Researchers may have found the cause of the mysterious and devastating 1918 flu pandemic.

The research team believes the key to understanding the pandemic, which killed 50 million people, is in childhood exposure to the virus, a University of Arizona news release reported.

"Ever since the great flu pandemic of 1918, it has been a mystery where that virus came from and why it was so severe, and in particular, why it killed young adults in the prime of life," Arizona researcher Michael Worobey,  a professor in the UA Department of Ecology and Evolutionary Biology, said in the news release. "It has been a huge question what the ingredients for that calamity were, and whether we should expect the same thing to happen tomorrow, or whether there was something special about that situation."

The new research suggests which strains of the virus people were exposed to in childhood could predict their level of susceptibility when exposed to other strains down the road.

The team took an "unprecedentedly accurate molecular clock approach," to reconstruct the H1N1 influenza A virus (IAV) that caused the pandemic.

Their findings suggested the virus originated just before the pandemic when new genetic material was acquired from a past bird flu virus that had been circulating for up to 15 years before.

"It sounds like a modest little detail, but it may be the missing piece of the puzzle," Worobey said. "Once you have that clue, many other lines of evidence that have been around since 1918 fall into place."

Babies and elderly people are usually most susceptible to flu fatalities, but the 1918 pandemic killed mostly individuals between the ages of 20 and 40. The researchers believe this occurred because people in this age group were exposed to a "putative H3N8 virus" that circulated in their childhood, the news release reported. Those born before and after this time would have been protected due to exposure to "N1 and/or H1-related antigens."

"Imagine a soccer ball studded with lollipops," Worobey said. "The candy part of the lollipop is the globular part of the HA protein, and that is by far the most potent part of the flu virus against which our immune system can make antibodies. If antibodies cover all the lollipop heads, the virus can't even infect you."

"But a person with an antibody arsenal directed against the H3 protein would not have fared well when faced with flu viruses studded with H1 protein," Worobey said, "And we believe that that mismatch may have resulted in the heightened mortality in the age group that happened to be in their late 20s during the 1918 pandemic."

The findings could help researchers better prevent in influenza deaths in the future.

"What seems to be the decisive factor is prior immunity," Worobey said. "Our study takes a variety of observations that have been difficult to explain and reconciles and places them into a logical chain able to explain many patterns of influenza mortality over the last 200 years. What we need to do now is to attempt to validate these hypotheses and determine the exact mechanisms involved, then apply that knowledge directly to better prevent people from dying from seasonal flu and future pandemic strains."