by Judith Hooper
The Atlantic Monthly: Feb 1999

Excerpts:

The dictates of evolution virtually demand that the causes of some of humanity's chronic and most baffling "noninfectious" illnesses will turn out to be pathogens -- that is the radical view of a prominent evolutionary biologist

These Darwinian laws have led Ewald to a new theory: that diseases we have long ascribed to genetic or environmental factors -including some forms of heart disease, cancer, and mental illness- are in many cases actually caused by infections.

"When diseases have been present in human populations for many generations and still have a substantial negative impact on people's fitness," he says, "they are likely to have infectious causes."

Although its fitness-reducing dimensions are difficult to calculate, the ordinary stomach ulcer is the best recent example of a common ailment for which an infectious agent -- to the surprise of almost everyone -- turns out to be responsible.

When I visited him one afternoon, Ewald pulled off his shelves a standard medical textbook from the 1970s and opened the heavy volume to the entry on peptic ulcers. We squinted together at a gray field of small print punctuated by subheads in boldface. Under "Etiology" we scanned several pages: environmental factors ... smoking ... diet ... ulcers caused by drugs ... aspirin ... psychonomic factors ... lesions caused by stress. In the omniscient tone of medical texts, the authors concluded, "It is plausible to hypothesize a wealth of these factors...." There was no mention of infection at all.

In 1981 Barry J. Marshall was training in internal medicine at the Royal Perth Hospital, in Western Australia, when he became interested in incidences of spiral bacteria in the stomach lining. The bacteria were assumed to be irrelevant to ulcer pathology, but Marshall and J. R. Warren, a histopathologist who had previously observed the bacteria, reviewed the records of patients whose stomachs were infected with large numbers of these bacteria. They noticed that when one patient was treated with tetracycline for unrelated reasons, his pain vanished, and an endoscopy revealed that his ulcer was gone.

An article by Marshall and Warren on their culturing of "unidentified curved bacilli" appeared in the British medical journal The Lancet in 1984, and was followed by other suggestive studies. For years, however, the medical establishment remained deaf to their findings, and around the world ulcer patients continued to dine on bland food, swear off stress, and swill Pepto-Bismol. Finally Marshall personally ingested a batch of the spiral bacteria and came down with painful gastritis, thereby fulfilling all of Koch's postulates.

There is now little doubt that Helicobacter pylori, found in the stomachs of a third of adults in the United States, causes inflammation of the stomach lining. In 20 percent of infected people it produces an ulcer. Nearly everyone with a duodenal ulcer is infected. H. pylori infections can be readily diagnosed with endoscopic biopsy tests, a blood test for antibodies, or a breath test. In 90 percent of cases the infections can be cured in less than a month with antibiotics. (Unfortunately, many doctors still haven't gotten the news. A Colorado survey found that 46 percent of patients seeking medical attention for ulcer symptoms are never tested for H. pylori by their physicians.)

Heart disease is now being linked to Chlamydia pneumoniae, a newly discovered bacterium that causes pneumonia and bronchitis.

While examining coronary-artery tissues at autopsy in 1991, Allan Shor, a pathologist in Johannesburg, saw "pear-shaped bodies" that looked like nothing he'd ever seen before. He mentioned his observations to a microbiologist colleague, who had read about a new species of chlamydia with a peculiar pear shape. The colleague referred Shor to an expert on the subject, Cho-Chou Kuo, of the University of Washington School of Public Health, in Seattle. After Shor shipped Kuo the curious coronary tissue, Kuo found that the clogged coronary arteries were full of C. pneumoniae. Before long, others were reporting the presence of live C. pneumoniae in arterial plaque fresh from operating tables. Everywhere the bacterium lodges, it appears to precipitate the same grim sequence of events: a chronic inflammation, followed by a buildup of plaque that occludes the opening of the artery (or, in the case of venereal chlamydia, a buildup of scar tissue in the fallopian tube). Recently a team of pathologists at MCP-Hahnemann School of Medicine, in Philadelphia, found the same bacterium in the diseased sections of the autopsied brains of patients who had had late-onset Alzheimer's disease: it was present in seventeen of nineteen Alzheimer's patients and in only one of nineteen controls.

By the mid-1990s a radical new view was emerging of atherosclerosis as a chronic, lifelong arterial infection. "I am confident that this will reach the level of certainty of ulcer and H. pylori," says Saikku, who estimates that at least 80 percent of all coronary heart disease is caused by the bacterium.

H. pylori, the ulcer pathogen, confers a sixfold greater risk of stomach cancer, and accounts for at least half of all stomach cancers. Also, the lymphoid tissue of the stomach can produce a low-grade gastric lymphoma under the influence of this bacterium. Early reports indicate that the lymphoma is cured in 50 percent of cases by resolving the H. pylori infection -- which may mark the first time in medical history that cancer has been cured with an antibiotic.

Hepatitis B and C, two of the ever-growing alphabet soup of hepatic diseases, have been linked to liver cancer. Herpes virus 8 has recently been discovered to be the cause of Kaposi's sarcoma. "There is no reason to believe that this flurry of discovery has now completed the list of infectious agents of cancer," Ewald says.

Among the many known animal cancer viruses is a closely studied retrovirus known as mouse mammary tumor virus (MMTV), which causes mammary-gland cancer in mice.

Microbes obviously can cause mental disorders -- as syphilitic dementia, to name but one example, makes brutally clear.

Multiple sclerosis seems pretty clearly infectious, because you have these island populations where there was no MS and then you see it spread like a wave through the population. And you have this latitudinal gradient ... "Yes!" Cochran burst from the speaker phone. "The farther you get from the Equator, the more common it is. It's three to four times more common if you grow up in Ontario than if you grow up in Mississippi."

Of the top forty fitness-antagonistic diseases on the list, thirty-three are known to be directly infectious and three are indirectly caused by infection; Cochran believes that the others will turn out to be infectious too. The most fitness-antagonistic diseases must be infectious, not genetic, Ewald and Cochran reason, because otherwise their frequency would have sunk to the level of random mutations. The exceptions would be either diseases that could be the effect of some new environmental factor (radiation or smoking, for example), or genetic diseases that balance their fitness cost with a benefit. Sickle-cell anemia is one example of the latter.

No doubt everywhere people look there will be more and more examples of chronic diseases with infectious etiology," says Stephen S. Morse, an expert in infectious diseases at the Columbia University School of Public Health. "Helicobacter is probably the tip of the iceberg." Although we have wielded the tools of microbial cultivation for a hundred years, much of the microbial world is still as mysterious as an alien planet. "It has been estimated that only 0.4 percent of all extant bacterial species have been identified," David Relman has written. "Does this remarkable lack of knowledge pertain to the subset of microorganisms both capable of and accomplished in causing human disease?" Even the germs that inhabit our bodies -- the so-called "human commensal flora," such as the swarming populations of organisms that live in the spaces between our teeth -- are largely unknown, he points out. Most of them are presumably benign, up to a point. There are disquieting suggestions in the literature of a link between bacteria in dental plaque and coronary disease.

"Some people think it's scary to have these time bombs in our bodies," Ewald says, "but it's also encouraging -- because if it's a disease organism, then there's probably something we can do about it. The textbooks say, In 1900 most people died of infectious diseases, and today most people don't die of infectious disease; they die of cancer and heart disease and Alzheimer's and all these things. Well, in ten years I think the textbooks will have to be rewritten to say, "Throughout history most people have died of infectious disease, and most people continue to die of infectious disease."