The Houston Chronicle

American children 70 years ago had a closer relationship with dirt than they do now.

There were fewer sidewalks, paved roads and indoor toilets, and kids spent more time playing outside in their bare feet. As a result of this daily contact with soil, almost all youngsters were infected with intestinal parasites such as hookworms, pinworms or whipworms.

And that was a good thing.
At least that's the thinking of Joel Weinstock, a University of Iowa researcher who believes regular doses of worms may be the key to treating people with inflammatory bowel disease, a serious and baffling disorder that affects at least 1 million people nationwide.

"As we move into our sterile boxes, (breathe) sterile air, we're no longer being exposed to some of the natural agents that may be required for optimal development of our immune systems," said Weinstock, director of the Digestive Disease Center at the University of Iowa Hospitals and Clinics. "As we've de-wormed, people have developed immune systems which are not dampened."

The cause of inflammatory bowel disease, a term that encompasses both ulcerative colitis and Crohn's disease, is a mystery, but it is presumed to result from poor regulation of the intestinal immune system — an overreaction to normal intestinal bacteria.

The diseases usually begin in people during their late teens and 20s and last a lifetime. They cause abdominal pain, diarrhea and gastrointestinal bleeding. Sections of the intestine may become blocked by scar tissue and require surgical removal. Those afflicted are at greater risk for colon cancer.

Currently, there isn't a cure, but antibiotics, steroids, pain and immune-modulating drugs such as cyclosporine help reduce symptoms.

In the United States and other industrialized countries, the disorder is rampant. However, Weinstock notes, the condition is rare in poor countries where parasitic worm infection is common.

Researchers have learned that the intestine houses a complex ecosystem, including 200 to 300 different species of bacteria as well as various viruses and parasites. All of the inhabitants modulate the intestinal immune system, which is largely governed by two types of T-cells, called TH1 and TH2, found in the intestinal lining.

TH1 induces inflammation, TH2 neutralizes the inflammatory response. For unknown reasons, many parasitic infections induce a pure TH2, anti-inflammatory, response.

Weinstock theorizes that man and the lowly worm co-evolved to become interdependent. He believes intestinal worms, or helminths, dampen the immune response so they can thrive in humans. In the absence of these parasites, the human intestinal inflammatory response is unchecked and goes into overdrive, causing disease.

Studies in mice conducted by University of Iowa researchers supported this worm-as-good-guy idea. Mice exposed to helminthic worms were protected from the development of inflammatory bowel disease.

This spring, working with colleagues David Elliot and Robert Summers, Weinstock gave six patient volunteers a drink laced with the microscopic eggs of a worm that doesn't normally infect people. Standard treatments hadn't helped these patients, four of whom had Crohn's disease and two of whom suffered from ulcerative colitis.

Although these worms can survive in the human intestine, reaching nearly a half-inch in length, they can't reproduce and are expelled after a couple of months.

After ingesting the eggs, all six patients improved substantially. Five went into complete remission. The treatment had no noticeable side effects and the patients' improvements lasted one to five months following the single dose.

"These people were doing way, way better than he (Weinstock) hoped in his wildest dreams. He's not saying this is the be-all, end-all. This is something to be studied," said Dr. Peter Ernst, an immunologist at University of Texas Medical Branch in Galveston who is familiar with Weinstock's research. "It's a logical thing to do and so far it seems to work ... And we all hope it does."

Weinstock declined to specify which type of worm he used out of concern that patients might be tempted to try it on their own and inadvertently contract a dangerous parasite.

Dr. Alan Buchman, a professor of gastroenterology at the University of Texas-Houston Health Science Center, called Weinstock's idea "an interesting hypothesis" but said a study of six patients is too small to be definitive. Treatments for Crohn's and colitis typically have a 30 to 35 percent placebo response rate, he said. The placebo effect is a phenomenon in which people experience an improvement in their condition in response to a phony therapy, such as a sugar pill.

Weinstock's team is now organizing a clinical trial with additional patients to compare the treatment with a placebo and see if additional doses help. The double-blind study, in which neither researchers nor patients know who is getting worm eggs and who is getting a placebo until the study's completion, will begin in January.

"A year from now, you might look back and it means nothing," Weinstock said. "The bottom line is, it has potential. We will have to see before we can say for sure it's helping people. But we're encouraged."

Copyright 1999 The Houston Chronicle. All rights reserved.