The Race Against Avian Flu

In the calendar of natural calamities, flu season follows hurricane season, peaking in midwinter. Last week, with New Orleans still mostly uninhabitable, Washington was turning its attention to the threat posed by an exceptionally lethal strain of flu virus that could, in the worst case, kill as many people in a few months as AIDS has done in two decades. This time officials were resolved not to repeat the mistakes of Katrina, leaving the way open to make new mistakes. We now know better how to evacuate large cities--but how much good will that do in an emergency that calls for a quarantine instead?

At least no one could accuse the government of downplaying the threat: President Bush himself raised the possibility of using the military to contain a flu outbreak, while the Senate voted to spend $4 billion on preparations. Researchers have developed a promising vaccine that is now beginning large-scale production. But new fears arose last week when scientists announced they had reconstructed an actual living copy of the "Spanish flu" virus that killed 20 million to 50 million people in 1918. Apart from the implication that a terrorist could do the same thing, the disturbing news was that the culprit was essentially a bird virus which had undergone only "minimal changes to infect humans directly," according to microbiologist Terrence Tumpey of the Centers for Disease Control and Prevention. (More common, and less lethal, flu outbreaks are caused by germs that are a hybrid of mammalian and avian viruses.) As Tumpey points out, that is also a pretty accurate description of the H5N1 flu virus that has been circulating in Asia since 1997. (It is not related to the SARS outbreak of 2003.) In the last two years H5N1 has killed 140 million birds; it has infected just 116 people, mostly in Vietnam--but it was fatal to more than half of them. The critical difference from 1918 is that the newer virus is not ordinarily contagious between people. Almost everyone who has come down with it has caught it from a bird. So far.

Most researchers think our luck won't hold--that as the trillions of flu viruses at loose in the world replicate and mutate, it's only a matter of time before one evolves the ability to spread by way of a cough or a handshake. Then our fate will be decided in a race between the virus's inherent lethality and the tendency of all germs to evolve toward a less deadly form because their own spread depends on not killing the host--us--too quickly. Some researchers like our odds. In 1918, millions of soldiers and civilian refugees on the move in crammed trains and ships created an ideal situation for spreading flu, and there was nothing like today's techniques for surveillance and isolation of patients. "I actually have confidence about this," says Paul Ewald, a biologist at the University of Louisville. "It won't race around the world like a new 1918 virus."

We also have medical resources undreamed of in 1918. Last year molecular virologist Richard Webby of St. Jude Children's Research Hospital in Mem-phis, Tenn., announced he had "reverse engineered" a version of the H5N1 virus that could be the basis for a vaccine, keeping the parts that are recognized by the human immune system while disabling a critical disease-causing function. It took just "a few weeks," says Linda Lambert, who is coordinating the government's bird-flu-vaccine program. The resulting vaccine has been tested on 450 volunteers, and preliminary results are promising, at least for the highest doses tested; like many vaccines, it will probably have to be given in two shots, a month apart. On the assumption it will work, but also in part just to get a production line up and running, the government last month awarded a $100 million contract to Sanofi Pasteur of France, aiming for a stockpile of 20 million doses. The vaccine is tricky to manufacture, because it requires injecting virus into live chicken eggs; under a separate contract, the same company is researching a cell-based production system that could show results by the end of the decade.

The second line of defense against avian flu is antiviral drugs, in particular one called Tamiflu from the Swiss drugmaker Roche. Viruses replicate by commandeering a cell's genetic machinery to copy themselves; Tamiflu prevents the daughter viruses from escaping to infect new cells. It has shown good results against H5N1 in cell cultures and in mice, and it works against milder forms of the flu in humans, if they take it the first day or two after falling ill. But the real test will come only when and if a lot more people are infected with H5N1; one expert in infectious disease, Michael Osterholm of the University of Minnesota, admits that "we don't honestly know" if Tamiflu will work against avian flu, adding: "The disease goes so quickly to high levels of infection, you might need to take it before you get exposed."

But as of last week the United States had enough Tamiflu to treat only 2.3 million cases, with 2 million more about to be delivered and a further 8 million on order. Government plans call for a stockpile adequate to treat 20 million people with antivirals. Dr. Irwin Redlener, director of the National Center for Disaster Preparedness at Columbia University, says the government was too slow to order it. Much of Roche's production is now committed to other countries that placed orders earlier. Redlener estimates that it could take until 2008 before production can catch up with worldwide demand for the drug. "We're playing Russian roulette with public health here," he says.

Of course, that's just what the administration doesn't want anyone to think, which explains the flurry of activity last week. That included briefings for congressional leaders under a top-secret security classification ordinarily used only for highly sensitive foreign intelligence; a source familiar with the issue who requested anonymity in discussing intelligence matters speculated that the briefings included information about human cases in foreign countries. The week culminated with a conference of health officials from 80 foreign countries and a well-publicized meeting in which Bush urged drug-company executives to speed their work on vaccines. Secretary of Health and Human Services Michael Leavitt says Bush brought up avian flu with him at a meeting earlier this year, and that "we've been in an aggressive mode of planning for at least six months. Any suggestion the president hasn't been fully engaged on this pre-Katrina would be wrong." Whether he did enough, we may find out this winter, or next. Or, if we're lucky, not at all.

The Race Against Avian Flu | News
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