Scientists have shown that tiny changes to modern flu viruses could render them as deadly as the 1918 strain which killed millions.
Some experts believe a flu pandemic is overdue
A US team added two genes from a sample of the 1918 virus to a modern strain known to have no effect on mice.
Animals exposed to this composite were dying within days of symptoms similar to those found in human victims of the 1918 pandemic.
The research is published in the journal Nature.
The work of the US team, lead by Dr Yoshihiro Kawaoka of the University of Wisconsin, was carried out under the tightest security.
Experts focused on two genes thought to play a key role in the infection process.
One controls production of a spike-like molecule called haemagglutinin (HA), believed to be used by the flu virus to attach itself to the cells it is about to infect.
Previous research published earlier this year in the journal Science identified the HA gene as being the crucial element which made the 1918 virus so deadly - and the latest work appears to confirm this.
Post mortems on mice injected in the nose with the composite virus showed that it had rampaged through their lungs, producing inflammation and haemorrhaging.
The researchers stress the experiment is conclusive for lab mice, and not humans.
But they say that their work may lead to better ways to assess the potential danger of emerging flu viruses.
Writing in Nature, the researchers say: "Once the properties of the (1918) HA gene that gave rise to its lethal infectivity are better understood, it should be possible to
devise effective control measures and to improve global surveillance networks for influenza viruses that pose the greatest threat to humans as well as other animal species."
Scientists believe the 1918 virus leapt to humans by mutating from bird flu, possibly after passing through pigs, which are able to harbour both human and avian viruses and thus allow them to swap genes as the viruses reproduce.
For that reason, experts are deeply concerned that the avian flu that has broken out in poultry flocks in parts of south-east Asia may acquire genes that will make it highly infectious as well as lethal for humans.
Professor John Oxford, an expert in virology at Queen Mary College London, told BBC News Online the latest research underlined just what a threat all flu viruses potentially posed.
He said: "It is not a big difference at all between a virus that kills 15m people and one that does not kill anyone at all.
"The lesson is not to be complacent about anything to do with flu. Every flu virus must be carrying baggage that could potentially harm us, and we would be well advised not to ignore them."
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 World War I - 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 World War I 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.