The Spanish Flu of 1918

Why flu remains a threat

Flu, it turns out, is a constantly moving target. The immune system recognises proteins or antigens on the surface of invading viruses or bacteria as foreign. It then mounts an attack on anything that carries similar antigens. Once infected by a particular virus, the immune system is able to respond to a second attack so rapidly that the disease never takes hold. This is the basis of immunity. Measles is a classic example of a viral infection from which we gain lifelong immunity after initial exposure.

But when it comes to immunity the flu virus has a trick up its sleeve. In a process known as antigenic drift, it constantly undergoes minor genetic changes that alter the constitution of its surface antigens. Every small change makes the virus less familiar to the human immune system and reduces the degree of immunity. This is why we can succumb to flu over and over again. And it explains why one year's flu vaccine doesn't stop you getting flu the following year, although it may help you to see off the infection quicker.

Every so often something even more dramatic happens to the flu virus (only to influenza A). The surface antigens undergo a major transformation that makes the virus a complete immunological stranger to the human immune system. Antigenic shift, as its known, is thought to happen when human viral strains incorporate genes from animal viral strains or when bird or animal viruses acquire the genes to invade human populations and transmit amongst human populations.

There are a large number of flu viruses that primarily infect birds. Most of these normally find it difficult to hop directly from bird to human, although this does happen occasionally and with disastrous results. The current outbreak of bird flu strain H5N1 is exceptional in this very ability, but it does require close contact between bird and human and hasn't yet evolved the ability to spread rapidly from human to human.

Domestic pigs, however, can be more readily infected both by bird flu strains and by human flu strains. Virologists believe that pigs might act as a kind of viral mixing bowl between the bird strain and the human strain, leading to an antigenic shift in the virus. Such antigenic shifts are possibly the key to creating highly infectious killer strains that could be the source of future flu pandemics.

Later pandemics in 1957 and 1968, nothing like as severe as that of 1918, have been shown to consist of strains that originated from a combined bird and human form. These two pandemics killed about three million people between them.

So, what did happen in 1918? John Oxford and his team found pathology reports from an army camp in Etaples, northern France, that have given him vital clues about the origin of the pandemic. Etaples was a huge army camp of 100,000 soldiers, almost the size of a city. The well and wounded moved through the camp daily. There is evidence that soldiers bought live geese, chickens and ducks from the local French markets. Crucially, there were lots of opportunities for a flu virus to move from bird to soldier. Since there were piggeries installed at Etaples, these animals could have been intermediaries, although recent genetic analysis of the 1918 virus shows it to be largely of avian origin.

Indeed, in the winter of 1916/1917, Etaples pathologists describe a disease-like flu that ended in heliotrope cyanosis and death. John Oxford believes the weight of evidence points toward Etaples as a hotbed for viral evolution that produced the 1918 strain of flu.

Another pandemic?

From studies on the 1918 pandemic and on living flu viruses, virologists believe that three factors are likely to increase the risk of creating a monster flu strain. They are: lots of people in close contact with live birds and possibly domestic pigs too.

South East Asia has often been cited as a potential epicentre for future pandemics because it has all three factors. Worryingly, the H5N1 flu virus is alive and well in the bird populations and has now spread to the eastern reaches of Europe – the time bomb is ticking away. Furthermore, warns John Oxford:

The World Health Organisation takes this warning seriously. In 1947 they set up an influenza programme – an information network that operates an early warning system for the emergence of new flu variants around the world. But one major problem in curbing the next pandemic will be that existing vaccines may not confer any protection against a virus that is radically different to any known strain. At the moment, it takes about six to eight months to make a new vaccine.

Huge progress has been made in understanding the flu virus itself, but by its very nature it is a difficult nut to crack. John Oxford leaves us with a warning: 'If we had another influenza pandemic, and we will have another influenza pandemic, I think it will make the HIV outbreak almost look like a picnic.'

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