A Revolution Is Sweeping the Science of Ancient Diseases

The study of DNA from millennia-old bacteria and viruses is revealing new secrets about the plague and other epidemics.

Black and white photograph of a skull
Getty / The Atlantic

When Johannes Krause was a graduate student working on the Neanderthal genome in the 2000s, so much of the DNA recovered from the ancient bone fragments came from everything else: the skin cells of excavators and scientists, the bacteria on those humans, the microbes in the soil. To get to Neanderthal DNA, you had to junk the rest. Once scientists figured out how, they rushed to sequence not just Neanderthal DNA but also ancient human DNA, which together have been rewriting the early history of our species.

Only later did scientists realize that there is gold in the “junk” too.

If you know exactly how and where to look, you can also find DNA from ancient pathogens in old bones. The “junk” might actually contain clues about long-ago pandemics. Over the past decade, scientists have used ancient DNA to study diseases including the plague, syphilis, hepatitis B, and a mysterious “cocoliztli” epidemic—all using techniques honed through decoding the Neanderthal genome. A boom in ancient pathogen DNA is uncovering hints of forgotten and even extinct diseases.

Krause, now the director of the archaeogenetics department at the Max Planck Institute for Evolutionary Anthropology, is a co-author of the recent book A Short History of Humanity, with the German journalist Thomas Trappe. I’ve written about Krause’s studies as they’ve come out over the years, but the book synthesizes two decades of work with ancient DNA, human and pathogen. This kind of research is difficult; it relies on a very small number of samples and requires the expertise of historians and archaeologists to interpret. And even then, some things about the past are unknowable. Amid our current pandemic, I spoke with Krause about some of the most intriguing yet puzzling genetic clues we now have about very old pandemics.

This interview has been condensed and edited for clarity.

Sarah Zhang: A lot of your work on ancient pathogens has relied on old teeth. Why are teeth so good for this?

Johannes Krause: Blood is what we’re actually looking for, because most of the pathogens we’re looking at—hepatitis B or Yersinia pestis—they are actually blood-borne. But how do you get a blood sample from 600 years ago? The tooth is the best place for blood samples because teeth are vascularized, so you have blood flow inside the teeth. And the teeth are protected by the enamel. They’re like a little time capsule.

Zhang: How much of the tooth do you need?

Krause: Usually really tiny samples. We take an average of about 50 milligrams. It’s like a bread crumb. Usually what you do is you cut off the crown of the tooth, and then you drill inside the crown, which is where the pulp chamber is. That’s where the dried blood vessels of the tooth would be.

Zhang: Did you ever think that you would accidentally become a dentist for ancient teeth?

Krause: It was kind of strange. When you’re doing the sampling, it often smells like the dentist’s. I started to realize I was doing something very similar. [Laughs.] I hated the dentist when I was young. Who likes them? But I kind of know quite a bit about all the names of teeth, like the P1, P2, the M1, M3, and things like that. When I go to the dentist, the dentist is always amazed.

Zhang: In 2011, you and your colleagues published the first genome of plague bacteria, Yersinia pestis, from the teeth of medieval Black Death victims. But for a long time, Yersinia pestis and the plague had been suspected but not confirmed as the cause of the Black Death. What did you find in the DNA?

Krause: When we started, many historians were discussing whether the Black Death was caused by the plague. People said it was a virus. People said it was a hemorrhagic fever. Some people were saying it’s anthrax; other people were saying it’s an unknown disease. And we just said, Yeah, let’s look. We had access to this cemetery that was only used in the Black Death, which is perfect. When they had thousands and thousands of dead people in London, they just turned part of the city into graveyards. And the East Smithfield, which is close to the Tower of London today, was such a grave site.

We did the genome, and it worked surprisingly well. One of the first discoveries is that it didn’t have what we would call a “derived mutation” or a gene or even a position in its genome that is specific to the Black Death. Today, plague is still found in nearly every continent. We found that the Black Death is literally the common ancestor, the mother of 80 percent of the strains that circulate in the world today. And that’s pretty important, because it tells us that, biologically, the Black Death strain was not special. It’s not that it was more infectious, more virulent. It’s actually more or less what you have circulating today in the Grand Canyon in squirrels or in groundhogs or what you find in Madagascar.

Zhang: This is what I find so fascinating. If the bacteria are largely the same, why don’t we have Black Death anymore or big outbreaks of bubonic plague?

Krause: First of all, we changed our lifestyle quite a bit. We are just living in much more hygienic conditions. Plague is actually not usually transmitted between people, but between animals and people, and usually the vector is a flea. We don’t live with mice and rats in the house as much.

