that are known to be important for causing death and disease have remained the same for over 650 years.

“For a long time we thought the bug was the culprit”, says Poinar, “but now we suspect that the interplay between the disease and humans was what made the medieval plagues so devastating. Fourteenth century London was a crowded, cold and damp. Large parts of the population were malnourished and many were carrying other diseases, such as the flu. Then suddenly the plague arrives with the merchant ships from Southern Europe. It was a perfect storm.”

Poinar and Krause believe that the plague grew less severe over time because the people of Europe adapted. This was a biological adaptation in part, since only the people able to muster some resistance to the deadly disease survived. But there was also cultural adaptation. Starting in the sixteenth century, many cities in the Netherlands constructed 'plague houses'’for example, where bearers of the plague were quarantined and treated by specialized plague doctors. Nasty outbreaks still struck Europe every now and then, such as the Great Plague of London in 1665, but never again were they so deadly as in 1348.

Plague doctors wore beak-like masks to protect them from 'bad air'.

Another unexpected find was that all modern plagues seem to trace back their ancestry to plagues from medieval times. This raises some questions about another major pandemic in human history, the Justinian plagues that swept through the Byzantine empire in the sixth century. These plagues were always believed to be the same disease as the one that devastated medieval Europe. If this is so, these Justinian Yersinia strains have left no descendants that have survived into modern times. Another possibility is that the Plague of Justinian was a different disease altogether. “What caused the Justinian Plague has really become the next million dollar question”, Poinar says.

What about the two unique mutations that the team had found in August? They turned out to be an artifact. The 'mutations' turned out to be a form of DNA damage that is typical for ancient samples. When the researchers resequenced the same positions using next generation sequencing technologies that cover the same position multiple times, they found no trace of the 'mutations'. The Black Death had been proclaimed dead to soon.


*: Poinar points out that there might be genetic variations between medieval and modern Yersinia that they have missed with their approach. While they did reconstruct the entire Yersinia genome, it was not possible to determine the exact order of its genes. Yersinia pestis is known for rapidly shuffling its genes around, but it is not known how this gene order could affect its deadliness and capacity to cause disease. Also, because the team fished for medieval DNA using modern sequences as bait, it is impossible to find the sequences that were lost or gained between the ancient and modern strains.


Images:

Plague victims from East Smithfield: Museum of London Archaeology

John Norden's map of London made available by Mike Calder

Doktor Schnabel von Rom ("Doctor Beak of Rome"), engraving by Paul Fürst (1656)

References:

Schuenemann VJ, Bos K, Dewitte S, Schmedes S, Jamieson J, Mittnik A, Forrest S, Coombes BK, Wood JW, Earn DJ, White W, Krause J, & Poinar HN (2011). Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death. Proceedings of the National Academy of Sciences of the United States of America, 108 (38) PMID: 21876176

Bos KI, Schuenemann VJ, Golding GB, Burbano HA, Waglechner N, Coombes BK, McPhee JB, Dewitte SN, Meyer M, Schmedes S, Wood J, Earn DJ, Herring DA, Bauer P, Poinar HN, & Krause J (2011). A draft genome of Yersinia pestis from victims of the Black Death. Nature PMID: 21993626