DNA Detective Work Identifies Black Death Culprit
IRA FLATOW, host: For the rest of the hour, a case study of how genetics is revolutionizing what we know about human history - and in this instance that I'm talking about, the history of the Black Death, the bubonic plague. Modern plague is caused by the bacterium Yersinia pestis - Yersinia pestis. But for decades, scientists and historians have debated whether the medieval plague was indeed caused by this same bug, or was it something else? Maybe it was anthrax or a virus. Well, a study out this week in the Proceedings of the National Academy of Sciences answers some of those arguments.
One of my next guests is an author on that paper. And he reports finding DNA evidence of the same bacteria responsible for the plague today, in the skeletons of English victims of the Black Plague. But the DNA isn't the whole story. For example, are there still some mysteries around - like what made the plague so virulent and quick to spread in the 14th century? Was it just a slightly different strain of the bug that we see today? Well, some - these are some great questions, we're going to try to answer them now with my guests. Hendrik Poinar is an evolutionary geneticist at McMaster University in Hamilton, Canada. Welcome to SCIENCE FRIDAY, Dr. Poinar.
Dr. HENDRIK POINAR: Well, thanks for having me, Ira.
FLATOW: You're welcome. Michael McCormick is chair of the Science of the Human Past program at Harvard. He's also the Goelet professor of medieval history there. Welcome to SCIENCE FRIDAY, Dr. McCormick.
Dr. MICHAEL MCCORMICK: Thank you very much. It's great to be here.
FLATOW: You're welcome. You know, we were all taught about the Black Death as kids. You know, it was carried by rats. They had fleas and whatever, and they infected people. Is that not the truth?
MCCORMICK: Well, there's been a lot of informed debate about that subject. Right from the outbreak of the third pandemic of plague that's going on right now; in the late 1890s in China, scientists began to identify it with the medieval Black Death. But as knowledge deepened and as scholars went more carefully through the evidence, a number of factors emerged that caused them to be - caused some of them to be more or less skeptical. And threw the identification open for debate.
They argued - some argued for a while that rats aren't mentioned in medieval texts at the right time. Others argue that rats weren't found in the archeological evidence, and plague is first and foremost a disease of rats. And we get it from rodents and particularly from the black rat. And so there were - then there were anomalies that it seemed to appear in the medieval descriptions of some of the symptoms. And so there was a lot of healthy debate about this.
FLATOW: Did you say that there's a plague going on now in China?
MCCORMICK: There's a plague going on now in the United States. This has become - the third pandemic plague began in the late 19th century, reached San Francisco in the 1890s, around 1900. And it's been moving steadily westward transmitted by squirrels and prairie rats.
FLATOW: No kidding.
MCCORMICK: Oh, yes. The Southwestern United States has a very good public health warning system for plague. We have a few cases every year.
FLATOW: Yeah. Hendrik, tell us what you've done here with the DNA.
POINAR: Well, that's - our interest has really been to try and identify sort of larger genetic sections of the DNA from Yersinia pestis embedded in the skeletal remains. And so, this has always been a sort of complex thing because, of course, a skeleton buried in a plague pit that's over 600 years old is, of course, a heavy mixture of the DNAs of bacteria and fungi and the insect, and any rodent that may have dug through the pit at that time. And so in addition to the endogenous human DNA that you'll have, you have a tremendous amount sort of contaminating exogenous DNA. And so we've always been interested in trying to find this needle in the proverbial haystack of DNA sitting there in these skeletal remains.
FLATOW: And you did find it?
POINAR: And we did. Yeah, we did. Of course, people have argued that there are other close circulating pathogens, so that's something, of course, that we would like to continue to look at with these - the advent of these high throughput sequences now on the market. It's actually a much easier thing to do. But, yeah, so we had to really develop a novel method to actually target these few - very few - sort of circulating stretches of tiny DNA of the pathogen actually still preserved within the root cavity of the teeth that were still embedded in the jaws that we actually removed from the, the jaws from the skeletal remains at the British Museum.
