Lung Samples From 1918 Show a Pandemic Virus Mutating

Hundred-year-old lung tissue is incredibly hard to find. Sébastien Calvignac-Spencer, a virologist at the Robert Koch Institute, in Berlin, came across the samples in this newest study in a stroke of luck. A couple of years ago, he decided to investigate the collections of the Berlin Museum of Medical History of the Charité. He wasn’t looking for anything in particular, but he soon stumbled upon several lung specimens from 1918, a year he of course recognized as a notable one for respiratory disease. Despite the flu pandemic’s notoriety, the virus that caused it is still poorly understood. “I thought, Well, okay, so it’s right here in front of you. Why don’t you give it a try?” he told me. Why not try to sequence influenza from these lungs? (This work is not dangerous: The chemically preserved lung specimens do not contain intact or infectious virus; sequencing picks up just fragments of the virus’s genetic material.)

Calvignac-Spencer and his colleagues ultimately tested 13 lung specimens and found evidence of flu in three. One was from a 17-year-old girl who died in Munich sometime in 1918. The two others were from teenage soldiers who both died in Berlin on June 27, 1918. This work is described in a new preprint, which has not yet been peer-reviewed.

The team was able to recover a complete flu-virus genome from the 17-year-old girl’s lung tissue—only the third ever found. The two other full 1918 flu genomes both came from the United States, from the lungs of a woman buried in Alaska and from a paraffin-wax-embedded lung sample of a soldier who died in New York. With another genome in hand, the researchers moved to investigate how they differed. Several changes showed up in the flu’s genome-replication machinery, a potential evolutionary hot spot because better replication means a more successful virus. The team then copied just the replication machinery of the 17-year-old’s virus—not the entire virus—into cells and found it was only half as active as that of the flu virus found in Alaska.

The obvious caveats should apply here: tiny sample size, the limits of extrapolating from test tube to human body. The exact date of the girl’s death in 1918 is also unknown, but this finding hints at the possibility that the virus’s behavior did change during the pandemic. Scientists have long speculated about why the 1918 pandemic’s second wave was deadlier than the first. Patterns of human behavior and seasonality could explain some of the difference—but the virus itself might have changed too. “And this starts to put some meat on the bone” of that hypothesis, Andrew Mehle, an influenza researcher at the University of Wisconsin at Madison, who was not involved in the study, told me.

The lungs of the two young soldiers in Berlin provide another clue. The teenagers’ June 1918 deaths were squarely in the pandemic’s first wave. These two samples yielded only partial genomes, but the team was able to reconstruct enough to home in on changes in nucleoprotein, one of the proteins that make up the virus’s replication machinery. Nucleoproteins act like scaffolds for the virus’s gene segments, which wind around the protein like a spiral staircase. They are also extremely distinctive, which can be a weakness: The human immune system is very good at recognizing and sabotaging them.

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