Preliminary evidence suggests that swine flu may prove relatively mild, though scientists warn against drawing firm conclusions from on-the-fly early research.

Wired.com has learned that Lawrence Livermore National Laboratory computer scientists Jonathan Allen and Tom Slezak did not find similarities between swine flu and historical strains that spread widely, with catastrophic effect.

Their findings are based on just one complete sample and several fragmentary samples of swine flu, but fit with two other early analyses.

Taken together, all these findings fit the notion that more Mexicans are infected than was originally thought, that severe cases represent a fraction of the outbreak, and that mortality rates are lower than originally feared.

Researchers with the Great Britain's National Institute for Medical Research say swine flu's proteins suggest that it infects the upper rather than lower respiratory tract, reducing the damage it causes.

And two UK scientists have extrapolated a rough date for swine flu's emergence, and calculated the rate at which it appears to spread and mutate.

"If the calculations are correct," said Slezak, "it's indeed supportive of the other data that seems to agree that this is not going to be a catastrophic outbreak."

Allen and Slezak studied amino acid markers — subtle variations in the molecular composition of swine flu genes — found in a complete swine flu genome from a person infected in California, as well as several incomplete genomes from other samples.

Little more than a week ago, the pair published a paper in the journal BMC Microbiology describing the general patterns of amino acid markers in past flu strains that became either highly lethal and contagious, or comparatively benign.

The samples appear to fall into the "comparatively benign" category, though the researchers stress that it's only a preliminary finding, and that their BMC Microbiology findings have yet to be tested with a brand-new flu strain.

"This particular outbreak is going to be yet another data point to test," said Slezak. "If the hypothesis about the predictive value of these markers is correct, then we would hope that this won't be an especially severe outbreak."

Appearing to support their hopes are the findings of the National Institute for Medical Research. As reported Friday by the BBC, they found that swine flu's H1 gene — the virus is technically known as A(H1N1) — resembles the H1 gene of strains that reach their victims' upper respiratory tracts, but not their lungs. When flu enters the lungs, chemical fallout from a body's immune response can cause severe damage.

Another gene in the virus, known as NS1, belongs to a family of genes that seem to modulate immune response. The swine flu version resembles other NS1 variants that trigger a mild reaction.

Those researchers stressed the early nature of their findings, but they fit with Slezak and Allen's results. "The markers and observations appear consistent with respect to our initial observation that the genetic makeup is not remarkably similar to past pandemic variants," said Allen.

One more piece of the swine flu puzzle comes from the laboratories of University of Edinburgh viral geneticist Andrew Rambaut and epidemiologist Nicholas Grassly of Imperial College London. By studying subtle changes in the genetic makeup of swine flu samples and correlating them with the date of infection, Rambaut reverse-engineered an approximate starting date for the outbreak.

The date is extremely broad, falling between September of 2008 to the first documented swine flu case in March. "It is far too early to tell," said Rambaut. "I don't think we can say anything useful yet." But if the middle range of Rambaut's estimates hold, then Grassly calculates that the virus may not be spreading rapidly

But all this is still not certain. Asked whether a visitor to Mexico several months ago might have carried an early, less-virulent version of the virus to the outside world, while the Mexican version evolved in a more dangerous direction, Columbia University epidemiologist Ian Lipkin answered, "Absolutely."

Lipkin, a member of the World Health Organization's surveillance network who is now studying the outbreak in New York City, expounded on other possible reasons for flu's seemingly disparate effects inside and outside Mexico.

"The possible explanations are myriad. One is that a vaccine used in the past may have induced partial immunity. Or there may be differences in susceptibility, in everything ranging from genetics to environment to nutrition," he said.

Time will tell if the researchers' glimpses of swine flu resemble the entire picture. But even if predictions of global catastrophe prove unfounded, the flu may not pass quietly.

"I don't think this is going to hit us hard in the northern hemisphere," said Lipkin, noting that influenza spreads less easily in the summer, and vaccines should be ready by the time winter arrives. "But the southern hemisphere is going into the winter right now. They're at the greatest risk."**

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Image: CDC

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