In a first-of-its-kind study, scientists from the Queensland Spatial Biology Centre (QSBC) will use spatial biology to delve into lung tissue samples from victims of the 1918 Spanish flu pandemic. Spearheaded by Associate Professor Kirsty Short, Dr. Arutha Kulasinghe, and Professor John Fraser, this study, funded by Wesley Research Institute, will enable the researchers to explore the molecular mechanisms of the host immune response to viral infection.
Associate Professor Kirsty Short of The University of Queensland
The team aims to shed light on why children and young adults suffered disproportionately severe outcomes during the historic outbreak. “This research will provide a better understanding of the structure, function and interactions of cells affected by the Spanish Flu virus that caused disproportionately high mortality rates among otherwise healthy children and young adults,” said Associate Professor Short. And looking towards the future, these insights will be invaluable in informing how we tackle current endemic viruses like the flu as well as future major outbreaks.
Precious Samples Unearthed from Historic Pandemic
The 1918 Spanish flu pandemic, one of the deadliest in history, had a peculiar characteristic: it was disproportionately lethal to healthy young adults and children. But even 100 years later, scientists still do not know what made this demographic more susceptible. To address this question, PhD student, Lauren Steele tracked down a precious lung tissue sample, preserved in formaldehyde and paraffin, from a European museum where it lay virtually forgotten for over a century. This unique tissue sample, from an 18-year-old German soldier who died of Spanish flu, will be the focus of a spatial phenotyping study to understand the immune response to the H1N1 influenza A virus that causes Spanish flu.
Patients receiving treatment during the 1918 Spanish flu, which killed an estimated 50 million people globally
However, working with a 100+-year-old sample is a challenging task. Only recently, scientists believed a sample dating back to 1919 would be unusable for this type of molecular profiling. Typically, paraffin-embedded tissues are stored for about ten years before being discarded. As Dr. Arutha Kulasinghe said, “It should not be possible to get signal off 100-year-old tissues. Most scientists think what we are doing here is not conceivable. Running this experiment live, we’re seeing what a disease that is 100 years old did to people’s bodies for the first time. It is incredible.”
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Hear from scientists at the Queensland Spatial Biology Centre (QSBC) located at the Wesley Research Institute in Australia share their motivations and expectations for this unique scientific study.
Modern Technology to Reveal Secrets Locked in 100-Year-Old Sample
The QSBC team will use their Akoya PhenoCycler-Fusion 2.0 to perform spatial phenotyping on the preserved lung tissue samples. The PhenoCycler-Fusion 2.0 employs molecular barcoding chemistry that enables ultrahigh-plex analysis of up to 100+ markers on a tissue sample, allowing for deep insights. This chemistry is also unique in that it safeguards tissue integrity with gentle, isothermal processes during staining and imaging, which is critical for such a precious sample. This advanced spatial biology technoloy will allow the Fraser Institute scientists to explore tissue composition, cell interactions, and disease-associated changes in the Spanish flu victim tissue samples.
Early Spatial Phenotyping Data are Promising
Despite the potential technical hurdles of working with such an old tissue sample, the team of cross-disciplinary experts’ initial findings are promising. In their first glimpses of the young German soldier’s lung tissue, they noted extensive infiltration of macrophages, which signals that this patient experienced a hyperinflammatory immune response within his lungs shortly before dying.
A Leap Forward in Pandemic Preparedness
Leveraging these historical Spanish flu samples will provide valuable knowledge to inform future pandemic preparedness. By understanding why younger individuals were more severely affected in 1918, researchers hope to develop vaccines and treatments tailored to protect these populations in upcoming health crises. This could mark a paradigm shift in how we approach pandemic response, focusing on the unique vulnerabilities of different age groups. Ultimately, the insights gained in this study are expected to guide the development of more effective vaccines and therapies for these vulnerable age groups in future pandemics.
Stay tuned for findings from this work to be published in 2025.
- Read more about this project from the Wesley Research Institute and learn about other exciting projects taking place at the QSBC
- See how the PhenoCycler-Fusion 2.0 solution is helping provide insights into complex biological systems and gain a better understanding of cellular microenvironments
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