Profiling the perpetrators of past plagues

 From the Black Death to the Spanish flu, waves of infectious disease have repeatedly laid waste to human populations. Scientists from many disciplines have long been intrigued by the possibility of disclosing the exact identity of the responsible pathogens and figuring out what made them so deadly. Yet even after sequencing ancient DNA became possible, the omnipresence of microbes made it challenging to pinpoint the historical culprits.

One of the pioneers of the field of microbial archaeology is geneticist Johannes Krause, founding director of the Max Planck Institute for the Science of Human History in Jena, Germany. Earlier this month, he published a paper in Nature Communications tracing the spread of the Black Death, which killed half the European population — 30 million to 50 million people — in less than five years, starting in 1347. Krause and coauthors examine the challenges and revelations to be had in exploring ancient pathogens in recent issues of the Annual Review of Microbiology and the Annual Review of Genomics and Human Genetics.

This interview has been edited for length and clarity.

The job of the average archaeologist, to uncover the ancient remains of humans and all of their artifacts, is hard enough. But how do you find microbes that infected people thousands of years ago?

We extract all the DNA we can get from those same human remains, often fossilized teeth or bone, and we sequence it. This allows us to distinguish human DNA from the DNA of the pathogens we’re looking for, and then to try and reconstruct their genomes. This way, we are building a molecular fossil record that can tell us how pathogens have changed through time. And that provides important information about the biology of the microbial villains that have caused major epidemics in the past.

Ancient DNA is often highly fragmented. How do you know which bits of the genome go where?

There are different ways of doing this. You can try to let the computer put the pieces together based on overlaps. But like a jigsaw puzzle, that can be challenging when pieces are missing. So that’s when we need to look at the puzzle box, so to speak, and try to fit the fragments to the DNA of a modern relative instead. Which means it is as good as impossible to discover a new species, or to recognize a species with genes that mutate very fast, as the sequences may have changed so much we have no idea what it is.

The first thing many people might think of when they hear the words “microbial” and “archaeology” in the same sentence is pathogens escaping from ancient graves, “curse of the pharaohs ”-style. Is this something you need to take precautions for?

It is certainly something we thought about early on. There have been some studies, in the 1980s, where people tried to grow ancient bacteria or viruses. But nobody has been able to revive a pathogen that is more than a hundred years old, so I think it is very unlikely that this will happen.

There also is not a single case in which anybody got infected from an old skeleton, and there are thousands of archaeologists and anthropologists in the world handling ancient human bones on a daily basis. These people often don’t use gloves, and some of them even touch tiny fragments with the tongue to find out whether the fragments are made of stone or bone — bone is a spongy material, so it will take up liquid from your tongue and stick to it.

The pathogens really appear to be as dead as the person is. […]

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