The Worms Within

[Dynamique]

eat before reading
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The Worms Within
By Robin Ann Smith
Guest Blog
Commentary invited by editors of Scientific American
December 17, 2010
https://www.scientificamerican.com/b...hin-2010-12-17

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.

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.

"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.

Old allies?

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.

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.

Off kilter

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.

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.

Gut reaction

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.

****

References:

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.

Parker, W. 2010. Reconstituting the depleted biome to
prevent immune disorders. Evolution and Medicine Review.

Summers, R., et al. 2005. Trichuris suis therapy for
active ulcerative colitis: a randomized controlled
trial. Gastroenterology 128 (4): 825-832.

Yazdanbakhsh, M., P. Kremsner, and R. van Ree. 2002.
Allergy, parasites, and the hygiene hypothesis. Science
296 (5567): 490-494.

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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