Scientists have discovered the crucial changes to the avian flu virus that enabled it to cause the greatest infectious epidemic in history when it killed more than 20 million people worldwide in 1918.
Subtle alterations to the shape of a protein molecule of the 1918 virus allowed it to move from birds to humans where it quickly spread to infect an estimated one billion people, the scientists found.
The discovery will help scientists understand how the current avian flu outbreak in the Far East could change to result in a more infectious virus that would threaten to cause a global epidemic.
Using genetic information from samples of the 1918 virus recovered from frozen corpses buried in the Arctic tundra and preserved tissue samples kept in a hospital, the scientists reconstructed the viral protein that caused a strain of bird flu to infect human cells.
The protein - called haemagglutinin - sticks out like a series of spikes from the virus and enables it to lock on to the outer membrane of a human cell where it gains entry to cause an infection.
The 1918 influenza epidemic killed more people than the First World War yet the reasons remain a medical mystery essentially because the cause of flu was not known until scientists in Britain isolated the virus in 1933.
Today it is well established that new and deadly strains of flu can appear when bird flu infects humans and undergoes a change that allows it to spread. There are 15 known strains of avian flu but only three have become adapted to humans in the past century, causing the flu pandemics of 1918, 1957 and 1968, said Sir John Skehel, director of the National Institute for Medical Research in north London.
The latest outbreak of avian flu in South-east Asia has also resulted in bird-to-human transmission but has not yet become adapted for human-to-human transmission.
Sir John said: "This [study] is important because of the knowledge it brings about how these viruses, which originate in birds can jump to humans. This allows us to track and monitor the changes in the virus for public health purposes, even though it does not allow us to predict or prevent future forms of flu."
Two teams of researchers, one led by Sir John and another by Professor Ian Wilson of the Scripps Research Institute in San Diego, California, analysed the structure of the haemagglutinin protein that they had artificially synthesised from its gene.
The haemagglutinin gene of the 1918 virus was pieced together from samples from the body of an Inuit woman buried in the Alaskan tundra and preserved samples from US soldiers in the First World War.
An analysis of the protein's structure, published today in the journal Science, reveals that it had a particular shape which enabled it to attach easily to a protein on the surface of human cells.
"This tells us more about the transmission of infections from birds to humans. This explains how the 1918 virus spreads, it does not tell us why it was so pathogenic - why it was so deadly," Sir John said.
Previous studies show that the current virus infecting birds in the Far East is more like the human virus that caused the 1968 pandemic of "Hong Kong" flu. But it is possible there is another strain of avian flu that has a similar haemagglutinin protein to the 1918 virus, Sir John said.
A team led by Professor John Oxford of Queen Mary's School of Medicine in London is seeking permission to exhume the body of a woman who died of flu in 1918. Her remains were interred in a lead-lined coffin in Twickenham and they may be sufficiently well preserved for scientists to recover the virus intact.Reuse content