100-Year-Old Lungs Yield Genetic Samples of 1918 Flu Viruses

Influenza RNA sequences from three sets of lungs preserved in formalin since 1918 provide new insights into the deadly pandemic.

Christie Wilcox
May 18, 2021
ABOVE: Masked Red Cross workers in Saint Louis, Missouri, during the fall wave of the 1918 influenza A pandemic.
LIBRARY OF CONGRESS

Three teenagers—two soldiers and a civilian—were among the 50 million or more estimated casualties of the 1918 influenza A pandemic. However, unlike most people who were killed by the virus, the lungs of the three were saved, preserved in formalin for more than one hundred years. Now, according to a preprint uploaded to bioRxiv on May 14, these organs are providing genetic clues as to why the virus took so many lives, Science reports.
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The 1918 pandemic, a zoonotic disease thought to have jumped into people from birds, was one of the deadliest pandemics on record. Especially lethal were the second and third waves of cases, which occurred starting in the fall of that year. It’s likely that variants of the virus played a role in the differing damage caused by each wave. Unfortunately, obtaining viral RNA sequences from samples that old is technically fraught. In fact, until recently, extracting RNA from century-old specimens would have been considered “a fantasy,” Hendrik Poinar, an ancient DNA scientist at McMaster University who was not involved in the study, tells Science.

Even obtaining samples is hard, preprint coauthor Michael Worobey, an evolutionary biologist at the University of Arizona, tells Science. Still, the team was able to secure a total of 13 lung tissue samples from people who died between 1900 and 1931 from specimens that were being housed in the Berlin Museum of Medical History and the pathology collection of the Natural History Museum in Vienna; three of them, all from 1918, contained influenza RNA.

While the RNA was highly fragmented, the team was able to reconstruct between 60 and 90 percent of the genomes of the viruses that killed the two soldiers, and the entire genome of the virus that killed the civilian. The new sequences are all from the first wave of the pandemic, and when compared with the previously described strains from later on in the pandemic, they hint at how the virus may have become deadlier. For example, the two partial genomes from the soldiers contain sequences that are more “bird-like,” reports Science—a sign that early versions of the virus may have had more difficulty infecting people.

See “1918 Flu Spread Before Peak”

Most telling, though, was the whole genome. From it, researchers were able to recreate the virus’s polymerase complex, and put it head-to-head against the polymerase complex resurrected from a previously published virus strain sequenced from person who died in Alaska in November 1918. In cell cultures, the complex from the first wave virus constructed RNA at roughly half the efficiency of the virus from a later wave.

“The fact that you can test, in vitro, the effects of an ‘extinct’ strain has huge implications in understanding evolution of virulence and possible countermeasures should we encounter another flu epidemic,” Poinar tells Science.

“It’s absolutely fantastic work,” he adds. “The researchers have made reviving RNA viruses from archival material an achievable goal.”