December 17, 2010 | 10
Some of the worms and germs we’ve been warding off may actually keep us well. One solution, some scientists say, is to welcome them back
I met William Parker just two days before World Toilet Day, an international campaign to break taboos about, yes, potties. It’s a subject not many like to talk about. The cause is a critical one: access to sanitation and safe drinking water are key to preventing a host of diseases. But a growing body of research suggests there may be a dark side to clean living.
[Image: With allergies and autoimmune disorders on the rise, researchers find hope in some unlikely allies]
According to one theory, first proposed in the 1980s, the super-sanitized lifestyle of the western world may have curtailed some diseases but created new ones. The prevalence of asthma, allergies, and a number of autoimmune-related ills —from rheumatoid arthritis to Type I diabetes—has skyrocketed in recent decades, especially in wealthy countries. "Roughly 4 in 10 Americans suffer from allergies, and nearly 1 in 10 develop an autoimmune disorder," Parker said. "We generally don’t see these diseases in developing countries."
Duke immunologist William Parker is one of hundreds of scientists who are trying to figure out exactly what makes healthy immune systems tick, and why modern living has run them amok.
[Photo: William Parker, Ph.D]
"Certainly there’s a genetic connection. And there can also be environmental triggers, like viral infections or chemicals," Parker said. "But there’s something more going on."
The culprit, some scientists say, may be a lack of worms. Not the worms that dig in your garden, mind you, but the ones that dwell in your gut.
Until the last century, few people on Earth were parasite-free. For much of our evolutionary history, humans have played host to an array of wormy guests. Hookworms, roundworms, and whipworms have long made their homes in the warm wet folds of our intestines, bathed in a constant supply of food and nutrients.
Today, intestinal worms still infect more than one third of the world’s population. Parker, who grew up on a hobby farm in rural Arkansas, suspects he plays host to a few parasites of his own. "I probably have things in my gut that most people don’t, because I grew up drinking creek water," Parker said.
Many intestinal parasites are passed from person to person when microscopic amounts of human feces get on our fingers, or when we walk barefoot on contaminated soil. Sewage treatment and running water prevent parasites from passing from one person to the next, Parker explains. But it wasn’t always this way.
"We seem to have forgotten that it was only very recently, less than 100 year ago, that our grandparents first acquired indoor plumbing and access to modern medicine," Parker said. "A number of different worms used to live in our guts, but they’ve been wiped out."
Too clean for our own good
Parker and other scientists suspect we may be paying a price for our parasite-free existence. To find out, Parker’s research revolves around another set of animals scrubbed squeaky clean by modern living: lab rats.
Scientists started breeding strains of rodents for laboratory experiments about 150 years ago, Parker says.
"We treat them with anti-parasitic drugs, and we make sure they have clean drinking water. So in a real sense we’ve done the same things to our lab animals that we’ve inadvertently done to ourselves."
In the mid 2000’s, Parker began catching wild rats in and around Durham, NC, and comparing them to rats raised in the lab.
Parker showed me his trapping technique, learned from catching rats in his parents’ barn as a child. It’s not glamorous work. In urban areas, wild rats are lured by garbage cans and dog food bins. Parker finds rat-infested areas and sets out his traps: wire cages the size of a shoebox, outfitted with trap doors and triggers.
After putting out unarmed live traps for several days to put the beady-eyed pests at ease, he baits each trap and sets the trigger, returning later to collect his prey.
"Wild rats aren’t as friendly as the lab rats are," Parker said.
[Image: Photo of wild rat.]
Unlike sterile lab rats, wild rats are riddled with parasites — not just worms, but bacteria and viruses, lice and mites — which their immune systems have to contend with.
When Parker compared immune reactions in spleen cells of wild rats with their squeaky clean cousins, the lab rats were hypersensitive compared to their wild counterparts.
This hypersensitivity could also explain what happens when people go parasite free, Parker explained.
To evade eviction, worms secrete chemicals that quiet the bodies’ natural defenses just enough to allow them to avoid attack without harming their host.
Over millions of years of co-existence, the theory goes, our immune systems learned to tolerate these live-in guests —or "helminthes," as Parker prefers to call them —and eventually came to depend on worms to work properly.
"Ancient adaptations to deal with helminth infection may have left their mark on the way the immune system is structured and controlled," wrote Janette Bradley and co-authors at the University of Nottingham, in a 2009 article published in Immunology.
With parasites out of the picture, the body’s natural defenses go into overdrive. Our immune systems are now mounting the alarm for harmless substances from dust mites to cat dander. In the case of autoimmune disorders such as Crohn’s disease and Type I diabetes, the body’s immune system attacks the very thing it was meant to protect: our own tissues.
"Our immune system doesn’t have enough to do," so it gets bored and looks for something to fight, Parker explained. "It may be that our immune system needs the chemicals helminthes produce to function normally," he added.
Blurring the line between friend and foe
What to do? Some scientists propose a solution that’s not for the squeamish. If eliminating parasites triggered the rise in allergies and autoimmune disorders, could reuniting with the worms within restore our health?
