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

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.pestis. Other teams did their own analyses, and things went back and forth with a panto-like tempo. Oh yes, Y.pestis was there. Oh no it wasn’t. Oh 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

17 thoughts on “The lost plague – London graveyards suggest that Black Death strain may be extinct

  1. @ Kasem: Slim to none, that would be like dinosaurs coming back to life (An exaggeration, but same idea). DNA breaks down pretty easily once an organism dies. The sequences separate, pieces get lost and the fragments become useless. Other bacteria could theoretically absorb the broken fragments of DNA, but that’s pretty unlikely, and much less likely to result in anything worth worrying about.

  2. Thanks for telling this story the way it really unfolded, without hyperbole. The stories I’ve seen about it leave out salient adjectives or toss in modifiers that belie the facts, making it sound, for example, as though Yersinia pestis of any kind is now extinct, etc.

  3. I’m a bit surprised by the amount of attention that this study has received. This is a technical piece of work first and foremost. The real achievement is that the scientists managed to completely reconstruct an ancient plasmid is, but this is hardly talked about in most press coverage (I’m glad you mention it Ed).

    The “Black death is extinct”-angle is based on two synonymous mutations that were found on the Yersinia chromosome, indicating that this medieval killer was a strain of its own. This is hardly surprising, and not something new either. Other unique strains of Yersinia pestis have previously been identified on the basis of SNPs, with more interesting conclusions tied to them (a dual introduction of plague bacteria): http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001134

    “Furthermore, on the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route.”

  4. @1 Kasem,

    I too used to worry about these ancient killers reappearing. However there is a key fact rarely mentioned when this topic comes up.

    The Black Death was a feature of the 1300’s, long before the germ theory of disease, antiseptics, vaccines and so forth. It disappeared as mysteriously (to the poor citizens of medieval Europe) as it appeared. Most of the efforts of people at the time were ineffective, with a partial exception for shunning and isolation.

    Now we are much better equipped to deal with such diseases. Even better, the public health lessons have been learned. For the majority of the population, they do not live in conditions that are hospitable to plague. The role of fleas and rats as plague vectors is understood so we target those both directly and indirectly.

    Summing up, even if the bubonic plague were to reappear in it’s ancient, lethal form, it would have a terrible time trying to gain a foothold in the population. We know it too well and have numerous effective interventions.

    Fun fact: did you know that certain small mammals in North America carry plague? And sometimes they manage to infect people too. It’s rare and quite treatable.

  5. Sorry I’m so late to the party, but I was wondering if the strain of Y pestis that they found could be linked to specific features of plague infection? I know that traditional plague the way we think of it is spread by flea bites, but there are also strains of plague which kill much faster and are spread in the air (via coughing, etc). This was called “pneumatic” plague and is thought to be much faster spreading and far deadlier than the kind spread in what we usually think of as the traditional manner. Do we now think that the plague from the 13th century was maybe pneumatic, or had pneumatic features (usually I think pneumatic didn’t have the buboes associated with bubonic plague), rather than being strictly bubonic? I don’t know a lot about this, just wanted to ask.

  6. Could it be that the lower fatality rate today is a result of the fact that the ancesters of those of us living now were the offspring of those people who were exposed to the plague and survived it?

  7. Another great, fascinating article. I passed it on to a friend who is teaching a European history course this semester and was covering the black plague last week. She enjoyed it enough to consider using it as a source in future semesters, although she did raise a point about the numbers of people killed by the Black Plague. I thought I would share her response:

    “…Thank you so much for passing on this article to me. I am constantly amazed at how our knowledge of the past is in such a state of flux; history, as I constantly remind my students, is truly a never-ending argument.

    I do wonder, however, at the claim at the start of the article which asserts that the Black Death killed approximately 100 million people. At the height of the High Middle Ages, the population of Europe was only around 75-100 million, and it had certainly fallen by the time of the Black Death’s first onslaught in 1349 due to wasting famine in the early decades of the 14th century. I generally stick to the consensus historical view that approximately 20 million died in the first 3-year outbreak. Perhaps the writers meant that upwards of 100 million people have died over the centuries due to the plague?”

    So I am wondering about the 100 million death figure (or to be fair, what you refer to as up to 100 million); did it refer to the Black Plague specifically, or a larger cumulative figure?

    By the way, I have used a variety of your posts as a resource in classes over the years, and have shared them with colleagues in Biology. I thought you might find it gratifying that psychologists, biologists, and now historians in one location are engaged in conversations connected to your work.

  8. A friend of mine from Arizona caught the plague. The local doctors figured out what she had quickly and cured her. She wasn’t especially impressed by the disease, which she told me was no worse than a bad case of the flu; but it’s true she had been treated promptly with antibiotics.

  9. @Scicurious: just a tiny but significant correction: it’s “pneumonic…” not “pneumatic…” plague (although I admit your error made me smile)! The latter refers to air-operated machines! The former to airborne and lung-infecting forms of diseases, such as plague and anthrax…and is, indeed, related to the word root of “pneumonia”.

  10. Also…(sorry to have omitted this in my earlier post)…I don’t think that pneumonic plague is necessarily a different “strain” of the bacterium than that causing the other forms of the disease, but, like the parallel with anthrax, a different phase of the “natural history” of the disease as it affects an individual, which may or may not arise in the course of a particular individual’s infection. When it does, of course, its route of transmission increases its virulence substantially. Perhaps someone more familiar with plague etiology can enlighten us on this point. Thanks.

  11. I also enjoyed reading The Plague a few years ago – devastating emotionally – Ben – loved your correction – made me smile too! I could have easily made the same error! I know the Hanta virus is also active in the US…

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