BOOKS AND ARTS SEPTEMBER 12, 2005
Wherever you look nowadays, you read that a deadly flu pandemic is coming. "A flu nightmare," blared a recent editorial in The Boston Globe; The New York Times ran the breathless "When A Bug Becomes A Monster." Then there was the BBC's "Avian Flu 'Could Cripple Economy'" and Der Spiegel's "A Ticking Time Bomb In Your Backyard." Nature's editors wrote, "Millions of people killed in highly developed countries within months. Tens of millions worldwide. The global economy in tatters. A Hollywood fantasy? No--it's now a plausible scenario." All of which make widespread disease, death, and general chaos seem unavoidable.
The avian influenza, or H5N1 as it is known to scientists, has sparked this attention, with press coverage painting a frightening picture. Pandemic preparations are ongoing: Tests on a new U.S. vaccine recently generated some optimism. But, since the human-to-human communicable disease it is intended to prevent does not yet exist, no one knows whether that vaccine could protect us against a real pandemic strain. Health experts are predicting the worst. Klaus Stohr of the World Health Organization (WHO) claims that seven million will die worldwide; Shigeru Omi, also of the WHO, says it's 100 million, while Russian virologist Dmitri Lvov expects one billion fatalities. Is the Big Flu coming? Judging from such predictions, it must be.
But it's not. The expert predictions don't take into account the evolutionary events necessary to turn an avian flu virus into a mass human killer. In ignoring the evolution of infectious disease, flu experts, science writers, and public health officials are leading us down the same path we've followed too many times before, with Swine Flu, Ebola, and Severe Acute Respiratory Syndrome (SARS). Each new threat produces a new panic, whether panic is warranted or not.
The ur-texts for the killer-diseases-are-coming discourse are Richard Preston's The Hot Zone and Laurie Garrett's The Coming Plague: Newly Emerging Diseases in a World Out of Balance. The central idea of these books--that new infections are waiting in nature to threaten the survival of the human species—is riveting and frightening. But it's also largely off-base. As a new field called evolutionary epidemiology is proving, it's not animal diseases but those adapted to humanity that cause the most trouble.
For one thing, zoonoses--diseases, such as Ebola, Marburg, or Lassa Fever, that come from animals--are typically difficult to transmit between people. These diseases generally lack the essential characteristics identified by evolutionary epidemiologist Paul W. Ewald, of the University of Louisville, as hallmarks of virulent human infections. Lethal human diseases must be either durable in the external environment (like smallpox), waterborne (like cholera), mosquito-borne (like falciparum malaria), carried by hospital workers (like multiple antibiotic-resistant staphylococcus), or sexually transmitted (like AIDS). Or they have to evolve under highly specific conditions, which we call "disease factories." For acute infections, disease factories are situations where people immobilized by illness can readily, and repeatedly, transmit that illness to the well. Most zoonoses don't have the right characteristics, or the right circumstances, to evolve into effective human pathogens.
But figuring out the evolutionary potential of new diseases, which has to be done one germ at a time, is less glamorous than proclaiming that the world is out of balance and new plagues are inevitable. Fear sells--and brings grant money. The avian flu has attracted a host of alarmists, ranging from The Coming Plague's Garrett to Julie Gerberding, director of the Centers for Disease Control and Prevention (CDC), who warned the American Association for the Advancement of Science in February that bird flu "is the greatest threat we are facing." Last week, she claimed H5N1 would be showing up soon, via migratory birds, in Alaska. And, among these doomsayers, none has been more strident than former Minnesota Department of Health epidemiologist Michael T. Osterholm, now head of the University of Minnesota Center for Infectious Disease Research and Policy.