A growing number of studies suggest that for off-kilter immune systems, a dose of gut worms may be just what the doctor ordered. Lab rodents were the first trial subjects to test the idea, but studies in humans have backed up the hunch.
Researchers at the University of Iowa are treating patients with inflammatory bowel disease (IBD) with "cocktails" laced with microscopic whipworm eggs. It may sound like a witch’s brew, but for some patients with IBD — a painful disorder characterized by diarrhea, bleeding and fever — it’s a worthwhile tradeoff. The patients had tried multiple treatments to relieve their symptoms, but nothing worked. After 24 weeks of worm therapy, 23 of the 29 volunteers went into remission.
[Photo of whipworm eggs.]
Worm therapy has also proven effective for other diseases. Multiple sclerosis (MS) is a debilitating disease in which the body attacks its own nerve cells. Scientists in Argentina followed several hundred multiple sclerosis patients for 4 to 6 years, a dozen of whom accidentally developed intestinal parasites during the study. When they compared the patients who developed intestinal parasites with the patients who remained parasite-free, the worm-infected patients had fewer flare-ups over time.
A new spin on health care
These scientists aren’t suggesting we relinquish the loo. Dozens of communicable diseases, from cholera to typhoid, travel from person to person in human feces. Waste disposal and treatment mean the difference between life and death in some parts of the world, where defecating in the open is a leading cause of contaminated drinking water.
"Nobody’s suggesting we go back to the Stone Age," Parker said.
Instead, Parker imagines a future where worm therapy is a routine part of medical care. "You would go to the doctor to get exactly the type and number of worms you needed," Parker explained. "You would get your worm levels checked just like you get your cholesterol levels checked."
Parker acknowledges this is a big shift for doctors, who are normally in the business of preventing infection. "We usually think it’s not healthy to have worms. And indeed, people already plagued by anemia or malnutrition can get sick from them," he acknowledged. But in controlled doses under medical supervision, Parker says, the parasites are unlikely to cause problems. "The risks are small compared to the potential benefits," he explained.
Why not identify the mystery compounds the worms secrete, and develop a drug that mimics their effects? When I asked Parker this question, he was skeptical. "Each worm constantly secretes dozens if not hundreds of different molecules as it travels through the body. That’s hard to reproduce with a drug."
With FDA approval for many kinds of worm therapy still a long ways off, some people are taking their health in their own hands and deliberately infecting themselves with worms in the hopes of relieving their symptoms.
But until we have a better understanding of how worm therapy works, Parker cautions, self-treatment is still a gamble.
"We still don’t know which species of worms you need, or how many, or what the timing of treatment needs to be to make your immune system stable," Parker said.
"Some of these diseases are very early onset. Which diseases can be treated after symptoms have already developed? And which diseases can be prevented, but not cured?"
With the sun setting fast, Parker loads the last of his traps, and hands me a peanut. It’s a deadly allergen to some people, but irresistible to rodents. I debate whether to wash my hands, then I take the bait.
Devalapalli, A., et al. 2006. Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis. Scandinavian Journal of Immunology 64: 125-136.
Elliott, D., et al. 2005. Helminths and the modulation of mucosal inflammation. Current Opinion in Gastroenterology 21: 51-58.
Hewitsona, J., J. Graingera and R. Maizels. 2009. Helminth immunoregulation: The role of parasite secreted proteins in modulating host immunity. Molecular and Biochemical Parasitology 167 (1): 1–11.
Jackson J., I. Friberg, S. Little, J. Bradley. 2009. Immunity against helminthes and immunological phenomena in modern human populations: coevolutionary legacies? Immunology 126: 18–27.
Lesher, A., B. Li, P. Whitt, N. Newton, A. Devalapalli, K. Shieh, J. Solow, W. Parker. 2006. Increased IL-4 production and attenuated proliferative and proinflammatory responses of splenocytes from wild-caught rats (Rattus norvegicus). Immunol. and Cell Bio. 84: 374-382.
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(1) Photo of hookworm posted to Wikimedia Commons by Jasper Lawrence (Creative Commons license).
(2) Photo by Duke Medicine.
(3) Photo of wild rat from Wikimedia Commons (public domain).
(4) Photo of whipworm eggs from Wikimedia Commons. Provided by the Centers for Disease Control (public domain).
About The Author: Robin Smith taught writing at Duke University for four years before joining the news room at the National Evolutionary Synthesis Center, where she writes about life in the deep sea, atop the world’s highest mountains, and everywhere in between. Robin has a PhD in evolutionary biology, and has published academic articles in Evolution, American Naturalist, and the American Journal of Botany. She has also written for the Raleigh News and Observer, the Charlotte Observer, and for Scitable, an online learning initiative from the publishers of Nature. Robin is a member of the National Association of Science Writers, and serves on the board of the science writers group, Science Communicators of North Carolina. When she’s not at her desk, Robin spends her time dancing, hiking, and learning the secrets of homemade sorbet. She tweets at @NESCent and (more rarely) @robinannsmith. Photo by Jon Gardiner.
The views expressed are those of the author and are not necessarily those of Scientific American.
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