IT MUST SEEM like the sky is falling -- that it's about to rain chaos and death as the dreaded H5N1 avian flu appears to close in.
Last spring, bird flu broke out in Cambodia, Thailand and Vietnam. It spread to western China, Siberia, Kazakhstan and Mongolia in the summer. How did it travel half a continent?
Though maps of the outbreaks show the flu following roads, railway lines and national borders, many flu experts insist that migratory birds spread the virus across Asia. Julie Gerberding, director of the Centers for Disease Control and Prevention, warned that some of the birds might fly to Alaska, then down into the United States, bringing the bird flu with them. That hasn't happened, but the virus appears to be in Europe. Last week, ducks and chickens were found dead in Romania, Turkey and Greece.
News reports make the threat even more ominous. In resurrecting the 1918 pandemic virus, the deadliest flu strain of all time, researchers recently learned that this strain was far deadlier than any other human virus -- it killed mice, while normal human flu won't even ruffle a mouse's fur. They also found out that all of its genes came, directly or indirectly, from birds. Unlike the pandemics of 1957 and 1968, the 1918 version didn't arise from a combination of bird and mammal genes. Instead, the bird genes evolved into a human virus that killed as many as 50 million people.
This means, say breathless news reports, that what happened in 1918 could happen again, this time with H5N1.
But Peter Palese doesn't think so. He is lab director at Mount Sinai Hospital in New York, where the technique that re-created the 1918 genes -- known as reverse genetic engineering -- was developed. He and associate Adolfo Garcia-Sastre contend that what the resurrected virus really shows is how supremely adapted it is -- how well its parts fit together, how perfectly it works. The sublime malignance of the 1918 virus doesn't lie in one part but rather in how the genes function together. Evolution shaped this virus to be a sleek, effective killing machine.
We don't know what bird the genes came from originally. It wasn't a domestic duck, chicken or goose, because their flu strains are quite different. According to Jeffery Taubenberger, the senior researcher at the Armed Forces Institute of Pathology, the 1918 flu originated in an unknown bird reservoir, one equally distant from American and Eurasian birds. "To me, it's from an unknown host, evolutionarily isolated from other birds," Taubenberger said last year.
But all wild-bird viruses are mild. They have to be: Sick birds don't fly far, and dead birds don't fly at all. Although H5N1, which evolved among domestic poultry in the crowded conditions of Asian farms and markets, has demonstrated the ability to kill wild birds in the hundreds, it cannot continue to be so deadly and still spread among them.
In nature, flu viruses in birds are intestinal diseases. Through feces, flu particles are deposited in water, where another duck or goose picks them up, gets infected and sheds the virus in turn. Wild-bird flu depends on mobile hosts to spread. If flu strains kill their hosts in the wild, the lethal versions will vanish. This is why evolution pushes wild-bird strains toward mildness.
To think that the 1918 flu started out as a harmless intestinal bird virus that jumped directly from its wild host into human beings and immediately turned into an explosive respiratory killer is to believe that hippos fly. Evolution doesn't work that way. The flu's genes came from birds, but it's what they did when they got into humans that matters.
Somehow, somewhere, the mysterious gene collection that made up the 1918 killer influenza acquired its adaptive and lethal abilities in people. Most influenza viruses are respiratory and require mobile human hosts, who become viral distribution machines. You might be miserable with the flu, but you're still able to walk around, shake hands, sneeze on your keyboard and talk to colleagues with a halo of virus around you.
But the 1918 pandemic strain was different. According to evolutionary biologist Paul W. Ewald of the University of Louisville, its lethality evolved in the trenches, the trucks, the trains and the hospitals of World War I. Infected soldiers were packed shoulder to shoulder with the healthy, and even the deadliest virus can jump from one host to another. The Western Front was a disease factory, and it manufactured the 1918 flu. The packed chicken farms of Asia are a close parallel. H5N1 evolved the same way as the 1918 flu did in the trenches.
We don't know what will happen to H5N1 as it moves through Europe. It is certain, though, that the longer it lives in wild birds, the more likely it will become mild, at least for its wild-bird hosts. This is what happened to the 1918 flu after soldiers abandoned the Western Front. In just over a year, the virus lost its virulence and wandered the planet as an ordinary flu.
The lesson here is that the flu virus, like all of life, is subject to evolution. Lethal diseases don't fall out of the sky. They evolve in the context of a host and that host's conditions of life. There is no sign, so far, that H5N1 is turning into a human disease -- effectively spreading from person to person. Even if it does, it needs a Western Front to become more than ordinary.