FLATOW: All right. We're going to talk more about tracking down the origins of the plague and identifying it today, with Hendrik Poinar and Michael McCormick. Stay with us. We'll be right back after this break.
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FLATOW: You're listening to SCIENCE FRIDAY. I'm Ira Flatow. We're talking about the history of the plague and tracking down DNA evidence for it to prove that it might be similar to the kind of plague that's still around today. Talking with Hendrik Poinar from McMaster University in Hamilton, Canada; Michael McCormick of Harvard. Our number, 1-800-989-8255. If you'd like to - and we were talking about, gee, this was a really interesting - with Hendrik about - you've dug out DNA from the teeth of people buried in the 14th century.
POINAR: That's right. Yeah.
FLATOW: Where was this?
POINAR: These were skeletal remains actually excavated in the late 18 - 1980s by the British Museum in a pit called the East Smithfield gravesite. And this was actually purchased - we have historical documentation showing the land actually purchased by the king for an additional mass gravesite because the numbers were filling up in the other gravesites too quickly. So he needed additional land to build a pit to bury additional people. I'm sure, Michael, you know much more about this than I do...
FLATOW: Michael, chime in if you'd like.
MCCORMICK: ...was a wonderful excavation. The Museum of London did a great job of doing the excavation and then preserving the remains and organizing. In fact, they put, as Hendrik knows well, they've put them all up on an online database to allow scientists and scholars to have access to the visual...
POINAR: Actually, they've done an absolutely fantastic job there. And so we were...
MCCORMICK: Yep. It's fantastic.
POINAR: ...yeah - allowed to actually go in. And we thought, well, we'll test the skeletal remains, the actual bones and - but then, we thought probably it'd be much better thing to target the teeth, because if we can actually get - actually still any remaining blood within the root cavity of the teeth, we might have a much better chance of actually catching the pathogen within there, because any biochemist or anybody who studies bones knows that, despite the fact that they look quite good coming out of remains, they're actually quite porous.
They're like a sponge. And so they always absorb everything, which means that they're highly susceptible to hydrolytic damage, which, of course, is any kind of water. And for molecular structures such as DNA, the last thing you want is moving water back and forth. So these teeth were actually fantastically well preserved. And my graduate student, Kirsti Bos, actually removed the teeth from the skulls, drilled into the actual root cavity, up into the pulp, removed the pulp, and then put the teeth back into the jaws and then reset the jaws in the skull. So that way, we wouldn't actually affect the morphology of the remains.
FLATOW: Well, where there any danger that your graduate student could have gotten sick from the plague by drilling into the teeth?
POINAR: That's right. Well, that's why I sent my graduate student...
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FLATOW: That's why I emphasized that.
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MCCORMICK: I think it's important to note that it...
POINAR: Well, (unintelligible)...
MCCORMICK: ...(unintelligible) it's denatured. It's broken down.
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POINAR: That's right. We assumed it had to be degraded.
MCCORMICK: (Unintelligible) in large part comes with dealing - which the new technology permits, dealing with these tiny, tiny base pairs. I think the size of the genome of Yersinia pestis bacterium is about two million. Is that right, Hendrik?
POINAR: Well, the chromosome is about four and a half million...
POINAR: ...and then, there's these extracellular plasmas that are - they range from 10 to about 100,000 base pairs in length.
MCCORMICK: And you were working with base - set sequences of 40 or 50 base pairs.
POINAR: That's right. That's right. We literally had 30 to 40 base pairs stretches, which is tiny, tiny, tiny.
FLATOW: Well, then, how can you make that and come to your conclusion with such - with DNA in such bad shape - that it is the same Black Plague that we have today?
POINAR: Well, that involves the new technology that we, sort of, described and the methodology we described in the paper is we're able to actually - so what you can do is you can actually - we can take the sequences on the available databases for the modern pestis strains. And we can artificially create what we like to call or what we describe to our students in the lab like a type of fishing line that actually has a set of complementary DNA pieces on this fishing line that, of course, match perfectly the modern Yersinia pestis - one of the Yersinia pestis strain.
