New USF-FAU Study Redefines Origins of the World’s First Pandemic

For the first time, scientists have unearthed direct genomic evidence of the bacterium responsible for the Plague of Justinian, the earliest recorded pandemic in human history. This milestone discovery was made in the Eastern Mediterranean, specifically in the ancient city of Jerash, Jordan—close to the historical center of the pandemic that devastated the Byzantine Empire nearly 1,500 years ago. The groundbreaking research was carried out by an international team led by the University of South Florida (USF) and Florida Atlantic University (FAU), with key collaborators from India and Australia, who identified DNA traces of Yersinia pestis, the causative agent of plague, in skeletal remains within a 6th-century mass grave.

Historians and scientists have long debated the true cause of the Plague of Justinian, which ravaged the Eastern Roman Empire between AD 541 and 750, causing widespread mortality and profound societal upheaval. Until now, direct biological evidence linking Y. pestis to this catastrophic event had eluded researchers, despite working with indirect indicators such as historical texts and epidemiological patterns. The genomic data extracted from human teeth excavated in Jerash provide the first unequivocal proof of Y. pestis presence in the pandemic’s epicenter, filling a conspicuous gap in the understanding of ancient pandemics and their microbial etiology.

The Jerash excavation revealed a mass burial site beneath what was once the city’s Roman hippodrome, repurposed during a period of intense mortality in the mid-6th to early 7th century. Through meticulous ancient DNA recovery techniques, the team sequenced genomes from eight individuals’ teeth, discovering nearly identical strains of Y. pestis, indicating a sudden and severe outbreak. This high genetic homogeneity reflects rapid disease transmission and devastating lethality, consistent with historical records describing the plague’s impact on population and infrastructure.

The study’s lead principal investigator, Dr. Rays H. Y. Jiang of USF’s College of Public Health, emphasized the significance of this finding, noting that centuries of historical documentation lacked biological corroboration until now. The genetic revelation not only validates written accounts but also inaugurates a new chapter in the genomic analysis of ancient pandemics. Dr. Jiang highlights that this research offers a rare glimpse into the pathogen’s behavior at the height of its destruction within a major urban center of the Byzantine Empire.

While prior investigations have recovered Y. pestis genomes from far-flung European villages, none had yet penetrated the heartlands of the Byzantine Empire or its earliest outbreak zones. This Jerash study bridges that geographic void and provides a critical spatial and temporal context for the bacterium’s ancient evolution. Researchers anticipate that this foundational work will catalyze further exploration of plague genomics within key trade and population centers of antiquity.

Co-investigator Dr. Greg O’Corry-Crowe of FAU’s Harbor Branch Oceanographic Institute and National Geographic Explorer remarked on the poignant contrast between the site’s original purpose and its later grim use. The Roman Hippodrome, a venue of public entertainment and urban pride, transformed into a mass grave under the strain of an overwhelming public health disaster. This shift offers important insights into how societies in antiquity responded to sudden outbreaks and the limits of urban resilience in the face of emerging infectious diseases.

Complementing these findings, a companion evolutionary study placed the discovered Y. pestis strains within a broader phylogenetic framework. By analyzing hundreds of ancient and modern Y. pestis genomes—including the newly sequenced Jerash strains—the researchers demonstrated that this bacterial lineage had circulated among human populations for millennia before the Justinian outbreak. Crucially, they found that later pandemics, such as the infamous Black Death in the 14th century and sporadic cases detected today, did not derive from a single common ancestor but emerged independently from persistent animal reservoirs.

This recurring pattern of plague emergence contrasts sharply with the recent SARS-CoV-2 pandemic, which originated from a singular zoonotic event followed by extensive human-to-human transmission. The multiplicity of independent spillovers identified for Y. pestis underscores the complexity of zoonotic disease ecology and the enduring interplay between pathogen reservoirs, environmental conditions, and human societal factors. These insights have profound implications for contemporary public health strategies aiming to mitigate similar risks.

The Jerash findings illuminate the persistent nature of plague as a public health threat despite its rarity in the modern era. Recent cases in the United States, including a fatal pneumonic plague infection in northern Arizona in 2025 and a milder case in California, underscore that Y. pestis remains an active zoonotic pathogen. The new genomic insights not only deepen our understanding of plague’s ancient history but also reinforce the need for continued vigilance against its contemporary resurgence.

Reflecting on the research experience, Dr. O’Corry-Crowe described the profound scientific and emotional impact of engaging with ancient human remains. Leveraging cutting-edge genomic technologies to resurrect the biological stories of individuals who perished centuries ago bridges the disciplines of archaeology, history, and molecular biology. He posited that this work offers a humbling perspective on the continuity of human suffering and resilience across epochs, and powerfully demonstrates the role of science in illuminating the past.

The team is actively expanding their research horizons to further investigate plague’s historical footprint. Among their next targets is Venice, Italy, specifically the Lazaretto Vecchio island, a prominent Black Death-era quarantine site and mass burial ground. Analysis of over 1,200 samples from this site, curated at USF, promises to shed light on how early public health interventions intersected with plague biology, urban vulnerability, and collective memory—advancing understanding of both ancient and modern pandemics.

Together, these findings mark a paradigm shift in pandemic research, revealing that outbreaks like the Plague of Justinian are not isolated calamities but part of complex, recurrent biological phenomena shaped by human mobility, ecological factors, and pathogen adaptation. The study highlights that controlling and understanding infectious diseases requires integrating genomic insights with historical and environmental contexts—a multidisciplinary approach critical to preparing for future pandemics.

As humanity confronts ongoing and emerging infectious threats, the legacy of plague stands as both a cautionary tale and a scientific beacon. The deep-time perspective afforded by this study affirms that pandemics are neither relics nor anomalies but enduring challenges necessitating vigilance, innovation, and global cooperation. The intersection of ancient DNA research and public health offers transformative potential to rewrite pathogen histories and bolster defenses against tomorrow’s outbreaks.

Subject of Research: People
Article Title: Genetic Evidence of Yersinia pestis from the First Pandemic
News Publication Date: August 27, 2025
Web References:

USF Health Faculty Page
MDPI Genes Journal Article
MDPI Pathogens Companion Study
Arizona Pneumonic Plague Case
California Plague Infection

References:

Journal: Genes
Articles led by USF and FAU teams published July 31, 2025

Image Credits: Greg O’Corry FAU

Keywords: Pathogens, Infectious disease transmission, Epidemiology, Disease outbreaks, Diseases and disorders, Health and medicine

Tags: ancient pandemics researchByzantine Empire pandemic historydirect evidence in ancient diseasesgenomic evidence of Yersinia pestishistorical epidemiology of plagueimpact of pandemics on societyJerash Jordan archaeological findingsmass grave excavation in Jordanorigins of the world’s first pandemicPlague of Justinianskeletal remains DNA analysisUSF FAU collaborative study