Also, the type of rodents changed. In the medieval time, when the Black Death happened, we had a very large population of black rats—much, much bigger than today. And in fact, they were largely replaced by brown rats, Rattus norvegicus. Now, brown rats are very different in their behavior. They live in the sewage, and they live in the ground. They don’t live under the roof. The black rat was called the roof rat. They were living where people stored their grain, and when people still had the grain storage in the house, that’s where the rats were.

But people that do have exposure to animals, like people that live in the countryside, people that go hunting, they are usually the people that contract plague these days. There’s several cases in the U.S. every year. And there are warning signs if you go to the Grand Canyon: Don’t feed the squirrels, because you could get plague. It’s actually moving in the U.S. from the West Coast to the East Coast with rodent populations.

Zhang: I live in New York, so I guess we have that to look forward to at some point.

Krause: And you have a lot of rats in New York.

Zhang: Yes, but they’re brown rats!

Krause: Fortunately, yes.

Zhang: The spread of brown rats through global shipping routes is one of the big ecological stories of the past several centuries. Environmentally, it’s been devastating, especially for a lot of island ecosystems, so it’s really interesting to think about the role they might have played in spreading disease—or not spreading it.

Krause: Some people speculate that the brown rat saved us from the plague. One of the mysteries is that the plague disappeared in the beginning of the 18th century, when you still have rats, when you still have hygienic conditions which are not great. What happens in Europe is that the new rat gets introduced. The brown rat arrives—there’s some historical documentation around the 1720s—and then it starts spreading. Actually, wherever the brown rat moves, the black rat is getting replaced, because they are really aggressive toward black rats. The black rats disappear. It’s ironic, almost, that people, when they see rats today, they think about the plague and How horrible. But maybe that rat that you see today, like in New York in the subway, is actually the one that saved us from the plague.

Zhang: I think this really speaks to how disease is contingent on human behavior. We might think of diseases as things that just exist in nature—they’re out there and they’re trying to kill us. But what’s happening is that these pathogens are only successful if they find and exploit the seams in human behavior. We created the conditions for the plague because we started living in cities, because we started living with rats, because we have fleas.

Krause: Absolutely, we are creating the niche for those pathogens. We ourselves only became an interesting host in the last 10,000 years, when we started agriculture and having large populations and a sedentary lifestyle where we live with a lot of people in the same place and dump our excrement behind our houses. Basically we are surrounded by garbage, and that attracts a lot of rodents and potential parasites of those rodents.

It’s only from that point, where the population size is big enough, that infectious disease can spread and can be passed on between one population and another—only then it becomes a human pathogen. We’ve become even a better and more interesting host, like we've seen with coronavirus, right? It took three weeks, and it was in almost every country in the world.

In the book, we say humans have become like bats because we now have dense populations. Bats live in these really dense populations, like millions sometimes in one cave. But unlike bats, we have only had 5,000 years to adapt, and bats have done that for the last 40 million years. But we have our big brains and really powerful medicine.

Zhang: Yeah, the plague–or some form of it—seems to have existed in the Stone Age too. You and your colleagues and others have found evidence of bacteria that looks like Yersinia pestis in teeth going back nearly 5,000 years in Europe. But it also looks very different from modern plague, right?

Krause: It is different, and I am still not quite sure what it is and what kind of disease it’s causing. I’m pretty certain it’s lethal, because we find it in high concentrations in the teeth, and then it has caused some sort of sepsis, and it has somehow killed those people. But how it actually enters the blood, we don’t know.

It basically cannot be transmitted by fleas. It lacks the genes that are necessary for flea transmission, which is a very nifty mechanism: Fleas get the bacteria, they clog the stomach of the flea, the flea starves, and then it keeps on biting. Every time it bites, it infects. ˜This whole nifty mechanism, we could show, only evolved about 4,000 years ago. This earlier form, which we call Stone Age plague, doesn’t have that.

So how does it get transmitted? One explanation could be pneumonic, so it’s droplet infection. People cough on each other and inhale and then get infected in their lungs. The most likely other possibility is some sort of enteric fever, like something that is maybe gastrointestinal. They ingest and then maybe pass it on like typhoid fever.

What’s most striking for me is that it was all over Eurasia at that time. We find it in Siberia. We find it in Iberia. And it was somehow related to this highly mobile lifestyle, probably related also to herding. It’s not really what you would expect for plague later on, which occurs in settlements and cities.

Zhang: Have you thought about what kind of mark the coronavirus pandemic could leave in the archaeogenetics record—if any?

Krause: I mean, not that much, right? Much of it is a cultural response that wouldn’t really preserve that well. But maybe people will also see a change in our behavior. You could have the drop in carbon-dioxide emissions over that year. Mortality is high, relatively, compared to other respiratory diseases, but it’s not, of course, comparable to the Black Death. But last year, when people were doing mass graves in New York City, the image is really burned in my brain. It looks like East Smithfield. It looked the same. It was a long, long, long trench where they had put one grave after another.