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http://www.nytimes.com/2002/12/24/health/24ESSA.html

Can Dirt Really Be Good for People? Maybe. But a Little Goes a Long Way.

By KENT A. SEPKOWITZ, M.D.

n the last year, the world of infectious diseases has begun to lose its bearings. The simple John Wayne-like world where the good guys (vaccines, antibiotics and hand washing) chase away the bad guys (bacteria, viruses and all the rest) is fading fast into the sunset.

Rather, some investigators are arguing that, contrary to your mother's (and everyone else's) advice, many of us are not receiving enough infections. Writing recently in The New England Journal of Medicine, Dr. Scott Weiss of the Channing Laboratory at Harvard, referred to the new focus as the "eat dirt" approach to health.

The idea, although perhaps unsettling, is neither new nor that complicated. As miserable as infections make us feel in the here and now, routine constant low-grade colds, flus and stomach viruses represent useful assaults on our immune systems. As such, they resemble the relentlessly upbeat personal trainer who preaches the doctrine of no pain, no gain. Infections keep us, and our immune systems, fit and ready to go.

A result is an immune system of great sophistication, forever primed to tackle the various assaults that lie ahead. The final consequence of all of this, according to the theory, is that — maybe — those who grow up in less hygienic, less germ-free and less vaccine-punctured environments have substantially lower rates of an array of autoimmune and allergic diseases like multiple sclerosis, Crohn's disease, asthma and eczema.

The story is a classic medical tale of epidemiologic observation, leading first to head scratching, then to a flurry of guesses and high-end theories and, finally, to basic scientific evidence to buttress the initial observation. In the 1960's, epidemiologists observed a surprising trend. Children in affluent Westernized societies, according to design, had decreasing rates of various infectious diseases, courtesy of clean water, vaccinations, well-scrubbed houses and pasteurized milk.

But there was an unexpected twist. In those same families, rates of other diseases, loosely grouped together as autoimmune or allergic conditions, demonstrated a startling increase. Still, an epidemiologic association does not a cause make. Consider what is apparently an association, say, between the decline of West Nile virus cases in New York and Mayor Michael R. Bloomberg's election. Or the rise in syphilis cases in the United States soon after George Harrison died.

Good old-fashioned coincidence does indeed still occur, and in most situations it is the most likely explanation. In medical parlance, that circumstance is referred to as "true, true and unrelated."

So how did the "eat dirt" observation become a hot new area of scientific investigation? The first order of business with any simple epidemiologic observation is to try to shake out any confounding factors that might make things seem causally linked when in fact they are simple coincidence.

Perhaps what we are measuring is not what we think we are measuring. Maybe children who live in cleaner houses and receive regular vaccinations are exposed to something different from children who live in less well-off surroundings. Those differences could be in the types of paint used in their houses, the foods they eat, their parents' ages, family size, the likelihood of a mother's drinking or smoking or exposure to well water or electromagnetic waves. There can be as many theories as people willing to devise them.

Such explanations held sway for a few decades. But they could not quite accommodate the entire story, especially the "hygiene paradox" noted among children who grew up on farms. Such upbringings differ in many ways, of course, from urban childhoods.

More fresh air, smaller schools with fewer children, animals all over the place and no fast food. The list is endless. To get around that, researchers compared farm children to youngsters in small rural environments but not on farms, and they still found a distinct difference in rates of autoimmune and allergic conditions. Something was unique to the farm, not just the country life.

Finally, researchers made a breakthrough observation. They found endotoxin in high quantities in mattress dust taken from children's bedrooms. Endotoxin is a crucial component of many bacteria found in high quantities in the feces of large farm animals. Thus its presence in mattresses on farms.

The investigators were able to establish a strong association between endotoxin levels in mattress dust and rates of allergic and autoimmune conditions. The more dust, the lower the risk.

That made good biologic sense. Certainly endotoxin can influence the entire web of interlocking inflammatory proteins, called cytokines, and their more recently identified molecular cousins, the defensins and the collectins. Perhaps endotoxin was provoking a regular vigorous workout of the developing immune system, teaching the inflammatory proteins how to behave, thereby promoting smooth immune maturation.

That would lead to the observed decrease in certain types of autoimmune and allergic conditions, which may stem from overexuberant immune responses. Makes sense, right?

Not entirely. Because at too large a dose, endotoxin is the immunologic equivalent of the atom bomb. The inflammatory network suddenly explodes, and the patient goes into shock and usually dies. Indeed, in the extremely ambivalent world of medicine and biology, few products have a role as double-edged as endotoxin. Good guy or bad guy, depending on your perspective, the ultimate postmodern hero. Goodbye, John Wayne, and hello, Don Corleone.

The notion that infections and dirt may be good and cleanliness bad is a tough one for the hygiene-obsessed to fathom, much less accept. It is also a theory that is easy to overstate.

Certainly the progress in eradicating infectious killers like measles and hepatitis, as well as the crowning achievement of Western civilization, adequate plumbing to prevent gastrointestinal infections, far outweigh the potential harm our approach to germ control may cause.

But by following this seemingly illogical lead, researchers may have stumbled on a crucial clue in the search for understanding the intimate relationship between human health and disease.
 

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