Century-Old Lungs May Push Origin of Measles Back 1,500 Years

The viral infection may have made its first hop into humans when large cities arose

Measles lung
Formalin-fixed lung collected in 1912 in Berlin from a 2-year-old girl who died of measles-related pneumonia Düx et al.

Nowadays, it’s hard not to have measles on the mind. Spurred in part by successful anti-vaccination campaigns, global cases of this viral infection reached their highest point in more than a decade during the first six months of 2019. In 2018, outbreaks killed more than 140,000 people worldwide.

But the scourge of measles isn’t just a problem of the present. This deadly disease has been plaguing human populations for centuries—perhaps even millennia. In a paper published last week on the preprint server bioRxiv, a team of researchers suggests the measles virus may have first tangoed with human immune systems as early as 345 B.C., or 1,500 years earlier than previously estimated. Though the findings have yet to be published in a peer-reviewed journal, they could push the origins of measles further back than ever before, reports Kai Kupferschmidt for Science magazine.

Prior investigations of measles’ evolutionary roots have been stymied by a lack of genetic data. Building such family trees means rewinding the clock—a process that typically requires multiple viral genomes, each isolated from different points in time, to estimate when separate lineages first split apart.

In 2010, a team of Japanese researchers tried their hand at this process with a handful of genomes from the measles virus, as well as some from its cattle-infecting cousin, the now-eradicated rinderpest virus. The group concluded that the former may have emerged in people around the 11th or 12th century A.D., perhaps after branching off from an ancestor that only infected non-human animals. Per Inverse’s Emma Betuel, this result seemed roughly in line with analyses of historical accounts, which tentatively pinpoint the virus’ start in humans to around 1000 A.D.

But only three of the measles genomes known to science predate 1990, leaving the oldest branches of the virus’ family tree sorely lacking. So, when Sebastien Calvignac-Spencer, an evolutionary biologist at the Robert Koch Institute, stumbled upon a set of 108-year-old measles-infected lungs in the basement of Berlin’s Museum of Medical History, he and his colleagues rushed to unravel the genetic material encoded within.

The lungs’ original owner was a 2-year-old girl who died of measles-related pneumonia in June 1912. After the tissues were fixed in formalin, they spent more than a century in obscurity. Thanks to careful preservation, however, the viral RNA found inside was still intact enough to yield a genome more than 100 years later. Paired with other genetic sequences, including a new set isolated from a virus dating to 1960, the data reconfigures the measles family tree. The virus’ hop into humans, the team’s analysis suggests, could have occurred as early as the fourth century B.C.

This date is just an estimate, and more samples and genetic sequences will be necessary to confirm such an ancient origin, says Monica Green, a historian of infectious diseases at Arizona State University who wasn’t involved in the study, to Kupferschmidt.

Still, the team’s new timeline happens to coincide with an important juncture in human history: the rise of large cities, home to populations of 250,000 or more. These swollen urban hubs, the researchers say, are about the minimum size a fast-spreading virus would need to sustain itself. Had measles tried to spread throughout smaller, more isolated groups, it probably wouldn’t have left enough survivors who were still susceptible to infection, thereby rapidly blipping back out of existence.

That’s just a theory for now. But if measles did indeed have an early arrival, its presence will likely be detectable in other medical artifacts from antiquity. The new study’s findings suggest those samples may yet be found and analyzed, Mike Worobey, an evolutionary biologist at the University of Arizona who also wasn’t involved in the study, tells Kupferschmidt.

Worobey adds, “Just being able to get the measles virus out of these old, wet specimens, … that sets the stage for all sorts of exciting work.”