And then what we do is we actually float that fishing line into this massive pooled extract of everything I've told you about. So the actual pathogen is there at very, very low frequency and then all the additional bacteria, human DNA, everything else that you don't want to catch. And under the right conditions, which are temperature and salt conditions, you can actually get your DNA of your pathogen to actually bind to this fishing line. That fishing line is actually, itself, attached to proteins which can then attach to magnetic beads which then we can use a magnet to pull that fishing line back out, thereby enriching only for the pathogen DNA and not for all the rest of the co-circulating fragments that are polluting your extract.
FLATOW: Michael, how did the Black Death spread so fast? The...
MCCORMICK: That's a remarkable story, too. So it actually got started from one of the earliest cases of biological warfare when the Mongols were besieging an Italian colony on the Black Sea in modern-day Ukraine, and they were not getting anywhere and the plague broke out in their camp. So they catapulted bodies with - of cadavers of those who died from the plague into the Italian fortress, the Genoese, and it broke out there. And it sailed back to Europe; it affected not only the Genoese but the rats in the colony. And they boarded the ships and with the ships of the Genoese and then the Venetian traders, which were binding together this pulsating European economy as the European economy was reaching towards its peak - its medieval peak in the 14th century. They carried the disease with them to every port they went to.
Now, we can track the outbreaks as they're reported in archival records, and you really get an X-ray of the shipping schedules of the great merchants of medieval Europe as they sailed out - it from the Black Sea down to the Mediterranean and then clockwise out into the Atlantic, up into the Baltic and distributed it in that fashion.
POINAR: I think it's interesting that the rate at which it spread leads a lot of people to believe that - I mean there are those that it's not Yersinia, because it moved too quickly to be a plague-like outbreak. And those who do believe it's Yersinia, it was like a pneumonic form, right? So it was then eventually transmissible person to person via air, right? And like...
MCCORMICK: What was very - you have to distinguish between long-distance transmission and close transmission.
POINAR: Right, right.
MCCORMICK: The long-distance transmission very clearly follows the shipping schedules.
FLATOW: And just to make sure that people are not panicking now, there is antibiotics that do work against the modern plague, right?
MCCORMICK: That's right. That's right. The - if you're diagnosed with plague you - immediately antibiotics will fix you very quickly.
FLATOW: And did you...
MCCORMICK: Don't delay, though.
FLATOW: Did you find evidence of the rats where you found the bodies for the plague?
POINAR: So we haven't actually specifically targeted that, but that's a very interesting and important question. Of course, you know, Barney Sloane made a very good argument in his recent book that we don't find extensive preservation of rat skeletons in many of these sites and maybe that has something to do with the preservation abilities of the actual rat body as opposed to a human body but...
MCCORMICK: I can address that, if you wish.
FLATOW: Go ahead.
MCCORMICK: I mean, that's an argument that was started in the 1950s, because archeologists were not turning up rats. The first rats were discovered in the late '80s, in fact, in London. And the reason they weren't turning up rats is if you've ever excavated with a trowel, rat bones are extremely small and the chance of turning them up with a trowel are almost zero. In order to find rats, you have to sieve with very fine meshes, and it will take you - two summers ago, I was doing it and found a nice rat jawbone. It can take you, with a quarter of a millimeter mesh, which is what you need to reliably find rat bones, it will take you an hour or two to do a liter of soil. So it's very, very labor intensive however.
POINAR: But actually we should and use the exact same (unintelligible) actually for the DNA of the rat.
MCCORMICK: (Unintelligible) we developed and have a database that you can consult online of many hundreds of archeologically documented rat bones from the 3rd century B.C., up to the 16th, 17th century.
FLATOW: Let me...
MCCORMICK: They're all on the right places now.
