H7N9 more likely to transmit among humans

Spanish flu research

An electron micrograph showing recreated 1918 influenza virions.

Centers for Disease Control and Prevention as Dr. Terrence Tumpey examines a reconstructed version of the 1918 flu.

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.(Harvard Open Collections) 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.^[73][74]

Others have disagreed,^[75] and more recent research has suggested the strain may have originated in a nonhuman, mammalian species.^[76] An estimated date for its appearance in mammalian hosts has been put at the period 1882–1913.^[77] 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 1918 flu strain (a subtype of avian strain H1N1) was a collaboration among the Armed Forces Institute of Pathology, 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 a female flu victim buried in the Alaskan permafrost and samples preserved from American soldiers.^[78]

On 18 January 2007, Kobasa et al. reported that monkeys (Macaca fascicularis) infected with the recreated strain exhibited classic symptoms of the 1918 pandemic, and died from a cytokine storm^[79]—an overreaction of the immune system. This may explain why the 1918 flu had its surprising effect on younger, healthier people, as a person with a stronger immune system would potentially have a stronger overreaction.^[80]

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 to have helped preserve the virus.^[81] However, the coffin was found to be split because of the weight of soil over it, and the cadaver was badly decomposed. Nonetheless, samples of lung and brain tissue were taken through the split, with the coffin remaining in situ in the grave during this process.^[82]

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 1918 flu samples to the ability of the flu virus to invade the lungs and cause pneumonia. The combination triggered similar symptoms in animal testing.^[83]

In June 2010, a team at the Mount Sinai School of Medicine reported the 2009 flu pandemic vaccine provided some cross-protection against the 1918 flu pandemic strain.^[84]

One of the few things known for certain about the influenza in 1918 and for some years after was that it was, out of the laboratory, exclusively a disease of human beings.^[85]