Discovery could help combat future pandemics.

What made the 1918 flu pandemic, also know as the "Spanish Flu", so deadly? Researchers may have finally answered that question, having found a group of three genes that let the virus invade the lungs and cause pneumonia.

Resarchers mixed samples of the 1918 strain of influenza with modern seasonal flu viruses to find the three genes, and published their results Tuesday in Proceedings of the National Academy of Sciences. They said that their study may help in the development of new flu drugs, and could also point to mutations that might turn ordinary flu into a dangerous pandemic strain.

Flu typically causes upper respiratory infection that affects the nose and throat, and systemic illness which causes fever, muscle aches, and weakness. However some people become seriously ill and eventually develop pneumonia. Bacteria sometimes causes the pneumonia, while other times the flu causes it directly.

During pandemics, such as the 1918 one, a new and more dangerous flu strain emerges. The 1918 pandemic caused 50 million deaths worldwide, and is considered to be the most devasting outbreak of infectious disease in human history. Health officials in recent years have been warning us that we are due for another flu pandemic of similar proportions.

The 1918 flu killed 2.5 percent of victims, versus the 1 percent killed during most annual flu epidemics. Autopsies of the victims showed that many had died of severe pneumonia.

Yoshihiro Kawaoka of the University of Wisconsin, along with colleagues at the Universities of Kobe and Tokyo in Japan wanted to know why the 1918 flu caused severe pneumonia. So they set out on the painstaking process of substituting single genes from the 1918 virus into modern flu viruses, and tested them out on ferrets, which develop the flu in much the same way as humans. One after another, they acted like the average flu, infecting just the upper respiratory tract. However, they found a complex of three genes helped make the virus live and reproduce deep in the lungs.

The genes - known as PA, PB1, and PB2 - coupled with a 1918 version of the nucleoprotein gene, made modern season flu kill the ferrets in a similar fashion as the original 1918 strain.