Historic spread of plague mapped through DNA

GENETICS AND world history have merged in a remarkable research project that maps the distribution of plague around the globe…

GENETICS AND world history have merged in a remarkable research project that maps the distribution of plague around the globe.

DNA analysis has allowed scientists to detail how the dreaded disease spread – but also how it was connected directly to events in recorded history.

The story tells of expeditions along the Silk Road trade routes linking Asia and the Mediterranean. It describes how Chinese efforts in the 1400s to develop sea-based trade helped spread the plague far and wide. And it catalogues the near destruction of European civilisation caused by the Black Death.

A University College Cork-based scientist, Prof Mark Achtman, led the international effort, which also involved scientists in Germany, France, China, the UK, Madagascar and the US.

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Details of their findings are published this morning in the journal Nature Genetics. The work represents the culmination of 12 years of research into the bacterium that causes plague, Yersinia pestis, explained Prof Achtman, of UCC's Department of Microbiology. He is also a Science Foundation Ireland investigator at Cork's Environmental Research Institute.

Reference to plague often evokes images of the Black Death, which swept away up to 100 million lives between 1347 and 1351. The disease was much older, however, and can be traced back about 2,000 years to an origin most likely in China, Prof Achtman said.

The study, which relied on a detailed DNA analysis of Y pestisisolates held in labs around the world, takes on added importance given that plague remains active today.

The disease is still very much with us, Prof Achtman said. “People don’t realise that. It isn’t causing a huge number of cases but it is causing panic” in places where an outbreak occurs, he noted. Flare-ups occur all around the world. “Algeria has intermittent cases of plague, and Kurdistan. In Africa it is endemic.” And even in the US between 20 and 30 cases are recorded each year.

The research goal was to find plague samples from around the world and pick apart their DNA. It was a huge project that could only have been completed through collaborative research, Prof Achtman said.

The work was made more complex given the risks of terrorism. The US had many isolates available for analysis but would not allow the movement of plague samples either in or out of the country, he said. “We had all the different labs and access to DNA but we couldn’t ship it.”

The group ended up with a massive amount of data, however, including 17 complete plague genomes. They were also able to set up direct comparisons between 286 isolates, looking at 933 specific DNA segments or “snips”.

This wealth of genetic data was matched up with historical records to try to understand how the plague managed to spread so readily from country to country and jump to distant continents, Prof Achtman said.

The Silk Road became a major conduit, bringing strains of plague from Asia into Europe. There were several waves, including the devastating Justinian’s plague between 541 and 767 and the infamous Black Death from 1346.

The explorer Zheng He set out on a series of expeditions to open up world trade with China between 1409 and 1433. The voyages involved up to 300 ships and these undoubtedly carried rats infested with the fleas that could spread plague.

“Merchant shipping distributed it all over the world,” Prof Achtman said. “We can map the individual routes of the isolates. [The history] all fits exactly with the genetics. The more we looked at the movement of ships, the more it all fitted.”

The first US exposure came in 1899, according to records which told of a Hong Kong plague ship that docked in Hawaii and then San Francisco. Plague soon spread eastward across the US. Five strains have been isolated since 1939 in central California.

Today plague is readily treated with modern antibiotics, but the disease has not gone away, he said. The study provides valuable information about the infection, and potentially its source.