The team discovered that the reason it was so deadly was because a group of three genes allows the virus to invade the lungs and cause pneumonia.
They discovered the three genes by mixing samples of the 1918 influenza strain with modern seasonal flu viruses and they believe their findings may help in the development of new flu drugs and also indicate mutations that might turn ordinary flu into a dangerous pandemic strain.
For their research virologist Dr. Yoshihiro Kawaoka of the University of Wisconsin and colleagues at the Universities of Kobe and Tokyo in Japan used ferrets, which develop flu in ways very similar to humans.
As a rule, flu causes an upper respiratory infection affecting the nose and throat, as well as so-called systemic illness causing fever, muscle aches and weakness but some people become seriously ill and develop pneumonia caused by bacteria or by the flu.
It is during pandemics that new and more dangerous flu strains emerge and the researchers say the 1918 influenza pandemic was the most devastating outbreak of infectious disease in human history causing about 50 million deaths worldwide.
Kawaoka's team say that pandemic killed 2.5% of victims, compared to less than 1% during most annual flu epidemics and autopsies revealed that many of the victims, often otherwise healthy young adults, died of severe pneumonia.
Kawaoka's team wanted to find out why the 1918 flu caused severe pneumonia so they carefully substituted single genes from the 1918 virus into modern flu viruses and they behave like common flu, infecting only the upper respiratory tract.
However the team found that a complex of three genes PA, PB1, and PB2 - along with a 1918 version of the nucleoprotein or NP gene, helped to make the virus live and reproduce deep in the lungs and enabled made modern seasonal flu to kill the ferrets in much the same way as the original 1918 flu did.
Experts agree that a pandemic of influenza will almost certainly strike again and while no one knows when or what strain it will be, the prime suspect is the H5N1 avian influenza virus currently doing the rounds in poultry in Asia, Europe and parts of Africa.
Though it rarely affects humans, it has already killed 247 of the 391 people infected since 2003 and just a few mutations could turn it into a pandemic strain that could kill millions globally within a few months.
While there are available four licensed drugs to fight flu, the viruses regularly mutate into resistant forms that evade antibiotics.
The research is published in the current issue of the Proceedings of the National Academy of Sciences and was funded by the Japanese Ministry of Education, Culture, Sports, Science and Technology and by grants-in-aid from the Ministry of Health, Labour and Welfare of Japan.