FLATOW: All right. Let's go to the phones. Let's go to Alice(ph) in Pacifica, California. Hi, Alice. Welcome to SCIENCE FRIDAY.
ALICE: Hi. I'm wondering if the guests have read Samuel Cohn's work. For example, June 2002 American Historical Review and a book he's written, who conclusively - I think pretty convincingly argues that the Black Death was not bubonic plague, having nothing to do with rats and so forth. And he assembles a big database of, you know, the epidemiology just does not match bubonic plague at all. It hit at the wrong time of the year. The mortality was very different, people acquired immunity. That's why in the 1370s most people who died were infants and young children, because the earlier generation in 1348 had acquired an immunity. He's pretty sure it's viral, but he doesn't know what it is.
So if the Black Death was just not bubonic plague at all and, in fact, was viral and not (unintelligible), it's like...
FLATOW: All right. Let me get a reaction. Michael?
MCCORMICK: I've read Dr. Cohn's work and I'm familiar with it, and I knew his teacher. And it was the teacher, David Herlihy, my predecessor in the Department of History here at Harvard, was the first to throw out that - in very tantalizing fashion, some very stimulating questions which challenged aspects notably of the epidemiology. But I'm satisfied, from my own personal study of the materials that, while it's worthwhile to challenges these questions, the epidemiology of - as reported from medieval resources certainly corresponds to my understanding of the epidemiology, particularly as delineated by the World Health Organization and the Indian Plague Commission.
And I think that the ancient DNA evidence - this is now the, really, the second or third result, positive result of the DNA presence of Yersinia pestis from top - well, very well-regarded ancient DNA labs. And I think now we've reached the point of pretty much conclusion on this part of the debate.
Now, there may well have been other - there certainly probably were other infections that occurred at the same time, but the presence and the role of Yersinia pestis for the Black Death, for the medieval plague - we still don't know about the Justinianic plague that played such a big role in bringing down the Roman Empire. But for the Black Death of the Middle Ages, I think that this part of the debate is closed, and I think it's time to move on to another one.
FLATOW: Well, let's move on to that debate about the Justinian. Why do we know so little about that?
MCCORMICK: Because there's been very little work done on it, and the - that broke out in 542, in, again, in one of the Roman Empire's grape ports and moved from there all around the empire. The problem is that that plague was so devastating - remember that the first outbreak is just the beginning of these pandemics. The medieval plague went - ran into the early 18th century. The Justinianic plague started in 542 and went to 750. It came back, I think, about 15 times over that 200-year period, each time killing between a third and two-thirds of the population.
What happened was that the lights go out. We lose - the number of records being generated by the Roman Empire diminishes tremendously after 542, and so it becomes very, very difficult to follow the events in the written sources. That means that archeology, that means the kind of molecular archeology that Hendrik and his team and that of the results of Stephanie Haensch in October and that Mark Achtman are working on, that kind of molecular archeology really has to be the first line of approach now.
FLATOW: Hendrik, are there any places you could look for?
POINAR: Sure, sure. No, there are remains of that first outbreak.
FLATOW: Is the DNA viable, if you found any?
POINAR: Yeah, yeah. No, that's an important million-dollar question that there are several groups, including ours, looking at. So that's obviously with - I mean, the first, really, place to go right now is using a very similar type of enrichment strategies actually to acquire the entire genome of the Yersinia pestis that caused this outbreak, and then really trying to identify specific mutations within that genome to be able to say something about the increased virulence, or whether or not it wasn't, and whether or not what we're looking is really an syndemic model of infection with many co-circulating things, and it just happened to be a perfect storm, right, we know...
MCCORMICK: Yeah. And let me just point (unintelligible)...
FLATOW: Well, let me just remind - I just have to jump - gentlemen, I got to just jump in here for a second...
FLATOW: ...and remind everybody that this SCIENCE FRIDAY from NPR. Sorry. We're all very excited about - talking about...
