Scientists Decode 1918 Flu Virus Genome From Century-Old Tissue

Scientists have decoded the Swiss genome of the 1918 flu virus from a century-old specimen, revealing early adaptations for human infection.

Scientists from the Universities of Basel and Zurich have successfully decoded the genome of the influenza virus that caused the 1918–1920 pandemic in Switzerland, using a preserved specimen from the University of Zurich’s Medical Collection. Their analysis shows that the virus had already acquired crucial traits for infecting humans at the very beginning of what would become the most lethal influenza outbreak ever recorded.

The emergence of new viral epidemics continues to pose serious risks to global health. To better prepare for future outbreaks, it is essential to understand how viruses evolve and to study the patterns of past pandemics. The 1918–1920 influenza pandemic, often referred to as the Spanish flu, resulted in an estimated 20 to 100 million deaths around the world. However, scientists have had limited information about how the virus changed and adapted as the pandemic unfolded.

More than 100-year-old flu virus sequenced

Now, an international team of researchers, led by Verena Schünemann—a paleogeneticist and professor of archaeological science at the University of Basel (previously at the University of Zurich)—has reconstructed the first Swiss genome of the 1918 influenza virus.

For their study, the researchers used a more than 100-year-old virus taken from a formalin-fixed wet specimen sample in the Medical Collection of the Institute of Evolutionary Medicine at UZH. The virus came from an 18-year-old patient from Zurich who had died during the first wave of the pandemic in Switzerland and underwent autopsy in July 1918.

Three key adaptations in Swiss virus genome

“This is the first time we’ve had access to an influenza genome from the 1918–1920 pandemic in Switzerland. It opens up new insights into the dynamics of how the virus adapted in Europe at the start of the pandemic,” says last author Verena Schünemann. By comparing the Swiss genome with the few influenza virus genomes previously published from Germany and North America, the researchers were able to show that the Swiss strain already carried three key adaptations to humans that would persist in the virus population until the end of the pandemic.

Two of these mutations made the virus more resistant to an antiviral component in the human immune system – an important barrier against the transmissions of avian-like flu viruses from animals to humans. The third mutation concerned a protein in the virus’s membrane that improved its ability to bind to receptors in human cells, making the virus more resilient and more infectious.

New genome-sequencing method

Unlike adenoviruses, which cause common colds and are made up of stable DNA, influenza viruses carry their genetic information in the form of RNA, which degrades much faster.

“Ancient RNA is only preserved over long periods under very specific conditions. That’s why we developed a new method to improve our ability to recover ancient RNA fragments from such specimens,” says Christian Urban, the study’s first author from UZH. This new method can now be used to reconstruct further genomes of ancient RNA viruses and enables researchers to verify the authenticity of the recovered RNA fragments.

Invaluable archives

For their study, the researchers worked hand in hand with UZH’s Medical Collection and the Berlin Museum of Medical History of the Charité University Hospital. “Medical collections are an invaluable archive for reconstructing ancient RNA virus genomes. However, the potential of these specimens remains underused,” says Frank Rühli, co-author of the study and head of the Institute of Evolutionary Medicine at UZH.

The researchers believe the results of their study will prove particularly important when it comes to tackling future pandemics. “A better understanding of the dynamics of how viruses adapt to humans during a pandemic over a long period of time enables us to develop models for future pandemics,” Verena Schünemann says.

“Thanks to our interdisciplinary approach that combines historico-epidemiological and genetic transmission patterns, we can establish an evidence-based foundation for calculations,” adds Kaspar Staub, co-author from UZH. This will require further reconstructions of virus genomes as well as in-depth analyses that include longer intervals.

Reference: “An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe” by Christian Urban, Bram Vrancken, Livia V. Patrono, Ariane Düx, Mathilde Le Vu, Katarina L. Matthes, Nina Maria Burkhard-Koren, Navena Widulin, Thomas Schnalke, Sabina Carraro, Frank Rühli, Philippe Lemey, Kaspar Staub, Sébastien Calvignac-Spencer and Verena J. Schuenemann, 1 July 2025, BMC Biology.
DOI: 10.1186/s12915-025-02282-z

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