“With viruses, we don’t have fossils,” says Calvignac-Spencer. But in recent years, scientists have started rummaging through old pathology collections and using computational models to trace the otherwise lost history of viruses. Calvignac-Spencer thought he might do the same for measles, which is why he got in touch with the Berlin Museum of Medical History at the Charité. The museum was eager to collaborate and to find new uses for its extensive pathology collection.
Pathology samples are usually preserved in formalin, a chemical solution that halts decay by stopping all biological processes but also “glues” RNA to other molecules. (Viruses can use RNA or DNA as their genetic code; measles is an RNA virus.) To extract just measles RNA, the team would have to break those links to other molecules. The easiest way is with heat. “You boil the sample,” explains Calvignac-Spencer. The team boiled the lung sample at 98 degrees Celsius for 15 minutes. With that, they were able to extract RNA from the measles virus and reconstruct its genome.
Read: Why is measles back?
To reconstruct an accurate history of measles, however, you need not one but many measles genomes, the older the better. So Calvignac-Spencer and his colleagues went searching for others. In a reference lab, they found another isolate from Czechoslovakia in 1960, which they also sequenced. They scoured the literature for the published genomes of 127 other more modern measles isolates. Finally, they compared all the measles genomes with those of its closest cousins: rinderpest, a since-eradicated virus that once devastated cattle herds, and peste des petits ruminants, a virus that still infects goats and sheep. Measles was probably an animal virus that spilled over into humans.
By modeling how these viruses would have evolved over time, the team concluded that measles and rinderpest likely diverged 2,400 years ago. Sometime after that—though this study cannot resolve exactly how long after—measles evolved to exclusively infect humans.
This divergence date would fit what many measles researchers have long suspected about the virus and the appearance of big, dense human cities. Measles is exceptionally contagious, but anyone who survives it becomes immune. In a small community, everyone will quickly catch measles and either die or develop immunity; the virus runs out of victims to infect. But in a large, dense city, where susceptible babies are being born all the time, measles can sustain its chain of transmission, says Ottar Bjornstad, an epidemiologist at Penn State. Around 2,300 years ago, cities in North Africa, India, China, and Europe began growing to hundreds of thousands of people—large enough, presumably, to begin sustaining measles. This may be the story of how measles came to infect humans.