In a series of articles for the New England Journal of Medicine, Nature, and Foreign Affairs, Osterholm threatens us with nothing less than the end of civilization. He opens the Foreign Affairs piece, "Preparing for the Next Pandemic," with the statement: "Dating back to antiquity, influenza pandemics have posed the greatest threat of a worldwide calamity caused by infectious disease." But to say that influenza pandemics pose a threat of "worldwide calamity" is to ignore the fact that--with the exception of the so-called Spanish flu of 1918-1919, which, reports suggest, killed 20 to 50 million people, including an estimated 675,000 Americans--no flu pandemic has been characterized by great mortality, let alone social disruption. In 1957-1958, the Asian flu sped around the world, killing perhaps 70,000 people in the United States--twice the toll of an ordinary flu year, but a long way from 1918. The next pandemic, the Hong Kong flu in 1968-1969, killed about 34,000 in the United States, fewer than the 36,000 Americans who die from flu in an ordinary year, according to the CDC. Human flu is normally a mild to moderately virulent disease: The nature of flu, transmitted via respiratory droplets, means that the virus needs to keep its host walking around, sneezing into other people's faces, and shaking their hands if it's going to spread. Compared with plague (death rates of 60 to 99 percent of those infected) or smallpox (30 to 50 percent), it's a piker. As Ewald argues, and as historian Carol Byerly's recent book Fever of War demonstrates, only the precise conditions of World War I's Western Front—a true disease factory--could have created a flu as virulent as the one responsible for the 1918 pandemic. With people immobilized by illness lying shoulder to shoulder beside the uninfected in trenches, trucks, trains, and ships, the normal brakes to flu virulence were off. The virus didn't need to keep people well enough to walk about--fresh victims were close at hand.
But now, Osterholm says that even the Spanish flu would be nothing compared with what awaits us next year, or next week. He forecasts that, because of population growth, the next pandemic will claim 180 to 360 million people (1.7 million in the United States alone)--and that's assuming the disease is no more lethal than the 1918 flu.
Osterholm has been on the disease and terrorism circuit for a long time. In November of 1997, he published an article in Newsweek stating that the smallpox virus was in the hands of several rogue states, possibly including Iraq. He briefed Jordan's King Hussein on bioterrorism: In 1999, at a symposium held by the Johns Hopkins Center for Civilian Biodefense, Osterholm said, "If there's any doubt whether Iraq has smallpox, His Majesty told me a month before he died that he knew Iraq had smallpox." This claim formed much of the basis for the Bush administration's belief that Saddam Hussein's bioweapons program had illegal stores of smallpox. "Osterholm's story had a significant impact in high places" in the run-up to war, says one administration official.
In the wake of the hysteria over West Nile virus, which entered the United States in the summer of 1999, Osterholm threatened us with deadlier mosquito-borne infections, such as Rift Valley fever, malaria, and dengue. "It's going to happen," Osterholm told a 2003 meeting of mosquito-control experts. "As water runs down a hill, it's going to happen."
It hasn't happened. There have been no large-scale lethal epidemics of mosquito-borne diseases in the United States since malaria was wiped out in the 1940s. There are two reasons for this, according to Ewald: screens and air-conditioning. "Dengue comes across the border every year from Mexico," says Ewald. "It can't take hold here." Mosquitoes can't get to us in large enough numbers to establish a human disease pool.
There's no question that H5N1 avian flu, which first emerged in Hong Kong in 1997, is a deadly disease in birds. Its virulence evolved in the crowded chicken farms and markets of Asia, where thousands of birds are packed into filthy cages-- disease factories for chickens. Zoo tigers and other mammals fed contaminated meat have also died of it; ducks, who are often asymptomatic, have spread the germ through their feces to other water birds. With so many infected creatures across Asia, there is a lot of opportunity for people to come into contact with the virus.
A total of 112 people are known to have contracted avian flu since December 2003, and 57 have died of it--a death rate of over 50 percent. If that rate held and the disease became as transmissible as normal human flu, we would be looking at destruction worse than the Black Death, worse than any catastrophe humanity has ever witnessed.
One problem, though, is that we don't actually know H5N1's true mortality rate. We have no idea how many people in Asia contracted H5N1, came down with a mild infection, and became immune. Research from 1992 has shown that Asian chicken farmers have antibodies to many different forms of the H protein, including H5, in their blood. That's not uncommon: according to University of Ottawa molecular virologist Earl Brown, chicken farmers in North America have antibodies to bird flu strains.
