There are some words—terrorism or cancer, for instance—that evoke such fear, we try not to breathe them out loud, as if speaking the name of those evils could increase their capacity to harm us.
Ironically, it's the taboo quality of these words that make them appealing choices for headlines. They seize our attention and quicken our pulse: We can't look away. Fear drives our thirst for information.
"Pandemic"—the worldwide outbreak of a disease—is a prime example of this category. Though few are alive who remember the flu pandemic of 1918-19, its specter still haunts us. The deadliest of the 10 flu pandemics that have struck the world over the last 300 years, the so-called Spanish flu strain began as an avian influenza virus, mutated into a form that passed between humans, infected a fifth of the world’s population, and killed up to 50 million people, including more than 650,000 in the United States.
Today, it is avian flu H5N1 the most virulent subtype of the influenza A type viruses, that has set the world on edge. (Influenza viruses are classified as A, B or C types, though in recent years, only the subtypes of influenza—particularly H1N1, H1N2 and H3N2—have been circulating in human populations, causing seasonal flu outbreaks. All pandemic-causing viruses have also been type A and some suggest that H5N1 resembles 1918's deadly strain.)
Since its initial 1997 outbreak among poultry and humans in Hong Kong, this highly infectious virus has spread from Southeast Asia into Europe, Africa, and the Middle East. As of this writing, scientists and media are turning their focus to Alaska, where avian flu is expected to make its first North American stop within weeks, brought ashore by migratory water birds returning from their winter stay in Asia. By many predictions, it will hit the West Coast by autumn.
Mapping mutations
While hundreds of millions of birds, primarily chickens, have died from the disease or mass exterminations of exposed flocks—with losses in the billions for poultry industries in affected countries—H5N1 is far from reaching pandemic status among human populations. Scientists are quick to remind the public that although H5N1 is clearly a dangerously lethal virus, it is first and foremost an avian disease. To date, birds—not people—are its predominant "hosts" and victims. So far, there are still no corroborated cases of human-to-human (or "H2H" in bird-flu parlance) transmission. The people who've contracted the virus and died from it have been predominantly poultry farmers or workers in live bird markets who had extremely close, prolonged contact with infected animals.
Eddie HolmesCredit James Collins
In fact, says Penn State virologist Edward Holmes, though each human death from H5N1 is a tragic loss, the total human death toll is just over 100. "You've got to put it into context," urges Holmes. "Every year, 36,000 people die of normal, seasonal flu. That's a large number of deaths."
British-born and Cambridge-educated, Holmes pads around his offices in University Park (where posters of viral genetics share wall space with an homage to Homer Simpson) looking more like the boy-genius-next-door than an integral member of the university's pioneering Center for Infectious Disease Dynamics. ("Call me Eddie," he says.)
His latest endeavor? "I'm involved in an unofficial capacity with the National Institutes of Health's Influenza Genome Sequencing Project on how human flu evolves from season to season," says Holmes. "We have to decipher the dynamics of 'normal' seasonal human flu and we don't have that completely understood yet," he explains. "There's been a lot of dogma for thirty odd years about how the virus does what it does and it hasn't really been challenged until now."
What the influenza virus does—and does extremely well—is mutate. In particular, RNA viruses such as influenza replicate very quickly, making lots of mutations—essentially, transcription errors—as they go. Not possessing the "repair kit" enzyme polymerase that is present in DNA viruses, they can't correct their replication. "And what happens," says Holmes, "is that a subset of those errors turns out to be beneficial to the virus and allows it to spread more efficiently through populations."
Outsmarting viral evasion
"This NIH study," he enthuses, "is a huge genomics project, sequencing hundreds—thousands!—of flu genomes from around the globe. But the clever thing is that, rather than doing a random sampling from different populations, this is a micro-evolutionary study that analyses the flu's diversity in a single population over several years."
One goal of the NIH study is to better understand how the highly variable flu virus often evades our attempts to immunize against it—an event described in the biomedical community as "vaccine failure." In the seven years of this ongoing study, the intensity of focus and "fine level analysis" have yielded "an absolute gold mine" of information about flu evolution, says Holmes.
"It's far more complicated than we knew," he adds. "What we've shown is that flu viruses can exchange genes—in a process called reassortment or recombination—more than we ever thought they did before. Most of the new variations it creates won't be particularly useful to it, but it's turning over phenomenally quickly—I can calculate the rate of evolution per day in the virus—and what appears to happen is that every few years, the virus makes a bigger jump in evolutionary space than we can predict."
A better understanding of this process, declares Holmes, is "fantastically important" if we hope to protect ourselves against both garden-variety seasonal flu and potential pandemics caused by high-mortality strains such as H5N1. (Compared to the typical one percent annual flu mortality rate, H5N1 appears to be killing up to 55 percent of its human victims and 100 percent of infected domestic poultry. Initial human clinical trial results testing an experimental H5N1 vaccine suggest "limited effectiveness".)