SCIENCE FILE : War on Germs Is Enough to Make You Sick : Some researchers say the fight against infectious diseases is being waged at the expense of our immune systems. As exposure to such maladies drops, they say, susceptibility to things like bowel disease goes up.
The greatest medical achievement of the 20th century has been improved sanitation. Public health measures to block the spread of disease have saved more lives than all the drugs and medical procedures developed during the century combined.
A small but growing number of researchers are arguing, however, that in saving ourselves from cholera, dysentery, typhoid and a host of other infectious diseases, we may have set ourselves up for a sharp increase in autoimmune diseases.
Repeated exposure to a variety of germs early in life trains the immune system not to overrespond to immunostimulants encountered later in life, they argue.
In the absence of this training, the immune system becomes hyperreactive and mounts an attack against harmless chemicals or foods in the diet. In the process, they say, we become susceptible to such autoimmune diseases as Type 1 diabetes, rheumatoid arthritis, multiple sclerosis and asthma.
These diseases were virtually unknown before modern sanitary measures were introduced into the Western world and are still uncommon in developing countries. They are also more common in the colder, northern latitudes where infectious diseases spread less easily.
Now, another autoimmune disease is being added to the list: inflammatory bowel disease, which affects as many as 1 million Americans. Some researchers have suggested that changes in the bacterial population of the gut associated with improved sanitation are responsible for the dramatic increase in IBD in the latter half of this century.
Worms to the Rescue
But Dr. Joel Weinstock of the University of Iowa has a more radical idea. Experiments he has conducted on animals suggest that widespread exposure to intestinal worms in the early part of this century provided protection against development of IBD and that loss of this exposure through improved sanitary conditions has led to the onslaught of bowel disease.
Moreover, Weinstock and his colleagues have demonstrated in early experiments that infecting IBD patients with these worms--called helminths--can lead to remissions in patients with otherwise intractable bowel disorders. His team is now gearing up to perform much larger clinical trials of the technique.
“It is an intriguing concept that is still quite preliminary at the human disease level,” said Dr. R. Balfour Sartor of the University of North Carolina, chairman of the Crohn’s and Colitis Foundation of America. “But [Weinstock has] got reasonably good support in animal models . . . and it is certainly a promising area to investigate.”
Researchers in Europe are already using unusual bacteria, such as lactobacilli and bisidobacteria, in experimental attempts to treat IBD by restoring the immune balance in the gastrointestinal system. Weinstock is simply using a different organism to achieve the same purpose.
“We are in the early stages of a whole new approach to treating bowel disease,” said Dr. Dan Present of Mt. Sinai Hospital Medical Center in New York City. “If we can alter the environment [in the gut], perhaps we can diminish the immune response.”
Inflammatory bowel disease is an umbrella term that encompasses two gastrointestinal problems--Crohn’s disease and ulcerative colitis--that are in many ways two sides of the same coin. Crohn’s normally occurs in both the small intestine and the large intestine, or colon, while ulcerative colitis is restricted to the colon. Ulcerative colitis affects only the innermost lining of the colon, while Crohn’s affects all layers.
But the symptoms are very similar and include diarrhea, crampy abdominal pain and rectal bleeding. Each disorder is thought to affect about 500,000 Americans, both men and women equally, and they are usually diagnosed before the age of 30. About 20% to 25% of victims have a relative who is also affected, suggesting a genetic susceptibility to the disorders.
The primary treatments are aspirin-like drugs, steroids to suppress the immune system, and stronger immunosuppressive drugs, such as azathioprine and methotrexate. In more severe cases, surgeons remove the affected areas, but the problem usually returns in previously healthy segments of the gut.
Recent studies in several labs indicate that IBD results from an unbalanced immune response in the intestines involving two types of white blood cells, called T-helper-1 and 2, or Th1 and Th2. Th1 cells respond aggressively to foreign substances in the gut, while Th2 cells can dampen that response. In IBD, this system is thought to be out of balance, with the Th1 cells responding too aggressively to normal constituents of the intestines, damaging intestinal walls in the process. Weinstock’s goal is to restore the normal balance.
He has worked with helminths for many years and discovered that they do something bacteria and viruses do not: They are potent stimulators of Th2 activity. He reasoned that people who were not infected by helminths during childhood did not experience this “Th2 conditioning” and were thus predisposed to IBD.
Testing the Theory
Experiments in animals seemed to confirm this idea. Weinstock and Dr. David Elliott of Iowa used two groups of mice, one that was genetically engineered to develop colitis and one in which colitis could be induced with chemicals. Infecting both groups of animals with worms blocked development of the disease or, if applied after the disease had begun, induced remissions.
The researchers then obtained permission from the university’s bioethics committee to use the worms to infect six people--four with Crohn’s and two with ulcerative colitis. None of the patients were responding anymore to conventional treatments.
They used a strain of helminth that does not normally infect humans. Microscopic eggs were suspended in a glass of Gatorade that the patients drank. The half-inch-long worms colonized the gut for about four to five weeks before dying off and being excreted.
“Five of the six [subjects] went into clinical remission, and the one who didn’t improved substantially,” Weinstock said, and there were no side effects. The duration of the response was from one to five months, he added, and then the symptoms slowly returned. All of the patients “vigorously requested further dosing,” he said.
Weinstock cautioned that this was a very preliminary study in a very small number of patients. “The patient wants it to work, so he may feel better even if there is no effect,” he said. To overcome this “placebo effect” problem, he is now organizing a larger study, to be conducted at several major institutions across the country, in which the patients won’t know if they received the worms or a placebo.
“We’re trying to determine if it works objectively, scientifically, appropriately and without irrational exuberance,” he said.
More information is available on the Crohn’s and Colitis Foundation’s Web site at https://www.ccfa.org and at the “virtual hospital” on the university’s Web site, https://www.uiowa.edu.
