(continued) How? Donis says that, although the equine and canine influenza strains are at least 96 percent genetically homologous, the canine virus appears to carry 8 to 10 amino acid changes in its hemagglutinin—an important surface protein on influenza particles that is critical for determining host specificity. Changes in other proteins, still under study, may also promote the virus's interaction with its new canine host. CDC scientists, in collaboration with scientists at the University of Florida and University of Kentucky, plan to continue comparing recent equine and canine influenza isolates—as well as to survey equine samples that are older. "We have equine influenza virus isolates, taken every year, back to 1963," Donis says. "So we can look at all of them and ask, 'Which mutations at what time enabled H3N8 to cross the species barrier into dogs?'" That may be the top question among scientists, but for pet owners another concern looms. If the flu can jump from horses to dogs, why not from dogs to people? The historical record provides some assurance, as well as uncertainty. "H3N8 has been in horses for more than 40 years," Donis notes. "In all this time, there has not been a single documented case of human infection. On the other hand, dogs have been living next to horses for the same period of time, and they didn't catch the equine flu virus until now. The reality is, we just don't know."

Influenza researchers are known to disagree on the finer points of avian flu, including just how great a threat it may pose to human beings. But the scientists are virtually unanimous on one point: Should this flu cause a pandemic, the world is not prepared for it. "The science is way ahead of the political will to solve these problems," says Robert G. Webster of St. Jude Children's Research Hospital in Memphis.

At a September influenza briefing on Capitol Hill sponsored by HHMI and the Center for Strategic and International Studies, Webster and several other researchers highlighted the importance of stockpiling influenza drugs, modernizing vaccine production, and planning for a worldwide disaster.

For many, it was a familiar refrain. "Ten years ago, I attended an influenza-pandemic preparedness meeting with some of the same people in this room," says Dominick Iacuzio, medical director at the pharmaceutical company HoffmanÐLa Roche, at the briefing. "Here we are again a decade later, still talking about being prepared."

Along the way, the scientists have actually made significant progress—in science. Hoffman-La Roche has released the antiviral drug Tamiflu (oseltamivir phosphate), designed to alleviate flu symptoms if taken early in the illness. Webster has probed the molecular biology and epidemiology of the H5N1 avian flu strain. Briefing participant Peter Palese of Mount Sinai School of Medicine and collaborators have reconstituted the 1918 flu strain to reveal its molecular secrets. And attendee Robert A. Lamb, an HHMI investigator at Northwestern University, has discovered the function of important elements of the replicating influenza virus. Other scientists have made similarly impressive gains.

Yet science can only go so far. "At the end of the day, public policy and government planning will make the difference," says Lamb. "European countries and Australia have done a much better job than the United States at stockpiling Tamiflu, for instance. In the U.S., all the available drugs would probably go to Congress and specific primary-care providers. What would happen if 20 percent, or 5 percent, or even 1 percent of Americans got sick?"

In one revealing moment at the September briefing, when an audience member pointedly asked the panel of scientists how the United States would cope with an influenza pandemic, they replied that the U.S. Department of Homeland Security (DHS) would ultimately be responsible for coordinating the day-to-day management of the crisis. To slow the flu virus's spread, they suggested, DHS might close schools and offices, shut down public transportation, and basically send the country home.

Weeks after the briefing, Webster reflected on this scenario and felt a lot less sanguine. Americans have since lambasted the federal government, including DHS, for its uneven response to the devastating Hurricane Katrina on the Gulf Coast. "There are so many indicators that a pandemic is brewing," says Webster. "We really can't be caught short. As in New Orleans, our levees have got to be built higher."

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