91av

Editorial: “Let them eat worms“

People guzzling concoctions of worms to relieve their immune disorders are inspiring scientists to take parasite therapy seriously

THE ingredients seemed simple enough: water, sugar, salt and a smidgen of stool from a generous friend. Within a month, Sally had a dish of warm water brimming with hundreds of helminths – tiny worm-like parasites growing inside eggs from her friend’s faeces. She plucked 500 eggs onto a microscope slide and licked it clean. The parasites, she hoped, would colonise her gut, modify her immune system and cure her severe allergies.

Sally belongs to a growing community of people with immune disorders who are isolating and breeding parasitic worms for themselves, their friends and their customers. The idea is that helminths, which chemically bewitch the immune systems of their hosts in order to survive, can temper the overzealous immune system behind disorders like Crohn’s disease, ulcerative colitis and acute allergies.

This “citizen science” approach has not escaped the notice of researchers. Some are impressed enough to request permission to safely infect people in , while others strongly oppose worm therapy.

of New York University says he had always been aware of helminthic therapy, but “even though I considered it a reasonable hypothesis, I wasn’t brave enough to do that kind of stuff myself”.

That changed when a man with worms in his belly approached Loke with an intriguing proposal. In 2004, a 29-year-old man with ulcerative colitis – an immune disorder that ravages the intestines – flew from the US to Thailand to swallow 500 human whipworm eggs provided by a parasitologist. A few years later, virtually symptom-free, the man asked Loke, then at the University of California, San Francisco, to study his guts and look at what, if anything, the worms had done.

Repeated colonoscopies revealed that wherever worms had colonised the colon, the inflammation and bleeding that characterise colitis were significantly reduced or non-existent. Loke published his findings as a case study in Science Translational Medicine (). He was so impressed with the results that he is seeking funding for his own clinical trial to investigate just how helminths suppress the immune system.

“People now feel there are sufficient data to warrant further trials of therapeutic potential,” says of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. “The reason there aren’t more clinical studies isn’t so much scepticism about whether it works. It is more the huge number of hoops one needs to jump through in order to experimentally infect volunteers.”

Those many hoops may well be justified. Helminths can make people severely ill. of George Washington University in Washington DC emphasises that helminthic infection is a major health problem in developing countries and can cause severe digestive problems, anaemia and can stunt growth. “It’s like the old days of giving people malaria to treat syphilis,” he says. “It’s not something that has any place in modern medicine.”

There are other problems for those wishing to carry out clinical trials, not least that the same species does not behave in the same way in everyone. “Every autoimmune disease involves different tissues and cell populations. It’s naive to think that we will find one helminthic therapy that is a cure-all,” says of the University of Edinburgh in the UK. More worryingly, some helminths have been shown to worsen allergies and immune disorders rather than make them better (91av, 11 July 2009, p 42).

It is not hard to see why authorities are often reluctant to give researchers permission to infect people, but those behind the few clinical trials on helminthic therapy argue that they can minimise risks by controlling the number of worms each person receives. How a helminthic infection affects someone depends on the number of worms and the person’s age, health and diet. So a malnourished toddler in Somalia who is continually reinfected with huge numbers of hookworms will likely develop anaemia and developmental problems, whereas many healthy adult Americans are walking around with a few dozen hookworms or whipworms and show no symptoms of illness whatsoever.

One of the earliest helminth enthusiasts was of Tufts University in Somerville, Massachusetts, who has been studying the worms’ therapeutic potential since the early 2000s. In 2005, he published one of the few controlled clinical trials to appear in a peer-reviewed journal, giving 52 volunteers with colitis 2500 pig whipworm eggs or a placebo every two weeks for three months. Forty-five per cent of those who received whipworm eggs improved, compared with only 17 per cent who received placebo (Gastroenterology, ).

Weinstock is not the only one: in the same year, John Croese of Townsville Hospital in Douglas, Queensland, Australia, published the results of inoculating nine Crohn’s patients with hookworm. After 11 months, five were in remission (Gut, ).

Now researchers from the University of Wisconsin, Madison, and the University of Copenhagen in Denmark are to test whether helminths can help treat multiple sclerosis, in which the immune system attacks nerve cells.

But waiting for further clinical trials and regulatory approval is not an appealing option for many people living with immune disorders. Emboldened by the success stories told online (see “Citizen scientist: Hookworms changed my life”), some choose to take the risk and swallow vials of whipworm eggs or press bandages crawling with hookworm larvae against their skin. People who breed the helminths say that they screen donors for HIV and other diseases the worms could transmit, and point out that if an infection goes wrong there are powerful anthelminthic drugs that expel parasitic worms, such as albendazole.

“There is definitely growing interest in helminthic therapy in mainstream immunology,” says Loke. “But nobody in their garage can quality control parasites. The question is how will it work in a clinical setting?”

“Nobody in their garage can quality control parasites. How is it going to work clinically?”