Trichuris suis ova whipworm and Necator americanus hookworm therapy
for Crohn's disease - New York Times article
http://www.nytimes.com/2008/06/29/magazine/29wwln-essay-t.html?_r=3D1&ref=
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June 29, 2008
Idea Lab
The Worm Turns
By MOISES VELASQUEZ-MANOFF
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 =93bad=94 genes would eventually explain the spike, but Weinstock
didn=92t 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=92t 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=92s typical response to invasion, the intruders calm the host
immune system. They force a peace, scientists think, to avoid eviction
and keep the host =97 their home and food source =97 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.
=93Hygiene has made our lives better,=94 says Weinstock, now at Tufts
University. =93But in the process of eliminating exposure to the 10 or
20 things that can make us sick, we=92re also eliminating exposure to
things that make us well.=94
At the time of Weinstock=92s initial musings, epidemiologists had
already dubbed this notion =93the hygiene hypothesis=94: 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=92s 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 =93inoculate=94 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 ****k.)
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=92s patients responded positively. (Crohn=92s 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=92s 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 =97
work is already under way =97 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, =93We=92re part of our
environment; we=92re not separate from it.=94 It=92s 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.
Copyright 2008 The New York Times Company
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