Scientists have worked out how the virus which caused the world's worst flu epidemic infected man.
The structure of a protein from the virus
They believe the virus, which claimed the lives of up to 50m people around the world, jumped from birds to humans.
The breakthrough, published in Science, should help doctors identify which future bird viruses pose a threat to man at an earlier stage.
But the National Institute for Medical Research team warns viruses cannot be stopped from crossing between species.
They also say their work is unlikely to aid the current fight against avian flu in the Far East as knowing the structure of a virus is not enough to block its progress.
The key first stage of infection is for the flu virus to attach itself to the cells in which it will breed.
MAJOR FLU OUTBREAKS
Spanish flu - 1918
Asian flu - 1957
Hong Kong flu - 1968
It does this by using spike-like molecules called Hemagglutinins (HA) that bind to particular receptors on the surface of cells in the body.
Human and bird virus HAs interact with different cell receptors and therefore bird viruses do not usually infect humans.
However, the NIMR team has studied the HA of the 1918 virus in close detail, and found that only minor changes in its structure were required for it to start to bind with human cells as well as bird cells.
This gave it the ability to pass from birds to humans, and then between humans - with devastating results.
The researchers examined samples of the 1918 virus using a technique called X-ray crystallography. This enabled them to determine the three-dimensional structure of its HA.
It seems part of the reason that the 1918 virus wreaked such devastation was because the changes required to pose a threat to humans were so small - smaller than those which made similar species-jumping viruses deadly in 1957 and 1968.
Lead researcher Sir John Skehel said the findings would enable scientists to track and monitor the changes in flu viruses.
However, scientists would not be able to predict the form future versions of the virus would take or prevent their formation, he said.
Sir John told BBC News Online: "This research should help improve surveillance.
"If we find that the structure of a bird virus resembles that of the structure of the 1918 virus that we have determined, then we will know that it potentially poses a threat to man, and it will have to be kept under more active surveillance than usual.
"However, our research will not have an immediate impact on the situation currently unfolding in the Far East with the chicken flu known as H5, since, from our previous work, we know that the 1918 and the H5 Hemagglutinins are quite different."
Huge death toll
The 1918 "Spanish" flu pandemic is estimated to have infected up to one billion people - half the world's population at the time.
The virus killed more people than any other single outbreak of disease, surpassing even the Black Death of the Middle Ages.
Although it probably originated in the Far East, it was dubbed "Spanish" flu because the press in Spain - not being involved in the Great War - were the first to report extensively on its impact.
The virus caused three waves of disease. The second of these, between September and December 1918, resulting in the heaviest loss of life.
It is thought that the virus may have played a role in ending the Great War as soldiers were too sick to fight, and by that stage more men on both sides died of flu than were killed by weapons.
Although most people who were infected with the virus recovered within a week following bed rest, some died within 24 hours of infection.