Thread by @kakape

Some fascinating new data on another deadly pandemic:
Researchers have sequenced a full and two partial genomes of the 1918 flu from lung tissue in a museum collection in Berlin.

Story here, thread to come:
sciencemag.org/news/2021/05/h…

First of all:
This data comes from a preprint posted on @biorxivpreprint, so all the usual caveats about research that has not been peer-reviewed apply.
biorxiv.org/content/10.110…

@biorxivpreprint What we already knew:
There is very little genomic data on 1918 flu. Basically two full genomes from the US (one from a woman buried in permafrost in Alaska, one from a soldier who died in Camp Upton, NY) and a few dozen short fragments.

@biorxivpreprint Just for comparison: There have been far more than a million genomes of #SARSCoV2 sequenced in the current pandemic.
(Of course, influenza viruses weren’t even discovered in 1918 and so researchers are stuck trying to look back and sequence very old samples.)

@biorxivpreprint So what does the new study add:
The researchers looked at 13 lung specimens dated between 1900 and 1931 from two collections, at the Berlin Museum of Medical History and at the Natural History Museum in Vienna.
They got lucky with three samples, all from 1918.

@biorxivpreprint One sample came from a woman who died in 1918 in Munich (exact date unfortunately not known). Her lung sample was later transferred to the Berlin collection.
The researchers managed to sequence the entire genome. This is the first full 1918 flu genome from outside the US.

@biorxivpreprint Two samples came from young soldiers - one 17, one 18 years old - that died on the same day, 27th June 1918, in Berlin.
The researchers managed to sequence close to 90% of one and close to 60% of the other. These are the most complete sequences yet from the milder first wave.

@biorxivpreprint Obviously, given how few genomes of 1918 flu are available, any conclusions from comparing these have to be taken with a grain of salt.
Still, there are some tantalising clues here.
Let me spell out just two:

@biorxivpreprint 1. The previously reported flu sequences carry two mutations in the gene for the nucleoprotein that help the virus avoid our innate immunity: D16 and P283.
But the two Berlin sequences from the first wave carry the more bird-like versions (G16 and L283).

@biorxivpreprint As Sébastien Calvignac-Spencer, who led the work at @Leendertz_Lab told me, the virus might have adapted to humans this way: “It could be a sign that the virus was evolving to better avoid the human immune response in the first months of the pandemic."

@biorxivpreprint @Leendertz_Lab 2. The researchers assembled the entire polymerase complex from the Munich sequence and tested its activity in the lab. It was about half as active as the one from the Alaska sequence, suggesting that some of these genetic differences could have mattered in the pandemic.

@biorxivpreprint @Leendertz_Lab But the more important, broader point here is that these century-old RNA viruses can be sequenced much more easily now. It’s still not easy, Calvignac-Spencer told me. "But it’s not the kind of impossible work that we once thought it was.”

@biorxivpreprint @Leendertz_Lab So more genomes will likely be added in coming years as more and more researchers are able to do this work and that should give researchers much more data to investigate hypotheses about the 1918 flu.
It shows - once again - the value of museums and pathology archives.

@biorxivpreprint @Leendertz_Lab As @angie_rasmussen told me: "This paper elegantly shows that pathology archives may be a treasure trove of genetic information that could inform preparedness and prevention efforts, and we should think about how to best utilize these untapped resources for this purpose."