THE FLU pandemic that was first noted in 1918 was probably the worst catastrophe of the 20th century, if not of any century. The virus that caused it infected 500m people, more than a quarter of all those on Earth, and killed between 50m and 100m. By 1921, when the pandemic finally receded, it had reduced humanity by between 2.5% and 5%. In comparison, the first world war killed roughly 17m people, and the second around 60m people. Why was the 1918 flu so lethal?
It is a conundrum that scientists have deliberated over for a century, because the 1918 flu is an anomaly in the annals of flu pandemics too. There have been an estimated 15 of these in the past 500 years, but the numbers of sick and dead were not collected systematically until the late 19th century. Of the five flu pandemics that have been recorded since 1889, none besides the 1918 episode killed more than 2m people. In an average flu pandemic, 0.1% of those who fall sick go on to die, essentially of severe respiratory distress. In 1918, that number was 5-10%.
There are two broad schools of thought about what made 1918 exceptional. The first, to which several lines of evidence point, is that the virus was inherently potent. The genome of the 1918 flu virus was sequenced in 2005, after a preserved specimen was extracted from victims buried in Alaskan graves. It was then brought back to life. Using this, Aartjan te Velthuis, a virologist at the University of Cambridge, and colleagues have shown this year that, in the imperfect process of copying its genetic material or RNA, the 1918 flu virus—like the dangerous H5N1 avian-flu virus that is circulating in birds and can also infect humans—produces significantly more RNA fragments, or mini RNAs, than mild seasonal flu viruses. These mini RNAs bind to a human receptor known as RIG-I that triggers an immune response. The more mini RNAs, the stronger that response, and the more marked the resulting inflammation. Both the 1918 virus and H5N1 are known to produce massively inflamed lungs. Indeed there is debate as to whether it was the virus itself or the immune response it provoked that caused so many deaths in 1918.
The second approach considers factors extrinsic to the virus, such as the state of the world into which it erupted. According to Paul Ewald, an evolutionary biologist at the University of Louisville in Kentucky, for example, it is no coincidence that the most lethal flu pandemic on record coincided with a world war. In evolutionary terms, the optimal strategy for a virus transmitted directly between people, such as the flu, is to moderate its virulence, thereby keeping its host alive long enough to infect as many new hosts as possible. The war may have interfered with that process, though. On the Western Front, life in the trenches effectively immobilised large numbers of young men for days and weeks on end. In those circumstances, Dr Ewald argues, the pressure on the virus to reduce its virulence was relieved. The two schools of thought are by no means mutually exclusive. One lesson that can usefully be learned from 1918 would be that sometimes the worst consequences of war are unforeseen, and might come in the form of lethal, globe-encompassing disease.