The Silk Road, a network of land and sea trade routes that connected China and the Far East with Europe from 130 B.C. to A.D. 1453, became a vital source for everything from fabric and leather goods to spices and precious stones. It connected communities and allowed them to share innovations such as paper-making and printing technology, as well as language, culture and religious beliefs.

But the medieval superhighway also has a darker, lethal legacy: It enabled one of the first great pandemics—the plague known as the Black Death—to spread along its route and eventually reach the edge of Europe, where it killed more than 50 million people between 1346 and 1352.

“The Silk Road allowed, possibly for the first, the sustained transmission of diseases endemic to Central Asia to move out along the Road to Europe,” explains Mark Welford, a professor at the University of Northern Iowa and author of the 2018 book Geographies of Plague Pandemics.

As Welford explains, one reason the Silk Road was so effective in aiding spread of disease-causing microbes was that, despite its name, it wasn’t just a single route. The overland portion of the Silk Road was actually a set of paths that split and reconnected across the steppes of Central Asia, almost like the blood vessels of the human body or the veins in plant leaves.

Along that network there were various stops—villages, towns and outposts called cavaranserais—scattered about a day’s hike apart. Few travelers covered the Silk Road’s expanse, which stretched for thousands of miles from East Asia to Turkey. Instead, caravans of traders and camels traveled back and forth between the local nodes, trading their wares for other goods, gold or money, and then returned home. (Here’s a map of the basic route, from The Miami University Silk Road Project.)

In the process, the traders and their animals also passed along contagions, which spread slowly and gradually between points along the Silk Road. As bad luck would have it, the route also brought travelers in close proximity to what some researchers point to as a source for a particularly dangerous disease.

In a 2015 study, Norwegian and Swedish scientists proposed that fluctuations in the climate of the Central Asian steppes caused the region’s rodent population—probably gerbils and marmots in particular—to crash. That, in turn, may have forced fleas that carried the bacterium Yersinia pestis, which causes plague, to leave their rodent hosts and find new places to live, such as camels and their human owners. After several years of flea relocation, as the scientists’ theory goes, it took another decade for the caravans to gradually advance the plague westward, until it reached the edge of Europe.

Kaffa, a Crimean Black Sea port now known as Feodosia, “seems to be the jumping off point for the primary wave of the medieval Black Death from Asia to Europe in 1346-7,” Welford says. “Genoese or Venetians left Kaffa by boat, infected Constantinople and Athens as they made their way to Sicily and Venice and Genoa. But I suspect [Black Death] also made it to Constantinople via an overland route.”

One famous 14th-century account claimed that plague was introduced to Kaffa deliberately, through a Mongol biological warfare attack that involved hurling plague-infected corpses over the city’s walls.

Whether that actually happened, the plague eventually became a disaster in the East as well as in the West. “It killed off many of the Mongol rulers and other elite, and weakened the army as well as the local economies,” explains Christopher I. Beckwith, a distinguished professor at Indiana University Bloomington, and author of the 2011 book Empires of the Silk Road. It’s estimated that the Black Death killed 25 million people in Asia and North Africa between 1347 and 1350, in addition to the carnage in Europe.

A 2019 study by German researchers genetically linked the Black Death to an outbreak that occurred in 1346 in Laishevo in Russia’s Volga region, raising the possibility that the disease may have spread from Asia by multiple routes.

In any case, when the Black Death reached Europe, it attacked a population that already was weakened and malnourished by the brutal nature of the feudal economy.

“I think a good argument can be made that [Black Death] hit at a time when the health of the poor was compromised by the stress of famines, poverty and the very nature of serfdom,” Welford says.

In The Decameron, written in 1352, Giovanni Boccaccio describes the Black Death, which reached Florence in 1348. Victims first developed a swelling in their groins and armpits, after which the disease “soon began to propagate and spread itself in all directions indifferently; after which the form of the malady began to change, black spots or livid making their appearance in many cases on the arm or the thigh or elsewhere, now few and large, then minute and numerous.”

Between March and July of that awful year, Boccaccio noted that more than 100,000 of the city’s inhabitants died, their bodies piled outside doorways. Grand palaces and stately homes where the nobility and their servants had dwelled were left empty, so that the city was “well-nigh depopulated.”

Without modern scientific knowledge and antibiotics, Europeans struggled by trial and error to find ways to fight the bacterium’s wrath. “The waning of the Plague occurred because of the combined use of quarantine, lazarettos, plague hospitals and rudimentary use of masks by medics, the establish of health-cordons and the shutting of borders, and use of health spies to forewarn countries of impending plague surges,” Welford explains.

But the Black Death wasn’t completely over. Different strains of the same bacterium returned to ravage Europe and again and again until the 1700s. Additionally, as Science magazine reported in 2016, researchers found that a strain of the disease that developed in Europe eventually made its way eastward, and killed millions of people in China in the 1800s.

The spread of the Black Death coincided with the beginning of a smaller, more connected and integrated world, thanks in part to the Silk Road. Along its routes, microbes spread as readily as people, inventions and ideas.