1918 Swine Flu outbreak

'Mother of pandemics'

But, during the last century, the virus has shown a deadly ability to change beyond recognition.

In 1918, an influenza pandemic started that became a global disaster - eventually killing more people than the Great War.

Estimates of the death toll from the 1918 outbreak of Spanish flu range from 20 million to 40 million. Some historians argue it could have been as high as 100 million.

"There was a mild wave in the spring, but the very serious, lethal wave was in the autumn to the winter," says Professor Markel. "Then a third wave in January to April 1919, and a fourth wave in the winter of 1920."

This tendency for "waves" of infection and re-infection makes the virus yet more unpredictable.


New vaccines for circulating strains are now designed every year
At the time the medical consensus was that the disease was caused not by a virus, but by a bacterium called Haemophilus influenzae.

So some countries, including the US and UK, distributed vaccinations against the wrong disease-causing agent.

"Another problem was that the authorities stuck their heads in the sand," says Mr Honigsbaum.

"Their priority was the war and they didn't have the resources to deal with the health crisis.

"There's an argument that if they'd been more proactive, and diverted doctors and nurses from the front to civilian needs, they could have saved more lives."

Dr Morens refers to the 1918 H1N1 strain as "the mother of all pandemics".

"In the category of Influenza A, which is the category of virus that has caused all human epidemics and pandemics, every virus circulated since 1918 has been a descendent of this virus in one way or another," he says.

"Descendants of the 1918 pandemic are still infecting human beings, but they have mutated again and again and again to be able to survive."

Hybrids and mutants

The 1918 influenza pandemic gripped a vulnerable, unprepared human population, but its ability to "reassort" - or exchange its genes with other viruses - was what made it "dangerously novel".

We had two lineages of the disease, both of which have persisted

David Morens
National Institute of Allergy and Infectious Diseases
"Every species has its own flu - when those species live together, and they can transmit their flu to different species, the virus itself changes its structure," says Professor Markel.

Since our immune systems recognise and respond mainly to the H and N part of the molecule, scientists suspect that pandemics arise when a strain emerges with a big change in the structure of one of these proteins.

But how exactly the virus adapts to enable it to attach to receptors on the cells of a different species, is an "unanswerable" question, says Dr Morens.

"With only four pandemics in over 100 years, our sample size is too small to say, but it seems that a new H [on the surface of the virus] has been the major factor," says Dr Morens.

"We don't know where the 1918 virus came from, but the evidence is that it was a new virus.

"At the same time that it infected humans, it also infected pigs. And at that point, we began to have two lineages of that disease - the human virus, and the pig virus, which persisted too," he adds.

The progeny of the 1918 influenza strain evolved and mutated as they were transmitted from one host to another.

And on two further occasions, these strains incorporated completely new genes and spread globally once again.

Controlled outbreak

"That's what happened in 1957 and 1968 - a hybrid formed of the 1918 virus with genes that were never part of it before," says Dr Morens.

In the case of the 1957 Asian flu outbreak, a human H2N2 virus combined with the genes of a strain found in wild ducks.

The pandemic killed an estimated one million people worldwide.

An outbreak of H3N2 Hong Kong flu in 1968, when avian and human virus genes combined once again, claimed another million lives.

In both cases, the impact was minimised by health authorities, who identified the virus, and made vaccines available.

"Now, every year, around summer time, a group of flu experts get together and see what strains are circulating so they can design an appropriate vaccine," says Dr Markel.

And in the last few years, principally because of the global concern about avian flu, anti-viral drugs that target influenza, such as Tamiflu, have been introduced.


The emergence of a virus that crosses a species barrier is extremely rare
But Professor Markel points out that, despite having reached new levels of medical preparation, "we live in a world of emerging infectious diseases".

"We have learned to take avian flu very seriously, and we have learned to take the animal kingdom very seriously," he says.

But in the rare event that a virus does develop that is able to cross the species barrier, he points out that the close proximity of domestic farm animals to humans provides an opportunity for human infection.

"Human beings travel farther and faster than ever before. All of this means that we are set up for a potential epidemic or pandemic," concludes Professor Markel.

"We learn more every time, but the story of flu pandemics is still very much a story in progress."