On May 29, 2025, scientists at the Institut Pasteur and McMaster University announced they have discovered that the evolution of a gene in the bacterium that causes bubonic plague, Yersinia pestis, may have prolonged the duration of two major pandemics.

They have demonstrated that modifying the copy number of a specific virulence gene increases the length of infection in affected individuals. It is thought that this genetic change may prompt longer periods of contagiousness in less densely populated environments, in which the time of transmission from one individual to another is inevitably longer.

This genetic variation has been observed in strains of each of the two major plague pandemics, hundreds of years before they eventually faded out. The study was published in the journal Science.

There are three major plague pandemics documented in human history. The first broke out in the Mediterranean basin in the 6th century. The second emerged in the 14th century, reemerging on several occasions in Europe over a period of more than 500 years. The first wave of this second pandemic, known as the “Black Death,” remains the deadliest event ever recorded in human history, killing an estimated 30 to 50 per cent of the European population between 1347 and 1352.

The third plague pandemic occurred in Asia in 1850. This pandemic spread to and across every continent, and still persists today in “endemic” regions, encompassing countries like Uganda and the Democratic Republic of Congo, as well as the United States and Mongolia.

In mice models of bubonic plague, the scientists found that depletion in the copy number of the pla gene leads to a 20 per cent decrease in mortality and an increase in the length of infection in affected individuals, meaning the infected rodents lived longer before they died.

The scientists propose that rats infected with these bacteria could spread infection farther in an environment with a reduced mammal population density. The high mortality rate among rodents at the start of pandemic waves drives a decrease in host proximity. “Diminished virulence may give the bacillus a selective advantage within a reduced population density,” explains Javier Pizarro-Cerdá. The pandemics eventually faded out, probably due to the reduced virulence of these strains.