Black Death’s DNA Decoded Using Teeth From London’s ‘Plague Pits’

BY Jason Kane  October 13, 2011 at 3:04 PM EDT

Illustration of the Black Death from the Toggenburg Bible

An international consortium of researchers announced this week that they’ve managed to reconstruct the genome of Black Death — the “great-grandmother” of modern plagues and the same illness that wiped out around half of Europe in just a few years in the mid-1300s.

The development marks the first time an ancient genome has been sequenced, according to a report published online Wednesday in the journal Nature.

Beyond providing a clearer snapshot of why this particular bug rampaged through Europe with such ferocity 660 years ago, the sequence opens the door to a world of research that could change the game in modern pandemic studies. Comparing the blueprint of the ancient bug with its modern ancestors could allow scientists to trace the plague’s evolution and virulence over time.

The mapping effort comes on the heels of another breakthrough by the same team — a consortium led by researchers at McMaster University in Canada and the University of Tubingen in Germany. Using samples from the dental pulp of victims buried in mass graves in London’s “plague pits,” they developed a new approach to pulling out degraded DNA fragments and pinpointing a specific variant of the Yersinia pestis bacterium that was the root cause of the plague.

Now that the entire genome has been mapped from that DNA, it’s clear that there have been relatively few changes to the structure of the bug in the last several hundred years. McMaster University geneticist Hendrik Poinar explains what that means and how it could impact the study of pandemics in the future.

Why would you want to map the Black Death?

HENDRICK POINAR: First of all, we wanted to understand more about this bacterium, the pathogen that was responsible for this massive killer that wiped out 30 to 50 percent of the European population between 1346-1353. If we could get access to the whole genome, we thought we might be able to explain why mortality rates in modern-day plagues are relatively minor when compared to that of the Black Death. There are still outbreaks of the plague today, which kills about 2,000 people per year, but the modern flu season kills more. So if the plague killed tens of millions of people across five years at a time when travel was nothing like today, why was it such a deadly pathogen? And are there intrinsic factors within the genome that would give us hints to that? We’re very interested to know how things have changed over time — the co-evolution of both the host (human and rodent) and the pathogen.

Even before humans left Africa, we had been in direct contact with pathogens. But those that have been particularly virulent — things such as the plague and AIDS — have become less virulent. If these pathogens are going to use us as a host over a long period of time, they can’t completely kill us. There needs be an evolutionary way to maintain the pathogen but still keep the host alive. So we’re very interested to know how that change works.

And what did you learn about changes over time to the plague?

POINAR: When we look at changes in the ancient bug, at the onset, there are no smoking guns in this genome that would suggest that there’s something intrinsic to it that made it so virulent. There’s nothing absolutely different or novel in the ancestral bug. The bulk of the genomic changes that are involved in virulence remain about the same. They’re still present in the descendents of the original pathogen. Antibiotics like tetracycline and fluoroquinolones are effective today at killing these bugs and they would have defeated the Black Death back then, too. But what we don’t see in the modern form of these bugs is the same combination of changes. And we don’t know if the combination of changes is what’s responsible for the virulence.

How does this ancient disease relate to other modern pandemics?

POINAR: Basically if we deduce that the virulence is not increased in the ancient pathogen, then it really shifts the focus back to the fact that it’s the whole context of a situation that counts. It’s not simply a “pandemic,” but rather its a “syndemic.” It’s not just the bug itself but the climate, population density, age distribution, whether people are facing other immune-compromising pathogens. So if we go back to 1348, to downtown London, we’re sitting in a densely packed area, the climate’s just starting to drop — with temperature 4 to 6 degrees cooler than they had been in previous years, rains have started and haven’t stopped, food is in limited quantity, population numbers are very high, winters are cold. And all of a sudden, the arrival of a new pathogen from the east and it all adds up to the perfect storm. Part of it’s the bug, part of it’s the human host, but a lot of it has to do with a lot of other contextual factors. If we can come to that conclusion by looking at the gene itself and learning something about its increased or decreased virulence over time, that might help us be better prepared for other outbreaks.

Can we learn anything else by looking at the genomics of the Black Death?

POINAR: This bug is the great-grandmother of all modern strains of the plague. If you take 20 strings that are all tied together at one end, the tips of the strings would represent the modern versions of the plague that we see today in places like Africa, South America, Colorado. And the knot that binds them all together at the other end is the Black Death. They all have a root at this knot. If we step back further from that knot, the only ancestor is a version of the disease that we saw in rodents. And the genetic changes that occurred from the rodent pathogen to the human pathogen might tell us a lot about how disease spreads between species. What is it about those changes in that small amount of time that allowed the bug to adapt? And can we use that as a model to study other disease? That’s what we’ll be looking into next.

For more on the study, watch this video from Nature:

On Thursday’s NewsHour broadcast, Poinar will discuss the project with Ray Suarez. Be sure to tune in.