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Reconstructing Black Death: Why Was Plague Microbe so Deadly?

October 13, 2011 at 12:00 AM EST
Researchers announced Wednesday that they've managed to reconstruct the genome of the Black Death, the illness that wiped out around half of Europe's population in just a few years in the mid-1300s. Ray Suarez discusses the developments with geneticist Hendrick Poinar of McMaster University.
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JUDY WOODRUFF: To a story with origins many centuries ago.

Scientists have recently unraveled the genetic code of the black plague and are studying its relevance for our modern age.

Ray Suarez has the story.

RAY SUAREZ: The microbe that caused the Black Death killed some 30 million people in Western Europe in the mid-14th century. Researchers have long tried to understand how the bacterium really could have been that deadly.

Now scientists have collected DNA from the bones of Black Death victims buried in a London cemetery. The genetic blueprint was taken from extracted teeth and then compared with modern-day bubonic plague.

Geneticist Hendrik Poinar of McMaster University in Canada was a leading member of the team. And he joins me now.

Professor, welcome.

Why sequence the genome of a bacterium that was killing people almost 700 years ago?

HENDRIK POINAR, McMaster University: I think one of the reasons is really so that we can hope to understand perhaps why it was so deadly. So were there intrinsic changes in the genome of the Black Death pathogen that led to be exceptionally virulent, leading to this high mortality, which you just mentioned killed some 50 percent of the European population in 1346.

RAY SUAREZ: So you managed to track down a sequenceable piece of bacterium. What did it tell you once you were able to compare it with the plague bacterium of today?

HENDRIK POINAR: Yes.

Well, first, we had to design this methodology to actually remove, like you mentioned, just really small, tiny fragments, because the pathogen had been heavily degraded into little tiny, bitty pieces.

And so what we had to do is actually manage to pull that out using sort of an enrichment strategy and then stitch these pieces back together to actually construct this ancient genome. And then using that, we can compare it to the modern genomes, which allow us then to deduce, A., that this turns out to be sort of the grandmother of all modern circulating plague, pestis bacteria today out across the globe. So outbreaks in Southwestern United States or outbreaks across Africa and India actually have a root that sits within medieval Europe in the 14th century.

RAY SUAREZ: There’s been very little change in the bacterium, from what I understand. How come it was so much more deadly then than it is today?

HENDRIK POINAR: That’s an excellent question, Ray, the million-dollar question, I would say.

We don’t quite know yet. We do have a constellation of changes in this bug which we need to test to find out. So was it an intrinsic structure within the bug, so the actual way the genes are organized on that chromosome that actually led to increased virulence? Or, actually, if we step back a bit, was it actually immune susceptibility in populations at that time?

And if we step back even further and we look at the context of medieval Europe at that time period, the climate was much colder than it was the years previous to 1346. Rains began and never seemed to end. And I’m sure, as people entered this cold phase of the year, it was really co-circulating pathogens, people with flus and other immunocompromised individuals, and then when the arrival of this new pathogen into mainstream Europe through trade routes sort of led to a perfect storm of sorts.

RAY SUAREZ: Let’s go back to the skeletons recovered in a London mass grave. Were you pretty confident that you could extract something usable from 660-year-old corpses?

HENDRIK POINAR: Well, we were never able to in the past really get large amounts of sequence information from the pathogens, so — let alone finding the DNA of humans in human skeletal remains is already a big enough challenge with ancient DNA.

But to find the proverbial needle in the haystack, which is the pathogen embedded within the actual complete extract, is an even more difficult challenge. It’s sort of not a needle in a haystack. It’s more like needle in the University of Michigan football stadium.

And so we had to devise a novel methodology that actually uses modern ancient plague bacterial DNA spotted on to a glass slide to actually pull those DNA fragments out of this complex mixture of DNA solution from these skeletonized remains. So it’s the development of this novel technology which then enabled us, with high-throughput sequencing, to actually restitch this genome back together.

RAY SUAREZ: Were you thinking about that as you were pulling teeth out of a centuries-old corpse, or were you saying, what am I doing? This better work.

(LAUGHTER)

HENDRIK POINAR: Yes. Yes.

Well, we had no idea at the onset, when we began this project in the mid-’90s, as to whether or not this would ever be done. In fact, if you had asked me two years ago whether or not we could actually reconstruct the first ancient pathogen genome from skeletons, I would have probably said probably very unlikely.

So — but here we are today. And we have managed to do it. And I think this gives us sort of a time machine to travel back to access the genomes of past plagues across our human history, to be able to address what changes actually allowed these pathogens to adapt to their human hosts and ultimately why they became so deadly.

RAY SUAREZ: So, you have climbed up to this plateau. What does it allow you to do? Could you actually reformulate a 14th century version of Yersinia pestis, and would it be dangerous to do it?

HENDRIK POINAR: You could, actually.

Well, that’s a good question. First of all, you could. And I think there’s good reason to do that. So the question that you asked just earlier is, why was it so deadly? We have no idea, really. And it’s very hard to imagine going into a densely populated city today and imagining, oh, every third person dropping from an infectious disease rampaging through the city.

And so really understanding what it was that made this so deadly is a key part of this research at this point, and that involves actually taking some of the genes and trying to reconstitute them and looking for changes in sort of the enzymatics of what it does. So that can be done.

The good news is, if we look at the entire sequence and we compare it against known sequences of pathogens that are susceptible to antibiotics, we see that modern tetracyclines that we use in antibiotic studies today would be quite effective against this plague of the Middle Ages.

So had medieval Europe had access to tetracyclines, they probably would have fared much better.

RAY SUAREZ: Professor Hendrik Poinar, thanks for joining us.

HENDRIK POINAR: Thanks for having me, Ray.