Scientists Look to Tapeworm for Drug Model

This may be a bit tough for the squeamish, but hang in there for a minute and you'll see how the lowly tapeworm may save consumers billions of dollars on pharmaceutical drugs in the years ahead while helping clean up the environment.

That sounds a bit grand for a parasite that thrives inside everything from rats to humans, but scientists at the University of Wisconsin in Madison have discovered that the tapeworm's ability to adapt to an extremely hostile environment may lead the way to making pharmaceutical drugs far more efficient. That would mean less drugs to do the same job, reducing cost and waste along the way.

A Worm With Grip

Tapeworms consist of a series of segments that can number in the thousands, breaking off from time to time to form new colonies, and eventually laying eggs that can make their way into the brain or the heart. It is most at home inside the small intestine of some other host.

What makes the tapeworm remarkable is its ability to remain in the intestine despite the fact that the body frequently flushes itself out through a process that cleanses the gut of harmful bacteria. Scientists have known for some time that the worm has a series of hooks and suckers to help it hang in there, but to a team of researchers at the University of Wisconsin, that explanation seemed inadequate.

It would be a little like keeping your footing on a slippery bank during a flash flood.

So John Oaks, professor of comparative bioscience and an expert on parasites, and Paul Bass, a gastrointestinal expert in the school of pharmacy, teamed up with other scientists at the university to see if they could find some other explanation for how the tapeworm works its magic. In short, they wanted to know precisely how the tapeworm hangs on inside an organ that is designed to get rid of everything else.

That "everything else," by the way, includes a huge chunk of the medications given to humans and animals. The drugs don't stay in the intestine long enough to be fully absorbed, so much of the medication simply passes through the body and enters the environment as human or animal waste. So about 50 percent of many drugs, according to Oaks, and up to 99 percent of others, never get a chance to help cure the disease they were designed to fight.

The Secret Biochemical

But the lowly tapeworm, it turns out, has the ability to turn off the flushing mechanism, thus hanging around to scarf up all those free nutrients. Oaks and Bass thought that if they could figure out how to make drugs do the same thing, the medication would have more time to be absorbed into the body. Hence less would actually be better, with fewer side effects and lower cost.

But how do you make a drug act like a tapeworm? The scientists think they have the answer.

"We've been working together now for about a dozen years, and all of a sudden, this kind of popped out," Oaks says.

Their research shows that the tapeworm Hymenolepis diminuta, a species found in rodents and commonly used for research by parasitologists, produces a number of biochemicals to help influence muscle activity in the intestines, and one of them is particularly significant. They found that one compound produced by the tapeworm, cyclic GMP, can actually slow or shut down the propulsive mechanism in the gut, allowing the worm to survive in an organ designed to flush itself out.

That single discovery could have profound implications in the years ahead. The chemical is cheap and easy to synthesize, according to Oaks. If it can be added to the skin of a capsule containing medication, it could slow down the propulsive activity until most of the drug is absorbed. The body does that on its own after a meal so the nutrients can be taken up, but between meals "a wave sweeps down the small intestine and takes all the bacteria and anything that's left in there and pushes it into the colon," Oaks says.

So a pharmaceutical drug doesn?t have much time to get its act together.

Getting Meds to Stick Around

"Most oral medications would benefit from prolonged small intestinal residence," Bass says. "Almost all drugs we take orally are absorbed from the small intestine. By prolonging the medication's residence time in that organ, we should enhance its absorption and obtain higher blood levels of the medication."

Of course, no one knows yet if this will work for humans. Much research needs to be done, including clinical trials that are not yet even scheduled. It won't be possible to test human patients with tapeworms because those parasites are so dangerous that they are eliminated immediately, but the tapeworm found in rats — the one studied by Oaks and Bass — is very similar to the worm found in humans.

And if the chemical can slow down the intestine in rats, it probably can in humans, Oaks says, because our intestines are also quite similar.

The researchers expect to work with a major pharmaceutical company to test out their findings. For trial purposes, the chemical could be added to a common drug, and patients who take the drug would be followed for some time.

A simple blood test, repeated over time, would tell if the chemical is working.

"If it is, the drug should reach the bloodstream in greater quantities," Oaks says.

Reducing Expensive Waste

Modern measuring devices called mass spectrometers can detected the tiniest bit of chemical in even a drop of blood. If they find an increasing level of the drug in the blood, then it would be working.

That would be very significant for some drugs. Fosamax, for example, is taken by many women to prevent or treat osteoporosis, according to Bass, but only about 1 percent is actually absorbed. The rest becomes very expensive waste, because patients spend more than $1 billion on the drug annually.

So 99 percent of the drug is ejected as fecal matter, joining a rising tide of pharmaceutical drugs that are released into the environment. That growing environmental threat is of grave concern to many scientists.

Maybe a slimy creature that invites itself into the bodies of others can lend us a helping hand here, so to speak.

Lee Dye’s column appears weekly on A former science writer for the Los Angeles Times, he now lives in Juneau, Alaska.