Scientists have traced the genetic lineage of the new H1N1 swine flu to a strain that emerged in 1998 in U.S. factory farms, where it spread and mutated at an alarming rate. Experts warned then that a pocket of the virus would someday evolve to infect humans, perhaps setting off a global pandemic.

The new findings challenge recent protests by pork industry leaders and U.S., Mexican and United Nations agriculture officials that industrial farms shouldn't be implicated in the new swine flu, which has killed up to 176 people and on Thursday was declared an imminent pandemic by the World Health Organization.

"Industrial farms are super-incubators for viruses," said Bob Martin, former executive director of the Pew Commission on Industrial Animal Farm Production, and a long-time critic of the so-called "contained animal feeding operations."

As Wired.com reported on Tuesday, geneticists studying the composition of viruses taken from swine flu victims described it as the product of a DNA swap between North American and Eurasian swine flu strains.

On Wednesday, Columbia University biomedical informaticist Raul Rabadan added new information on the virus' family history in a posting to ProMed, a public health mailing list. His description paralleled that of other researchers who had analyzed the new strains, but with an extra bit of detail. Six of the genes in swine flu looked to be descended from "H1N2 and H3N2 swine viruses isolated since 1998."

Experts contacted by Wired.com agreed with Rabadan's analysis. For researchers who track the evolution of influenza viruses, the news was chilling.

H3N2 — the letters denote specific gene variants that code for replication-enhancing enzymes — is the name of a hybrid first identified in North Carolina in 1998, the tail end of a decade which saw the state's hog production rise from two million to 10 million, even as the number of farms dropped. H3N2 originated in a relatively benign swine flu strain first identified in 1918, but had absorbed new genes from bird and human flus.

These new genes provided replication advantages that allowed the hybrid to permeate densely packed pig farms whose inhabitants were routinely shipped across the United States. That rapid replication rate also increased the chances of strains evolving in ways that allowed them to evade hog immune systems.

Within a year, exposures topped 90 percent in several heartland states. A retrospective news account in Science said that "after years of stability, the North American swine flu virus had jumped on an evolutionary fast track."

At the genetic level, the years that followed remain a mystery — hog flus are poorly monitored, compared to human influenza. But eventually an H3N2 spawn merged with a strain of Eurasian pig flu, producing the swine flu variant that's now infecting humans.

At an environmental level, the conditions which shaped H3N2 and H1N2 evolution, and increased the variants' chances of taking a human-contagious form, are well understood. High-density animal production facilities came to dominate the U.S. pork industry during the late 20th century, and have been adopted around the world. Inside them, pigs are packed so tightly that they cannot turn, and literally stand in their own waste.

Diseases travel rapidly through such immunologically stressed populations, and travel with the animals as they are shuttled throughout the United States between birth and slaughter. That provides ample opportunity for strains to mingle and recombine. An ever-escalating array of industry-developed vaccines confer short-term protection, but at the expense of provoking flu to evolve in unpredictable ways.

The Pew commission concluded that this system created an "increased chance for a strain to emerge that can infect and spread in humans." Scientists and public health experts have said the same thing for years, in even starker terms.

In 2003, the American Public Health Association called for a ban on contained animal feeding operations. One year later, St. Jude's Children's Hospital virologist Richard Webby, one of the original chroniclers of H3N2's emergence, called the U.S. swine population "an increasingly important reservoir of viruses with human pandemic potential." United States Department of Agriculture researcher Amy Vincent reportedly said that vaccine-driven evolution created a "potential for pandemic influenza emergence in North America."

Officials and the pork industry argued this week that a direct link hadn't been found to pigs, and that the new flu strain had yet to be found in farm animals or workers, both in the United States and at a giant hog factory near the outbreak's epicenter in La Gloria, Mexico. Owned by a subsidiary of Smithfield Foods, the largest U.S. pork producer and a notorious polluter, the factory processes one million hogs each year.

As of now, neither swine flu nor its close relatives have been found anywhere. But "that probably says more about the lack of sampling in pig flu than anything else," said Andrew Rambaut, a University of Edinburgh viral geneticist who has studied swine flu. "We don't sample nearly the complete diversity of pig flu around the world. Most outbreaks go unstudied."

On Thursday, Reuters called concern with "evil factory farms in Mexico" one of many "wild theories," on a par with a conspiracy between Al Qaeda and Mexican drug cartels. Indeed, the location may yet prove coincidental. But absence of evidence at the factory and elsewhere is not evidence of absence.

The new swine flu could have emerged in a myriad number of ways, passing between any number of birds and pigs and people, at locations across North America, during its evolutionary journey. It may well prove impossible to pinpoint exactly where it first emerged or became infectious to people. But most of its genes are almost certainly part of a North American industrial virus lineage long expected to produce pandemic variants like this one.

"We haven't found evidence of infected pigs," said Ian Lipkin, a Columbia University epidemiologist and member of the World Health Organization's surveillance network. "But even if we never find that smoking pig, we can surmise that this is probably where it came from."

The circumstances "are certainly enough to warrant asking questions," said Lipkin. "The question, then, is how deeply do you want to look to try to find the evidence?"

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Image: USDA

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