The postwar killer
Spanish ﬂu ravaged a continent already devastated by World War I
More people succumbed to ﬂu in 1918–19 than died at enemy hands. An outbreak of ﬂu in 1918 is estimated to have infected perhaps one in ﬁve of the world’s population. In just one year it killed more than 40 million people.
Conditions at the end of World War I may have contributed to the spread of the virus and hence the scale of this pandemic. It became known as ‘Spanish ﬂu’ because of the attention given to it by the Spanish press, which was not censored as much as the papers in other countries.
The number of people the Spanish flu killed in just one year
Although ﬂu had always been a risk to infants, the elderly or weak, Spanish ﬂu was different: it also carried off healthy people in the prime of their lives.
Scientists have been able to recover isolates of this deadly strain from the preserved remains of an American serviceman and from a ﬂu victim exhumed from a frosty mass grave in Alaska. In 2005 sequences from these sources were used to reconstruct the 1918 virus.
The genetic sequences of these isolates suggest that the virus was of avian origin rather than a human variety. Although risky, researchers have recreated the 1918 virus and tested its effects on animals (oddly, ferrets are the best match for the human respiratory system). In macaques the virus triggers a massive immune response – a ‘cytokine storm’ – that rapidly destroys the lungs.
And they may have discovered how a bird virus came to kill so many humans. By making just two amino acid changes in the outer haemagglutinin protein, researchers created a virus that was still lethal to ferrets but which was not transmitted between them. The changes alter the type of sugar molecules to which the haemagglutinin binds. The fear is that these changes will happen in reverse in today’s avian ﬂu virus – turning it into a virus that can spread between people.
Unpicking the past
Comparisons between the 1918 virus genome and those of other pandemic and seasonal viruses are shedding new light on the Spanish flu pandemic – and may hold important lessons for today.
The origins of the 1918 virus have been debated, and its unusually severe effects on young adults have long puzzled scientists. Possible answers have come from a study examining how the virus genome evolved before and after the 1918 pandemic.
These results suggest that the virus emerged just before 1918, when a human H1 virus acquired N1 and other genes from an avian virus. The pandemic virus rapidly spread to pigs, but was displaced in humans in around 1922 by reassortment and the introduction of a different form of H1.
The pig viruses went on to seed further pandemics later in the century, which can be seen as descendants of the 1918 pandemic. Indeed, it could be argued that all the pandemics of the past 100 years are part of a ‘super-pandemic’ (and similar pandemic eras may have existed at other points in human history).
Why so deadly?
And what of the 1918 virus’s unusual pathogenicity? Several features of the virus have been suggested to contribute to its virulence, but looking just at the virus may not be enough. Young adults may have been particularly vulnerable because, unlike other age groups, when young, they were exposed to an H3N8 virus (which circulated between 1889 and 1900) rather than an H1 virus. So they never developed any protection against H1.
In the modern era this could explain why the seasonal H3N2 influenza virus, which used not to have a major effect on older people, now causes more severe disease: in the 1960s older people would have been exposed to the H3 virus, while elderly populations today grew up with H1N1. Immunisation strategies mimicking this beneficial effect of early exposure could therefore have a significant impact on seasonal flu in the future.
Analysis of the 1918 virus has thus taught us much – not just about one of the most devastating episodes in human medical history, but also about how we might prepare for the next.Lead image:
Navy Medicine/Flickr CC BY
- 1918 influenza: the mother of all pandemics
- Wikipedia: 1918 flu pandemic
- Characterization of the reconstructed 1918 Spanish influenza pandemic virus (2005)
- Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus (2007)
- Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus (2006)
- Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus (2014)
- Pandemic influenza: certain uncertainties (2011)
- Reconstruction of the 1918 influenza virus: unexpected rewards from the past (2012)