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One hundred years ago, the world was just beginning to recover from the bloodiest conflict in humanity’s history. Up to 19 million people died during the four years of World War I, including eight million civilians. And yet, as the guns fell silent and people began to pick up the pieces of their war-torn lives, the world was being struck by a humanitarian disaster that would dwarf even the horrors of a World War.

“Spanish ‘flu”, or more accurately “Influenza H1N1 1918”, is the most deadly infectious disease pandemic in history. The first patients began to appear in January 1918 and by the spring it was clear that this was a global healthcare disaster. However, with the war still in full flow, government censors suppressed reporting in order to maintain morale. Consequently, most European countries appeared superficially to be unaffected and only those, such as Spain, that were neutral reported the full impact of the pandemic – leading to the unfortunate and inaccurate label of “Spanish ‘flu”.

By the time the pandemic was over, at the end of 1920, every corner of the globe had been affected, one in three people worldwide had been infected and between 50 and 100 million people had died – up to 6% of the entire human population. At its peak, Spanish ‘flu was killing one million people per week – the population of modern-day Birmingham.

The reasons for the profound lethality of the 1918 pandemic remain enigmatic. Work several years ago to reconstitute this particular strain of ‘flu and test it within high-containment laboratory conditions suggested that Spanish ‘flu provokes a particularly potent ‘cytokine storm’ - in essence, an overreaction of the human immune system, leading to organ damage and respiratory failure. This finding goes some way to explaining the otherwise inexplicable observation that Spanish ‘flu was more likely to kill young, healthy adults than babies or the very old. However, this increased biological virulence was probably dramatically augmented by the social impact of the end of the war. Large numbers of people moving around the world and often living in overcrowded, unsanitary conditions created the perfect conditions for an airborne virus to spread rapidly.

With a century of hindsight, what lessons can we learn from the Spanish ‘flu pandemic? A moratorium on recreating highly virulent ‘flu strains, put in place due to fears of a laboratory escape, has recently lifted, meaning that we may soon have a better understanding of what made this particular strain so virulent. In addition, our understanding of influenza more broadly is clearly vastly better than it was in 1918 and we have access to a range of antivirals that, in some cases, are effective at reducing symptoms.

On the other hand, we now live in a world which is more densely populated and interconnected than ever before. Today, international flights mean that a highly virulent strain of influenza can transmit between continents within hours and rapidly find itself in a megacity with a network of millions of susceptible people living within coughing distance of each other. Whilst a near-instantaneous global communication system ought to make simple public health interventions such as handwashing and tissue use easier to implement, 21st century society is far less likely to accept effective, but draconian, interventions such as compulsory quarantine.

Perhaps the most promising route to heading off a pandemic influenza disaster is to try and minimise the chance of highly-virulent novel strains of the virus entering the human population in the first place. We now know that most virulent ‘flu strains jump into the human population from bird or pig reservoirs, and that ‘recombinant’ strains which contain novel mixtures of viral genes are particularly dangerous. Thus, reducing the number of situations in which humans, pigs and birds - particularly domestic poultry - live at high density in close proximity to one another is one way to delay, if not prevent entirely, the evolution of new influenza strains. However, in a world with two billion pigs, seven billion humans and 20 billion chickens, this is certainly easier said than done. In the meantime, avoiding a 21st century ‘Spanish ‘flu’ pandemic is probably going to rely on sensible tissue use, good hand washing - and a substantial amount of luck.

Professor Robin May, Director of the Institute of Microbiology and Infection at the University of Birmingham