Research

The origin of the Spanish flu pandemic, and the relationship between the near-simultaneous outbreaks in humans and swine, have been controversial. One hypothesis is that the virus strain originated at Fort Riley, Kansas, in viruses in poultry and swine which the fort bred for food; the soldiers were then sent from Fort Riley around the world, where they spread the disease. Similarities between a reconstruction of the virus and avian viruses, combined with the human pandemic preceding the first reports of influenza in swine, led researchers to conclude the influenza virus jumped directly from birds to humans, and swine caught the disease from humans.

Others have disagreed, and more recent research has suggested the strain may have originated in a nonhuman, mammalian species. An estimated date for its appearance in mammalian hosts has been put at the period 1882–1913. This ancestor virus diverged about 1913–1915 into two clades (or biological groups), which gave rise to the classical swine and human H1N1 influenza lineages. The last common ancestor of human strains dates to between February 1917 and April 1918. Because pigs are more readily infected with avian influenza viruses than are humans, they were suggested as the original recipients of the virus, passing the virus to humans sometime between 1913 and 1918.

An effort to recreate the Spanish flu strain (a subtype of avian strain H1N1) was a collaboration among the Armed Forces Institute of Pathology, the USDA ARS Southeast Poultry Research Laboratory, and Mount Sinai School of Medicine in New York City. The effort resulted in the announcement (on 5 October 2005) that the group had successfully determined the virus's genetic sequence, using historic tissue samples recovered by pathologist Johan Hultin from an Inuit female flu victim buried in the Alaskan permafrost and samples preserved from American soldiers Roscoe Vaughan and James Downs.

On 18 January 2007, Kobasa et al. (2007) reported that monkeys (Macaca fascicularis) infected with the recreated flu strain exhibited classic symptoms of the 1918 pandemic, and died from cytokine storms – an overreaction of the immune system. This may explain why the Spanish flu had its surprising effect on younger, healthier people, as a person with a stronger immune system would potentially have a stronger overreaction.

On 16 September 2008, the body of British politician and diplomat Sir Mark Sykes was exhumed to study the RNA of the flu virus in efforts to understand the genetic structure of modern H5N1 bird flu. Sykes had been buried in 1919 in a lead coffin which scientists hoped had helped preserve the virus. The coffin was found to be split and the cadaver badly decomposed; nonetheless, samples of lung and brain tissue were taken.

In December 2008, research by Yoshihiro Kawaoka of the University of Wisconsin linked the presence of three specific genes (termed PA, PB1, and PB2) and a nucleoprotein derived from Spanish flu samples to the ability of the flu virus to invade the lungs and cause pneumonia. The combination triggered similar symptoms in animal testing.

In June 2010, a team at the Mount Sinai School of Medicine reported the 2009 flu pandemic vaccine provided some cross-protection against the Spanish flu pandemic strain.

One of the few things known for certain about influenza in 1918 and for some years after was that it was, except in the laboratory, exclusively a disease of human beings.

In 2013, the AIR Worldwide Research and Modeling Group "characterized the historic 1918 pandemic and estimated the effects of a similar pandemic occurring today using the AIR Pandemic Flu Model". In the model, "a modern-day 'Spanish flu' event would result in additional life insurance losses of between US$15.3–27.8 billion in the United States alone", with 188,000–337,000 deaths in the United States.

In 2018, Michael Worobey, an evolutionary biology professor at the University of Arizona who is examining the history of the 1918 pandemic, revealed that he obtained tissue slides created by William Rolland, a physician who reported on a respiratory illness likely to be the virus while a pathologist in the British military during World War One. Rolland had authored an article in the Lancet during 1917 about a respiratory illness outbreak beginning in 1916 in Étaples, France. Worobey traced recent references to that article to family members who had retained slides that Rolland had prepared during that time. Worobey extracted tissue from the slides to potentially reveal more about the origin of the pathogen.citation needed