And, in Asia, there are millions of chicken farmers. Prince of Songkla University physicist Sikke Hempenius, a close observer of the outbreak, points out that there are two million in Thailand alone. There are also the many abattoir women who slaughter poultry. There have been billions of chicken/human interactions over the past two years. According to Hempenius, there hasn't been a single case of H5N1 flu among chicken farmers or abattoir women in Thailand. Have they been exposed to the disease? How could they not be, with millions of infected birds all over Asia? Are they, in effect, vaccinated against H5N1? Only if massive blood surveys were carried out could we know for sure--but no one has done this work.
The flu chorus says that bird flu has only to mutate and gain transmissibility among humans to start the deadly ball rolling. In her Foreign Affairs piece, "the next pandemic?," Garrett puts it this way: "If the relentlessly evolving virus becomes capable of human-to-human transmission, develops a power of contagion typical of human influenzas, and maintains its extraordinary virulence, humanity could well face a pandemic unlike any ever witnessed."
There is no question that the flu virus mutates rapidly; this is one of the major sources of concern by molecular virologists, many of whom feel that a chance mutation may be enough to push H5N1 into becoming transmissible from person to person. But these chance mutations would have to occur in the right context. (Mutations that happened while the virus circulates among chickens, for instance, are unlikely to matter much to the disease's human transmissibility.) As virologist Peter B. Jahrling, chief scientist at the National Institute of Allergy and Infectious Disease, says, "Mutations without selection have no consequence."
Furthermore, the panic purveyors don't seem to consider what transmissibility means from the germ's perspective: It is the way in which germs cause symptoms in the host that allows them to leave that host and infect another. With a respiratory infection, this generally means that germs must be shed in coughing, sneezing, or simply mouth-breathing. But the few autopsies that have been performed on H5N1 victims reveal virus deep in the crevasses of the lung tissues, not in the major airways, where you'd expect to find an infectious flu, according to Brown. And a recent study on health care workers in Thailand who cared for avian flu patients shows that, out of 25 workers, not one had been infected, even subclinically. Only in one case, involving a mother and daughter in Thailand, is human-to-human transmission considered probable. In other words, transmissibility among humans is more than just one random tweak of the bird flu genome away.
Even if H5N1 were to become easily communicable among humans, mass death would not follow. Our experience with the SARS coronavirus is instructive. Like avian flu, SARS emerged out of the disease cauldron in East Asia, where domestic animals, wild animals kept in cages as exotic specialty foods, and humans all exist in close proximity. Thought to be a disease of civet cats, SARS, through mutation, acquired the ability to infect human cells. Some time in late 2002, it began to spread among people. But its transmission was erratic. Most people never spread the virus at all, while some individuals, for unknown reasons, infected large numbers of people in a single instance. Even though the disease—which killed about 800 people out of around 8,000 known to have been infected--popped up in several countries around the globe, it never became a pandemic, as prompt public health measures broke the chain of transmission.
Ewald argues that the SARS virus, had it continued to spread, would have evolved to become more effective at transmission. But, by keeping its host mobile, it would also have become less virulent. By Ewald's reasoning, if avian flu starts to move from person to person, its virulence should drop, too--so long as great numbers of people immobilized by illness are not packed into close quarters with the healthy. This sort of disease factory does not exist today. Ordinary crowding won't do it. You need conditions like the Western Front in World War I to allow virulent, transmissible human flu strains to evolve.
Flu hysteria has been rising for many months now. The pandemic is no closer. Reading Garrett's article in Foreign Affairs, you sense she's hedging her bets. "In short, doom may loom. But note the 'may'…nothing at all could happen. Scientists cannot predict with certainty what this H5N1 influenza will do." That is not true. Evolutionary biology tells us that the worst-case scenario--a lethal, transmissible, world-destroying flu--cannot happen, any more than Ebola or Marburg can steal out of the jungle and destroy the human race. If we have an H5N1 flu pandemic, which is certainly possible, we have no logical reason to believe it will be deadlier than the pandemics of 1957 and 1968. We do not need "a new Manhattan Project," in Osterholm's terms, to protect us from pandemic flu. We need an inoculation to protect us from disease hysterics.
Wendy Orent, a science writer, is the author of Plague.
By Wendy Orent