The Real Hot Zone

Back in the 1880s, before tuberculosis had a known cause, experts attributed it to a combination of risk factors--things like depression, bad ventilation, insufficient food and "family predisposition." One standard textbook noted expansively that "the idea of infection being a cause... still prevails in the South of Europe." Fast-forward to the 1980s, and you hear similar accounts of peptic ulcers. The highly touted risk factors were stress, smoking, alcohol and, of course, "genetic predisposition." Never mind that an Australian researcher named Barry Marshall was successfully giving himself ulcers by swilling beakers of bacteria--and curing them with antibiotics. The textbooks didn't even mention his work.

We now know that TB and ulcers are infectious conditions, caused by specific microbes and treatable with antimicrobial drugs. Yet we're still laboring to explain most of our leading scourges--cancer, heart disease, mental illness, Alzheimer's--with long lists of risk factors. In a compelling new book titled "Plague Time" (282 pages. Free Press. $25), Amherst College biologist Paul Ewald argues that we're missing an obvious lesson here. Roughly translated: It's the germs, stupid. Though genes and lifestyle are no doubt important, Ewald says, the primary causes of today's "slow-burning plagues" are parasites--viruses, bacteria and other infectious microbes--whose long-term effects we have simply failed to recognize.

Ewald is not a virologist but a bold-minded evolutionist who, in past work, has created a whole new framework for thinking about infectious disease. To understand why microbes behave as they do, he considers their ecological incentives. Cold viruses can't afford to be too virulent because they require mobile hosts. (A dying cold sufferer wouldn't get around enough to infect other people.) But parasites that can survive outside their hosts don't have to be so considerate--especially if they can travel from host to host via mosquitoes or drinking water. A dying malaria sufferer is, if anything, preferable to a healthy one from the parasite's perspective. All the person has to do to spread infection is lie still and get bit.

In "Plague Time," he takes a similar approach. By his reasoning, our genes shouldn't cause much heart disease, mental illness, cancer or autoimmune disease. Genes that impede our survival tend to die out over time, as their owners fail to reproduce. By contrast, the parasites with the best tricks for exploiting us are the most likely to stay in the game. There is no question that viruses and bacteria can take up long-term residence in our bodies. Some hide deep within our cells to avoid detection by the immune system, while others disguise themselves to resemble our own tissues. And we know the consequences can be serious. Suppose the immune system catches sight of a streptococcal bug that normally evades detection by masking itself as a heart cell. As the body attacks the invader, it may demolish the organ as well.

The question is whether these chronic infections are as pervasive as Ewald suspects. Some experts would scoff at the notion, but the recent findings are impressive. "Until the 1980s," he writes, "it was generally not appreciated that women who were suffering and dying from cervical cancer were the victims of a venereal disease epidemic." Today it's undeniable. Epidemiologists have puzzled for more than a century over the link between sexual promiscuity and cervical cancer. But over the past 15 years, studies have revealed that human papillomaviruses, America's most common sexually transmitted pathogens, are present in some 93 percent of cervical tumors. Scientists have even identified the proteins that HPVs use to release the brakes on normal cell division.

Cervical cancer may be the tip of an iceberg. Less definitive studies have linked childhood strep infection to obsessive-compulsive disorder and Tourette's syndrome. Traces of a virus that causes mammary cancer in mice have been recovered from human breast tumors. Researchers in Japan and Germany have linked borna virus--a brain infection seen in horses, sheep and cats--to schizophrenia and bipolar disorder in people. And a growing body of evidence suggests that Chlamydia pneumoniae, a common respiratory bug, may play a key role in coronary artery disease, the leading cause of death throughout the Western world. Since 1988, researchers have consistently found the bacterium in clogged vessels but not in healthy ones. They've caused arterial lesions in rabbits by infecting them with the germ. They have even found hints that antibiotics can slow the progression of heart disease in infected patients.

As these connections are borne out, they could change medicine as profoundly during the 21st century as germ theory did in the 20th. The question is whether they'll get the attention they deserve. As Ewald observes, "Those who control access to funding and the channels of scientific communication tend to be believers in the established views." When Edward Jenner hit upon the notion of a smallpox vaccine in 1797, the Royal Society of London scolded him for risking his reputation on something "so much at variance with established knowledge, and withal so incredible." When the Hungarian physician Ignaz Semmelweis figured out that physicians' unwashed hands were causing fatal infections among new mothers at the University of Vienna in the 1850s, he lost his own position there. And though Barry Marshall first reported his findings on the infectious cause of ulcers in 1983, his peers ignored the discovery until 1990, when the National Enquirer got hold of the story and told the world. Let's hope the scientific community is less slow to notice this book.

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