- By Moises Velasquez-Manoff - June 29, 2008 - The New York Times
In the early 1990s, Joel Weinstock, a gastroenterologist, encountered a puzzle. The prevalence of inflammatory bowel disease (I.B.D.) across North America increased markedly during the 20th century. Many thought that "bad" genes would eventually explain the spike, but Weinstock didn't buy it. In areas where fewer than two generations ago the I.B.D. incidence might have been as low as 1 in 10,000, it was now 1 in 250. A defective gene couldn't spread that quickly, he reasoned. It had to be something in the environment. But what? Stumped, Weinstock tried turning the question around. Instead of asking what triggered I.B.D., he asked what, before the 20th century, protected against it?
At the time, Weinstock, then at the University of Iowa, was editing a book on parasitic worms. These worms, or helminths, have a paradoxical effect on the host. Rather than induce inflammation, which is the body's typical response to invasion, the intruders calm the host immune system. They force a peace, scientists think, to avoid eviction and keep the host -- their home and food source -- as healthy as possible. As Weinstock considered the I.B.D. puzzle, he wondered if immune manipulation by worms could incidentally protect against other diseases.
Comparison of the prevalence of I.B.D. and surveys of worm-infestation rates revealed a telling pattern. About 10 years after improved hygiene and deworming efforts reduced worms in a given population, I.B.D. rates jumped. Weinstock had his hypothesis: after a long coevolution, the human immune system came to depend on the worms for proper functioning. When cleaner conditions and new medicines evicted the worms from our bodies, the immune system went out of kilter. "Hygiene has made our lives better," says Weinstock, now at Tufts University. "But in the process of eliminating exposure to the 10 or 20 things that can make us sick, we're also eliminating exposure to things that make us well."
At the time of Weinstock's initial musings, epidemiologists had already dubbed this notion "the hygiene hypothesis": as improved hygiene reduced exposure to certain infectious agents, the immune system began malfunctioning. By the late 20th century, autoimmune disorders, characterized by the body's defenses attacking some aspect of the self, had increased markedly, and allergic diseases, defined by an overblown immune response to nonthreatening substances, afflicted almost half the people in the developed world.
If eliminating worms led to an increase in disease, could re-introducing worms actually treat these diseases? In mice, the answer was yes. Worms were used to "inoculate" against mouse asthma, Type 1 diabetes, multiple sclerosis and I.B.D. But how to re-worm humans? We got rid of them for a reason. Too many worms can lead to anemia or obstructed bowels. The wrong kind can cause considerable suffering, even death.
Weinstock spotted a prime candidate on pig farms. Pig farmers are chronically exposed to Trichuris suis, the pig whipworm, and tolerate it with no apparent side effects. (This is not the potentially dangerous worm found in undercooked pork.)
In 2005, he published results from two human studies. After ingesting 2,500 microscopic T. suis eggs at 3-week intervals for 24 weeks, 23 of 29 Crohn's patients responded positively. (Crohn's disease belongs to the I.B.D. family, which also includes ulcerative colitis.) Twenty-one went into complete remission. In the second study, 13 of 30 ulcerative colitis patients improved compared with 4 in the 24-person placebo group.
Scientists around the world are intrigued. Several large studies are under way. Trials using T. suis eggs on patients with multiple sclerosis, Crohn's and hay fever are beginning in the United States, Australia and Denmark, respectively. In Germany, scientists are planning studies on asthma and food allergies. Other European scientists, meanwhile, plan to replicate many of these experiments with Necator americanus, a human hookworm.
When scientists unravel how helminths manipulate the immune system -- work is already under way -- Weinstock foresees new worm-based drugs. But that may be a long way off, he says. Anyway, the pill approach risks missing the greater lesson. As he says, "We're part of our environment; we're not separate from it." It's a simple observation with profound implications that are changing how scientists view the human organism. The dawning realization is this: You are not just your genetic self. You are a community of interacting organisms. This You ecosystem includes the bacteria that outnumber your genetic cells by 10 to 1, various fungi, viruses and just maybe a few parasites as well. Disturb or remove any key player, and the whole system can come unbalanced.
Moises Velasquez-Manoff is a writer living in New York.