Study Finds Pig Role in 1918 Pandemic's Evolution

LAURAN NEERGAARD,
AP Medical Writer

WASHINGTON—History's deadliest flu pandemic, in 1918, may not have made a sudden jump from birds to people after all.

New research says the pig played a big role as an influenza mixing bowl — a gene probe with lessons for tracking today's swine flu outbreak.

The genetic ancestor hunt shows pieces of the 1918 killer virus were quietly circulating in people and pigs up to 15 years before the pandemic erupted, researchers reported Monday.

That argues for better surveillance of percolating flu strains, not just in the long term but right now. Scientists worry that the current influenza pandemic — the never-before-seen swine flu strain now crossing the globe — could become worse as it runs into other types of flu.

"We need to be vigilant for any genetic mixing of strains currently circulating in humans," lead researcher Dr. Gavin J. D. Smith of the University of Hong Kong said in an e-mail interview.

Catch two different flu viruses at once and a new one can emerge, something scientists call reassortment. Birds are the ultimate origin of influenza viruses, but because pigs can catch both bird and human flu strains, they've long been recognized as a species mixing vessel. The study, in Monday's Proceedings of the National Academy of Sciences, provides the first evidence that the 1918 pandemic — like the two that followed it, in 1957 and 1968 — evolved from a series of those reassortments, not a sudden jump.

The new swine flu — a part-pig, part-human, part-bird virus that's in the same influenza family, called H1N1 — also evolved gradually.

"The one thing that we do know about this 2009 H1N1 is that it likes to mate," said study co-author Dr. Robert Webster, a well-known influenza specialist from St. Jude Children's Research Hospital in Memphis.

His biggest fear isn't that the novel swine flu will mix with some regular winter flu as both types start circulating when cold weather hits — but that it might hang around long enough in places like China or Indonesia to mate with an extremely lethal bird flu that sometimes jumps from poultry to people.

"Whoa, let's hope not," said Webster, who just became an adviser to the Obama administration's flu team. "But we can't rule it out."

World health authorities are closely watching the Southern Hemisphere, where flu season just began, to see how dangerous the new swine flu proves. U.S. authorities estimate that a million people here have become ill since spring, with more than 200 deaths. While most patients recover easily, young people seem particularly vulnerable. And a related study released Monday by the journal Nature warns that the swine flu spreads through the entire respiratory system, especially the lungs, more easily than its seasonal counterparts.

Amid the uncertainty, the U.S. government is racing to begin a mass vaccination campaign in mid-October, targeting school-age children first. But the World Health Organization warned Monday that the novel virus is proving more difficult to grow into vaccine than anticipated, potentially delaying those efforts.

Scientists have long tracked influenza by its changeable coating, proteins on its surface — the "H'' and "N'' that provide its family name — that trigger the immune system to mount an attack.

Smith's team provides a more in-depth look at the evolution of all eight gene segments that make up influenza viruses. That offers virologists more clues to understand what changes are most important on the path to virulence, potential red flags that they can monitor with the novel swine flu.

"It's a very exciting paper because it tells us we may be able to predict how things are going to go in the future," said Dr. Shanta Zimmer of the University of Pittsburgh School of Medicine, who recently co-authored a similar historical look at swine flu evolution. "We should try to understand more about what makes influenza severe or not severe."

Another surprise: When history books tell us that the 1918 pandemic started out mild and returned with a bang, maybe the reason is two separate viruses. Smith's study found evidence that a milder sister strain of H1N1 circulated at the same time.

"This work suggests that the generation of pandemic strains and the adaptation to humans could be much more involved that what was previously thought," said Dr. Raul Rabadan of Columbia University.