Researchers Uncover The Truth Behind The World’s First Plague Pandemic

A depiction of a person suffering from the Justinianic Plague.

Over the course of history, there have been many devastating pandemics, from the Black Death in the 14th century, which wiped out an estimated 75 to 200 million people across Eurasia and North Africa, to more recent outbreaks such as COVID-19 and the Spanish Flu in 1918. The Black Death is arguably the most famous pandemic ever, having been caused by the plague—specifically, the bubonic plague. However, few know that the plague had actually started long before that. Known as the Justinianic Plague, the plague first spread around during this pandemic, and it swept through the Byzantine Empire from 541 CE to 750 CE. Unlike what we saw with Black Death, the Justinianic Plague lasted for over 200 years, primarily as a result of widespread trade, poor immunity, and a lack of coordinated efforts to stop it from spreading.

While we have many details about the plague’s impact on society, historians and scientists have, for centuries, puzzled over what exactly caused the Justinianic Plague. It killed tens of millions, reshaped societies, weakened empires, and left a lasting mark on human history, yet we had no clue about what pathogen was responsible for all of it. Until recently, direct and definitive genomic evidence of what caused this catastrophe was missing, but now, a groundbreaking discovery by researchers from the University of South Florida (USF), Florida Atlantic University (FAU), and international collaborators has solved this mystery. While past studies have already shown evidence for the cause of the Justinianic Plague, they’ve always faced criticism and rejections from some scientific communities due to the methods and technology used. This team with researchers from USF and FAU, however, utilized much more reliable, sophisticated, and definitive tools and methods for analyzing DNA, gaining approval from all scientific communities. They found the DNA—direct genomic evidence—of the pathogen responsible for the Justinianic Plague in 1,500-year-old teeth from a mass grave in Jerash, Jordan. After thorough examinations, they’ve confirmed that the Justinianic Plague was caused by Yersinia pestis, the same bacterium behind later plague pandemics like the Black Death. Given that many historical accounts of the Justinianic Plague describe its symptoms in a way that is very similar to the symptoms reported during the Black Plague, this makes even more sense.

The Justinianic Plague: A Historical Catastrophe

The Justinianic Plague, also known as the Plague of Justinian, was named after Byzantine Emperor Justinian I, since it began in 541 CE, when he was still emperor. It broke out in Pelusium, a port city in Egypt, but the bacterium that caused the outbreak may have actually originated from China or India and arrived in Egypt via trading routes. From there, it spread quickly across the Eastern Roman Empire, eventually reaching major cities like Constantinople. According to historical accounts from witnesses, the Justinianic Plague was a terrifying disease that caused fever, swollen lymph nodes, and often death within a matter of days. Estimates suggest that the Justinianic Plague may have killed up to 10% of the world’s population and 20-40% of Constantinople, the capital city, by the time it came to a complete end. Over 200 years, as the plague came in wave after wave, tens of millions of people passed away. Many towns were abandoned, trade slowed down, and the Byzantine Empire weakened. The plague set the stage for major shifts in Western civilization.

A Breakthrough in Jerash

The former Roman hippodrome in Jerash, Jordan.

In two studies published in Science Advances (Jiang et al., 2025), researchers confirmed the first definitive evidence that Yersinia pestis caused the Justinianic Plague. The team, which was led by Rays H.Y. Jiang from USF and Greg O’Corry-Crowe from FAU, analyzed human teeth from a mass grave under the former Roman hippodrome in Jerash, Jordan, a major trade hub just 200 miles from Pelusium. The hippodrome was once a place for chariot races and entertainment, but due to the high number of deaths during a deadly outbreak between 550 CE and 660 CE, it was later repurposed as a burial site.

Almost 1,500 years later, the team of researchers visited the hippodrome to make breakthrough discoveries regarding the Justinian Plague. According to O’Corry-Crowe, the team used “targeted ancient DNA techniques [and] successfully recovered and sequenced genetic material from eight human teeth excavated from burial chambers beneath the former Roman hippodrome in Jerash.”  They found nearly identical strains of Yersinia pestis in the remains, confirming the bacterium’s presence at the heart of the Byzantine Empire. This exact genetic match suggests a fast-spreading and deadly outbreak, which matches historical descriptions of the plague. “This discovery provides the long-sought definitive proof of Y. pestis at the epicenter of the Plague of Justinian…Our findings [offer] the first direct genetic window into how this pandemic unfolded,” Jiang said.

The Jerash site also reveals a lot about how ancient societies coped with disaster because in a matter of a couple decades, the vibrant city of Jerash turned from a place of celebration into a mass cemetery, thus showing how overwhelmed urban centers were by the plague. This really helps highlight the chaos and desperation that was caused by the world’s first known plague pandemic.

The Plague Through Time

A companion study conducted by the same team placed the Jerash findings in a broader context. They compared hundreds of ancient and modern Y. pestis genomes, including those from Jerash, and they learned that the bacterium had actually been circulating among humans for thousands of years, long before the Justinian Plague. Unlike COVID-19, which spread from a single animal-to-human spillover, plague pandemics emerged repeatedly from animal reservoirs, like rodents, in different regions and eras. The Justinianic Plague, the Black Death of the 14th century, and even modern cases share this pattern of recurring outbreaks.

Today, Y. pestis still circulates in parts of the world, but there’s nothing to worry, as it is quite rare. In July 2025, a person in northern Arizona died from pneumonic plague, the deadliest form. This marked the first U.S. fatality since 2007. 

The Justinianic Plague was a turning point in history, and the researchers’ discovery finally put an end to the centuries-long search to find the definitive cause of the Justinianic Plague, helping us map out the history of the plague. While the Black Death is regarded as the greatest plague pandemic, we can now confidently label the Justinianic Plague as the world’s first plague pandemic.