Genetic Samples of 1918 Flu Viruses Recovered from 100-Year-Old Tissue Sample???

The Spanish flu pandemic, which ravaged the world from 1918 to 1919, resulted in an estimated death toll of around 50 million people.

Despite its immense impact, the causative agent remained elusive for nearly a century. Researchers didn’t even know that a virus was responsible for the disease until the causal agent was finally?isolated in a lab?in 1930.

Advancements in technology enabled scientists to gain more insights into this deadly virus. However, questions persisted about the pandemic's progression and the factors that drove changes in the virus over time.

The Breakthrough: Sequencing the Spanish Flu

Fast forward to the early 2000s, a group of scientists worked to unveil the cause of the virulence of the Spanish flu. They turned to FFPE blocks that contained lung tissue samples from individuals who succumbed to the flu in 1918.

Two of the cases analyzed were U.S. Army soldiers who died in September 1918, one in Camp Upton, New York, and the other in Fort Jackson, South Carolina.

The 1918 pandemic, a zoonotic disease thought to have jumped into people from?birds. 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. 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. These sequences shed light on how the virus may have become deadlier.

Most telling, though, was the whole genome. The 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 a 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, suggesting that the pandemic worsened after the virus adapted to its human hosts.

Significance and Future Possibilities

The significance of this achievement extends beyond solving the Spanish flu mystery.

Every few years, influenza epidemics boost the annual number of deaths past the average, causing 10–15,000 additional deaths. Occasionally, and unpredictably, influenza sweeps the world, infecting 20 percent to 40 percent of the population in a single year. In these pandemic years, the number of deaths can be dramatically above average. In 1957–58, a pandemic was estimated to cause 66,000 excess deaths in the United States. In 1918, the worst pandemic in recorded history was associated with approximately 675,000 total deaths in the United States and killed an estimated 40 million people worldwide.

Influenza A viruses constantly evolve by the mechanisms of antigenic drift and shift. Consequently, they should be considered emerging infectious disease agents, perhaps “continually” emerging pathogens. The importance of predicting the emergence of new circulating influenza virus strains for subsequent annual vaccine development cannot be overestimated. It underscored the immense potential of using preserved tissues to unravel historical medical enigmas. These blocks have since been employed to investigate other ancient diseases, shedding light on the evolution and epidemiology of pathogens from the past.

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If you want to know more about the wonders of tissue preservation, sign up for our upcoming webinar on 'Isolating high-quality DNA from FFPE samples'.??

We will explore the profound impact of formalin on long-term tissue preservation and the challenges it brings to extract nucleic acids.

For its solution, we will provide exclusive insights into the Cambrian gDNA FFPE extraction kit, which is built on magnetic nanoparticles, and shows high performance with?a yield >50 ng and purity between 1.8 - 2.0.??

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