"This city, whose crowded streets we could barely pass through … is now delivered up to solitude, to silence, to indigence, to desolation, to death."
So said Henri de Belsunce, Bishop of Marseille, when describing the effects of a plague epidemic that devastated the French port between 1720 and 1723. It was one of the last major outbreaks of the disease to strike Europe and it was a particularly bad one, claiming an estimated 100,000 lives – half in Marseille itself and the rest in neighbouring cities and the countryside of Provence.
Now a genetic analysis is shedding light on the source of that outbreak with surprising implications.
Based on fragments of plague DNA recovered from the teeth of five victims in a Marseille grave, researchers say the plague of the 1720s is a direct descendant of the infamous Black Death that wiped out millions of Europeans during the 14th century.
The finding suggests that the Black Death never really died out, but instead lay dormant in some hidden reservoir over the centuries, popping up from time to time when conditions allowed. Traces of it may still linger somewhere near the Mediterranean region today.
"For 400 years, we had plague epidemics in Europe that repeatedly went away and resurged," said Hendrik Poinar, an evolutionary biologist at McMaster University in Hamilton and a co-author of the study, currently under review by the online journal eLife.
"These data would seem to suggest that there was a source of plague with easy access to Mediterranean ports that was seeded during the Black Death and remained relatively local," he added.
Precisely where that hidden source existed remains a mystery. The authors speculate it could be anywhere in Europe or western Asia, which would periodically allow it to hitch along common trade routes.
By comparing the DNA of different strains of plague preserved within teeth, scientists have been working to trace the evolution of Yersinia pestis, the bacterium behind the disease. Historically, it is one of the world's deadliest and more persistent pathogens – and one of the best for understanding how human populations responded to epidemics before antibiotics came on the scene.
The germ makes its home in rodent populations and is transferred to humans by fleas. Once it has made the jump between species, it can spread from person to person. In 2008, microbiologists discovered that the bacterium can also hunker down in soil for months and remain viable.
Researchers generally agree that plague originated in Asia. Europe's two worst plague pandemics – the Black Death and the earlier Plague of Justinian, named after the sixth-century Byzantine emperor – are thought to have arisen when particularly aggressive Asian strains broke into Europe.
But there is ongoing debate about how and why additional outbreaks re-emerged for centuries after the Black Death pandemic.
Last year, a Norwegian-led team proposed that the succession of European outbreaks between 1300 and 1850 represent separate pulses of plague that were triggered when climate fluctuations in Asia affected rodent populations and brought humans in contact with the disease. In that scenario, each pulse surged westward along the Silk Road, taking about 12 years to reach and reintroduce plague to Europe.
The new study contradicts this by demonstrating that the plague that crippled Marseille in the 1720s is too closely related to the Black Death strain to represent a separate wave.
Boris Schmid, lead author on the Norwegian study, said that the two could still have arisen from a localized western Asian source, though, he added, "for our hypothesis to hold, the reservoir should not be too close to Europe," because it would not explain the time delay between climate fluctuations, as recorded in tree rings, and plague outbreaks.
Dr. Poinar said a source in or near Europe is more likely, but data are needed from other outbreaks to learn more. He and his colleagues recently received permission to obtain samples from a Mamluk cemetery in Egypt, which could reveal more.
The broader effort to uncover how strains of plague relate to each other should also shed light on the third pandemic that began in China in 1855 and crossed the Pacific to California, where it can still be found in the wild rodent population – and last summer was responsible for a partial shutdown of Yosemite National Park after two visitors contracted plague there. Recent work suggests the third pandemic might also be a reboot of the Black Death that reflected back to Asia from Europe.
Although plague outbreaks can be managed, the disease continues to pop up. Between 1,000 and 2,000 cases are reported to the World Health Organization each year.