October 16, 2011
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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.
About the Author: Lucas Brouwers is fascinated by evolution. He writes about science on his blog and for a Dutch daily newspaper. Follow on Twitter @lucasbrouwers.
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Seems like an important point buried in your footnote, that the medieval bacterium could have had entire sequence(s) that the modern one doesn’t. Yet the researchers are talking like they feel confident it has hardly changed, how come?
Link to thisThanks for your comment Vasha!
The inability to find sequences that are absent in modern samples is indeed an important limitation of targeted enrichment. Since it’s impossible to say anything about DNA that medieval Yersinia might or might not have had, the researchers could only investigate the genetics to point mutations in known sequences, where they find few differences between old and new strains.
If Yersinia really did lose genes/plasmids over time , I doubt if we will ever be able to a) find them and/or b) assign them to Yersinia with confidence (since ancient DNA is so fragmented).
Link to thisHi, I’d like you to send me a copy of “the Rise and fall of nano bacteria” as it relates to a piece I’m working on. Scientific American is an oxymoron. Its nether American or Scientific, more like a readers digest version of sciency stuff.
If you were a Californian (we are not American ether according to some trolls) you would be told by an old-timer like me that them nasty little ground squirrels (GS) in the Sierra Nevada (SN) die in a camp ground every so often get sent to the Lab (probably UCDavis) and yep, got the bubonic plague (BP) and shut down the camp ground then send out press release that every body ignores.
I’ve always wondered if during the 1849 gold rush a nasty rat jumped ship, squirried up to the SN met up with some GS transferring a few friendly fleas and wa lah, we got BP. —OR— (here it comes) its been there forever (like before humans showed up). So it would be interesting to find out if Our SN BP had a genome similar to the other ones still hanging out around on this rock.
Ummm… messing with the order of alleles ? Sounds like a great way to massively mutate and destroy a cell line pretty fast (just a thought). This is not in the context
of horizontal gene transfer and contagens but I doubt they gave that obvious observation any thought. If they had the anticipation of the reaction to their paper would have been anything but boring.
There is more little nuggets for ya, that article was an IED (improvised explosive device) I got a nuke. The way it goes critical (like any good war head) is by horizontal gene transfer in the wild == bio-weapon.
Real science is weird, how many mutations does it take for a cell to become immortal ? I’m not sure but it sure kills a lot of people.
Thanks beforehand for the article. I’ve got a bunch of papers on the subject I’ll fact check and share with you, but this lethality thing can get pretty intense.
GOOD VALIDATION: PMID: 21993626
“Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype.”
FLAWED: PMID: 21876176
“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.” ——Lucas Brouwers
GOOD JOB, WE AGREE.
Link to thisHi Lucas, thanks for a great post, really enjoyed reading it.
Someone made the same point re the ‘extinct’ storyline at the Science Online Conference in London last month. I’m not sure if it was you?
PNAS sends out a weekly forecast of what’s going to appear in the journal for journalists. This includes short briefs of the papers to be published.The extinct storyline came from the brief for this paper.
Might be worth letting the authors know and contacting the PNAS news team.
Link to this@Gozde – Wait, the PNAS paper says in the abstract “Our data reveal that the Black Death in medieval Europe
was caused by a variant of Y. pestis that may no longer exist”.
I’m not entirely sure what the criticism is here. Is it that the press jumped on the story? I don’t buy that at all. Poinar says “They never expected that it would have interested anyone outside the field”. Really? Even without the full genome, they dug up plague victims and started sequencing Black Death DNA! That’s cool!
If it’s that the two mutations turned out to be wrong, well, that’s science, isn’t it? What does the media do – hold back on reporting in case things turn out to be wrong?
If it’s the claims about the Black Death being “extinct”, well, the fact that the strain was close to the ancestor of modern plagues doesn’t invalidate the conclusion that it’s no longer around. It doesn’t have derived mutations compared to modern strains, but equally, there’s no modern strains that’s quite like it.
Disclaimer: I wrote about both papers, and I had the word “extinct” in my headline about the first one.
Link to thisHi Ed, I’m talking about the brief that the PNAS news team send out to journalists, not the abstract from the paper.
Link to thisI didn’t cover this story, haven’t even looked at the paper. Just wanted to Lucas to know that the ‘extinct’ storyline featured strongly in the briefing sent out by the PNAS news team because he couldn’t find anything in the paper to suggest otherwise.
Link to thisThanks for your comments Gozde and Ed!
@Gozde: I hadn’t looked at the PNAS briefs. That might explain why the ‘extinct angle’ featured so prominently in the media coverage, while it was only a minute component of the original research.
@Ed: My main criticism is that the ‘story’ of the medieval strain becoming extinct won out over the nature of the research itself. The study was not set up to investigate the evolutionary fate of the Black Death strain, something that the authors made clear in their discussion. This is not mentioned in any of the coverage that I have read.
I have no problems with two mutations being wrong. That, as you say, is science (that the authors disprove their own results in such a short span of time is unusual, of course).
Regarding your last point, being extinct really is something else than ‘not being around’. The Black Death is like a deceased grandaunt (not the most flattering of comparisons, I know). There’s nobody quite like her alive today, but relatives of her are (whether they are direct descendants or not). I think we all agree that it’s silly to declare this grandaunt as ‘extinct’.
Link to thiswho.int/csr/resources/publications/plague/whocdscsredc992a.pdf
Look at p.12
[...] “studies have shown that disruption of key components in the competence regulon inhibits DNA transformation and attenuates virulence. Thus, synthetic analogues that competitively inhibit CSPs may serve as attractive drugs to control pneumococcal infection and to reduce horizontal gene transfer during infection.”
Link to thisExcellent post!!!! I could not agree more. My personal suspicion is that reporters who covered the first paper did not actually READ it…but then, that would not be a first.
Link to this