Millions were killed by the virus

The lungs of infected monkeys were destroyed in just days as their immune systems went into overdrive after a Canadian laboratory rebuilt the virus.

The reason for the lethal nature of the 1918 flu was never fully understood.

But the experts behind this test say they have found a human gene which may help explain its unusual virulence.

This research provides an important piece in the puzzle of the 1918 virus

Darwyn Kobasa

Public Health Agency of Canada

They are hoping to help control any future pandemic and believe that the strain may hold clues that will help them.

Despite the large number of casualties at the time, doctors had no way to preserve tissue samples taken from infected patients, so researchers used an ingenious method to overcome this.

Frozen body

The preserved body of a flu victim buried in Arctic permafrost was exhumed, and they painstakingly extracted the genetic material needed to work out the structure of the H1N1 virus.

Then, in a maximum "biosafety" facility at Canada's National Microbiology Laboratory they reconstructed a fully functioning virus, and infected macaque monkeys to see what would happen.

Writing in the journal Nature, they reported that the results were startling. Symptoms appeared within 24 hours of exposure to the virus, and the subsequent destruction of lung tissue was so widespread that, had the monkeys not been killed a few days later, they would literally have drowned in their own blood.

The results match those seen when mice were infected in an earlier study and are very similar to those described in human patients at the time the virus was at its height.

Dangerous virus

Darwyn Kobasa, a research scientist with the Public Health Agency of Canada, and lead author of the research, defended the decision to recreate one of the most dangerous viruses in history.

He said: "This research provides an important piece in the puzzle of the 1918 virus, helping us to better understand influenza viruses and their potential to cause pandemics."

However, it is not the virus that is directly causing the damage to the lungs - it is the body's own response to infection.

Immune system proteins that can damage infected tissue were found at much higher levels following H1N1 infection compared with other viral infections.

Analysis at the University of Wisconsin at Madison (UW) revealed that a key component of the immune system, a gene called RIG-1 appeared to be involved.

Levels of the protein produced by the gene were lower in tissue infected with the 1918 virus, suggesting it had a method of switching it off, causing immune defences to run wild.

Many influenza virologists remain nervous about creating and experimenting with a reconstructed 1918 Spanish flu virus

Dr Jim Robertson

National Institute of Biological Standards and Control

This ability to alter the body's immune response is shared with the most recent candidate for mutation into a pandemic strain, the H5N1 avian flu.

Experts are worried that if the virus changes so that it can infect humans easily, it could again be far more lethal than normal seasonal flu.

"What we see with the 1918 virus in infected monkeys is also what we see with H5N1 viruses," said Yoshihiro Kawaoka, who led the analysis at UW.

"Things may be happening at an early time point (in infection), but we may be able to step in and stop that reaction."

Preparing for pandemic

Dr Ronald Cutler, an infectious diseases researcher at the University of East London, said: "Knowing how that over stimulation takes place could lead to the development of new methods to treat these diseases so we are better prepared for any future pandemic."

Dr Jim Robertson from the UK's National Institute for Biological Standards and Control, said the decision to recreate the virus was justified.

"Many influenza virologists remain nervous about creating and experimenting with a reconstructed 1918 Spanish flu virus, an extremely dangerous virus which disappeared from the world long ago.

"However, it cannot be denied that the information that has been derived from this experiment is exciting and represents an important milestone in understanding the severity of these highly pathogenic types of influenza viruses."