Germs Make The Man Your body is teeming with trillions of infectious microbes. That's a very good thing.
By David Stipp

(FORTUNE Magazine) – Germs. The word conjures up pure evil--killer microbes resistant to every available antibiotic, scratches that become grisly wounds when invaded by flesh-eating Streptococci, terrorists potentially spreading smallpox far and wide. Until a few years ago it seemed as though the war on germs had turned in our favor. Antibiotics made short work of most bacterial infections, and vaccines were gradually wiping out scourges like polio. Then came terrifying setbacks: HIV, Legionnaires' disease, deadly E. coli in burgers. We really didn't need anthrax in the mail to realize that the struggle of humans against microbes is far from over.

There's just one thing wrong with this War of the Worlds vision: It's utterly misleading. Consider the affable germs in our intestines that make vitamin K, essential for clotting blood. Or the benign microbes in our airways--an estimated 65 billion of the bugs live on each square inch of our upper throats and help crowd out dangerous infections. Or the bacteria that got so cozy with higher organisms a billion years ago that they merged with cells to become energy-spinning dynamos called mitochondria--in a way, our very life force springs from these vestigial symbiotic germs, which inhabit every one of our cells, still carrying remnants of their ancient DNA.

Human relationships with microbes are far more varied and complex than the metaphor of war implies. With so many infectious threats looming, we can no longer afford to oversimplify the subtle dynamics at play in our inner germscapes. Urging a major rethink on this issue, Nobel laureate biologist Joshua Lederberg declared in Science magazine in 2000 that "our most sophisticated leap [in dealing with looming infectious threats] would be to drop the Manichean view of microbes --'We good; they evil' "--and replace it with "ecological" metaphors that will inspire smarter ways to ward off disease.

The simplistic nuke-the-fiends mindset has already cost humans dearly. Overuse of antibiotics has engendered strains of deadly bacteria resistant to the drugs. Evidence is growing that allergies, too, may be abetted by our germicidal zeal: When we carpet-bomb our buildings and bodies with antibacterial products, we may be preventing childhood exposure to microbes that's needed to train the immune system not to overreact during later exposure.

Consider a telling study that recently appeared in the Journal of the American Medical Association. It showed that infants in families with two or more pets were up to 77% less likely to develop allergies than kids in pet-free homes. The finding suggests that close contact with animals exposes children to bacteria and dirt that help train their developing immune systems to calmly cope with challenges that otherwise might later provoke allergies. Similarly, kids in large families probably have their grubby siblings to thank for the fact that they are less likely to suffer from allergies than an only child.

Some scientists even suspect that the developed world's rising rates of autoimmune disease, such as juvenile diabetes and multiple sclerosis, are at least partly due to our germphobic lifestyles--such disorders are due to riled-up, half-witted immune cells that zap the body's own tissues.

None of this means that you should abandon the rules of basic hygiene, such as washing your hands after touching raw meat. Nor is warding off diseases with childhood vaccines a bad idea. But it does suggest that we've been had by product ads that urge us to apply disinfectants constantly to ourselves and our surroundings.

As Lederberg notes, there's another cost: Obsessing on microbes' dark side has blinded us to ways we can enlist them to bolster health. True, the idea of exploiting good germs has been around for decades--probiotic foods, ones laced with "good" bacteria such as the Lactobacillus strains in yogurt, have long been touted for their ability to colonize the intestines with beneficial bugs. But the concept has hovered at medicine's fringe. Now, thanks to luminaries like Lederberg and to a recent flurry of studies on the subject, it is gaining overdue respect.

Swedish researchers in 2000 reported that the rate of middle-ear infections in kids prone to earaches was halved by an experimental nasal spray laced with alpha-streptococci, bacteria that normally inhabit the nasal passages and ear tubes. Other preliminary studies over the past few years have shown that patients afflicted with disorders that cause severe bowel inflammation can benefit from doses of probiotic microbes.

Applying similar logic, scientists in New Zealand have sparked excitement in the wine-growing world with a fungus-containing spray called Botry-Zen. When applied to grapevines, the harmless fungus takes over the niche occupied by a grape-rotting mold that strikes fear in the hearts of growers everywhere.

At the University of Florida, researcher Jeffrey Hillman has bioengineered bacteria to prevent cavities. More than 100 kinds of bacteria call the human mouth home, but most cavities are thought to be caused by just one, Streptococcus mutans, which converts sugar in our food to enamel-eating lactic acid. Hillman developed a way to knock out the bacterium's ability to make lactic acid. Then, by screening hundreds of isolates from dental patients' mouths, he found a strain of Strep mutans that behaves as a natural antibiotic against other strains--microbes often out-compete their rivals by poisoning them.

By combining the two qualities--antibiotic plus no lactic acid--in a novel strain of the bacterium, he created a benign bug able to displace even the well-entrenched baddies in plaque. Rodent studies suggest that a single oral application of the microbes might ward off cavities for years. A startup company Hillman founded, OraGenics in Alachua, Fla., hopes to begin testing his tiny tooth fairies in people within a year.

These advances give just a glimpse of what lies ahead. Our bodies are rain forest-rich with microbial ecosystems that we're only beginning to understand. By one estimate, the 90 trillion or so germs living in a healthy adult's skin, airways, colon, and other niches outnumber all the body's cells ten to one. Most are harmless "commensals," from the Latin word for "sharing a table." Many have evolved with us over eons, a process that has molded their genomes to fit our various nooks hand in glove. Indeed, we higher animals might never have existed without commensal bacteria, which keep deadly microbes at bay by crowding them out.

The peaceful coexistence is abetted by friendly conversations that commensals carry on with our cells via chemical signals. A message commonly sent by bacteria to the immune system might be translated as "Don't get excited; it's just me, your old pal." Scientists eavesdropping on the cross-talk between germs and our cells have found signs that it plays a key role in forming the digestive tract and immune system. Mice reared in germ-free incubators, for example, develop grossly abnormal large intestines, and their ability to fight infections is greatly impaired. Cross-talk also explains why antibiotics sometimes trigger bowel inflammation--when our commensals are clobbered, foreign bugs can move in that haven't evolved the language of peace.

Once we identify key commensals and get the hang of their micro-gab, we'll be set to work some miracles of healing. Germs' chemical peace symbols, for instance, might be fashioned into drugs to quell autoimmune disease. And the fact that commensals are tailored to live in particular bodily niches may make them ideal for delivering drugs--niche-specific strains could be bioengineered to add medicines to their chemical communiques, enabling therapeutics to be put where they're most needed. (For safety, extra genes could be inserted in the bugs to make them highly vulnerable to certain antibiotics.)

Of course, realizing the huge promise of probiotics will take a long time. Among other challenges, proponents must convince federal regulators that medically applied infectious organisms won't turn against us. But the case for forging new alliances with our familiar guests has never been more compelling. With scads of bad bugs on the rise, we need all the friends we can get--it's comforting to know that about 90 trillion of them are very close to home.