Controversies in - and potentials for - interdisciplinary plague research

Human plague was reactivated in Central Asia in the early 14th century, spread into Europe with the Black Death in 1346/47 CE and continued there as the Second Pandemic until the early 19th century. The Third Pandemic, genetically linked to the Second, emerged in the late 19th century and persisted until 1950, after which plague disappeared from Europe but remains endemic in several areas regions globally. Despite major advances in genetics, ecology, and history, key controversies persist regarding the origins of Yersinia pestis reservoirs, the establishment and persistence of plague in Europe, and the varying dynamics and outcomes of successive outbreaks. These debates, echoing similar uncertainties in modern zoonotic diseases such as Ebola or SARS-CoV-2, highlight the need for genuinely interdisciplinary collaboration. Here, we review the major controversies in plague research and propose integrative approaches that align biological, environmental, and socio-historical data to resolve them. Doing so not only deepens understanding of plague’s complex dynamics but also informs the study of other emerging infectious diseases.