Genes shed light on 1918 pandemic

Medical sleuths probing a cold case involving one of the deadliest killers in history, the 1918 flu, reported Monday that they have edged closer to understanding what it takes to turn ordinary bird flu virus into a mass murderer.

The question carries more than scientific significance, with new versions of flu viruses turning up all the time. One of them, H5N1, has sickened millions of birds and killed nearly 400 people in more than a dozen countries worldwide since 2003, according to the World Health Organization.

“The big question is, ‘What does H5N1 need to spread globally?’ We don’t know anything about that,” says Terrence Tumpey of the Centers for Disease Control and Prevention, who pioneered the research and took part in two new studies. “We don’t even know what seasonal flu needs to spread.”

Answering such questions will help us recognize the next virus capable of causing a global pandemic, says James Paulson, a molecular biologist at the Scripps Research Institute in La Jolla, Calif., who wasn’t involved in the new studies. “There’s a new worldwide effort to survey (influenza) viruses in birds,” Paulson says, “but the tools we have are limited. We don’t know enough to assess what it takes to make a pandemic virus. What made the 1918 virus so special that it could enter the human population and, within a few years, kill 50 million people?”

Two years ago, Tumpey led a team of researchers who resurrected the 1918 virus using genes found in a victim. By studying the virus’s 10 genes, one by one, he says, researchers are uncovering clues to the traits that turned the virus into a monster capable of killing so many millions worldwide.

In one study, led by Ram Sasisekharan of the Massachusetts Institute of Technology, Tumpey and other researchers provide a more detailed picture of how two mutations allowed the virus to nest in cells in the upper respiratory tract.

The study, in Monday’s Proceedings of the National Academy of Sciences, found that the mutations enabled the virus to fix itself firmly to umbrella-shaped receptors in the respiratory tract. A natural variant of the 1918 virus, called NY18, did not have the same docking power or spread as readily in animal tests, Sasisekharan reported.

In the same journal, CDC’s Claudia Pappas and a team of researchers that also included Tumpey identified three genes that appear to be key to the 1918 virus’s virulence.

The researchers swapped multiple genes from the reconstructed virus with genes in seasonal strains of flu. They found three that appeared to boost flu’s ability to multiply in human airway cells and in mice.

Armed with such information, Paulson says, researchers will be able to study a virus taken from someone in, say, Indonesia, and see whether it can explode worldwide.

“So far that hasn’t happened,” he says. “That we can be grateful for.”