MCCORMICK: ...seem to be mutations change over space and time so that it would be theoretically possible, and as indeed was argued in the October paper in PLoS Pathogens, that one can actually detect different variants of the - in the genome of the disease as it moves through the population. So you could say that this person died at the beginning of the outbreak, this person died at the end. You could say that this person died in the third wave, this person died in the fifth wave, which would just be a radical transformation in our knowledge of the historical epidemiology of this terrible disease and, of course, of the shipping and communications that made it happen.
FLATOW: Let's go to the phones. One - let's see if we can get a call in here from Juan in San Antonio. Hi, Juan.
FLATOW: Hi there.
JUAN: I just had a quick question. Basically, since the plague, at least Yersinia pestis, when it's related to flea bites, takes a while to incubate, but does kill you quickly. What are the - you all suggest - that transformed it from the flea-ridden plague to a pulmonary plague, which is a hemorrhagic pneumonitis that tends to kill people within 24 hours? If you can shed some light on that.
FLATOW: So you think it might have transformed into a different one and so that's why it killed so...
JUAN: I'm wondering about that because the vectors - you know, the way it transmits is very different...
JUAN: ...and also the way it eventually takes its toll on the human body.
JUAN: Basically pneumonia-wise, it's just basically hemorrhagic pneumonitis, destroys capillaries and infiltrates the lungs.
FLATOW: OK. Let me get a quick answer. Thanks for the call.
MCCORMICK: Yeah. I think one of the - I mean, really, hence why I keep, sort of, emphasizing that, really, the next step is acquiring an entire genomic analysis. And it doesn't seem impossible using this type of sort of enrichment technology to get that. And with that information, hopefully then one has a better idea as to, are there specific genes that had been modified, or are there upstream or downstream regulators that have changed to add expression levels of certain proteins, which might explain this increase virulence in rapid transmission.
FLATOW: Mm-hmm. And I got about a minute left, but I want to get an interesting fact in here I know. Talking about - Hendrik, how does a flea actually transmit the plague?
POINAR: Well, that's interesting. So the - once it becomes infected with the Yersinia pestis, the bacteria starts replicating in its gut and causes a regurgitation of everything - the blood meal that the flea takes. And so the flea becomes increasing panicked and hungry and transfers from host to host. And each time it takes a new blood meal, it regurgitates thousands and thousands of bacteria that had been replicated within in the flea back into this new wound within the individual. So it's actually regurgitating its previous meal, which, of course, contains the Yersinia pestis, thereby transmitting it to the human and then, of course, jumps onto another host and so on and so forth.
FLATOW: Let me talk a little bit, in a minute we have left, about what you called the modern plague. Is it really a plague or is it just a few cases of plague in the Southwest, Michael?
MCCORMICK: Oh, well, it's well under control in the Southwest. I mean, it is endemic among prairie dogs. And because there is an excellent public health organization of surveillance there, it is under control. One can easily imagine that when the institutions that keep an eye on our public health are in jeopardy, it could once again get out of control. The last great outbreak - well, it breaks out regularly in India and Madagascar still today and there are great efforts to enhance the public health efforts there. Wars and upheavals are usually very good things for Yersinia pestis, because they disrupt the institutions that keep an eye on it.
FLATOW: And so does tax cuts, I imagine.
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FLATOW: Yeah. When you don't have enough money to take care of local health systems.
MCCORMICK: Yes. For example, the public health.
FLATOW: Yeah. Thank you, gentlemen. Quite interesting. Thank you very much for taking time to talk with us.
MCCORMICK: Thanks for having me, Ira.
POINAR: You're welcome. Thank you for having us.
FLATOW: You're welcome. Hendrik Poinar is an evolutionary geneticist at the Michael DeGroote Institute for Infectious Disease Research in the Department of Anthropology at McMaster University in Hamilton, and Michael McCormick, chair of the Science of Human Past program at Harvard in Cambridge. He's also the Goelet professor of medieval history there.
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