Why Alex infected himself with blood-sucking hookworms, and kept them

Seconds after the worms are applied to your forearm, they begin to burrow. The larvae deploy skin-dissolving enzymes and wriggle into the body to find a blood vessel. The feeling is not painful but can be intensely itchy. Once in the bloodstream, they are swept to your heart and pumped to the lungs, where they bust out of capillaries and crawl up your throat. Soon, you’ll swallow, shepherding the worms to the promised land: your guts. Here the worms affix to the walls of your intestines like leeches so they can drink your blood.

This is a highly sought-after experience. Scientists have long investigated how infection with parasites such as the human hookworm, Necator americanus, may soothe symptoms from a raft of conditions, including allergies, hay fever, asthma and multiple sclerosis. The approach, called helminth therapy, hinges on the anti-inflammatory effect of the worms, which secrete a cocktail of proteins that soothes the immune system to cloak the worm from attack.

“We are at a very exciting point scientifically,” says Dr Sheila Donnelly, a helminth (worm) researcher at the University of Galway with research links to the University of Technology Sydney.

“There is now a strong body of preclinical evidence that helminths produce molecules with powerful effects on inflammation and immune regulation.”

Despite anecdotal success stories and promising small experiments, much of the evidence from larger-scale studies into whether hookworms help with allergies, inflammatory bowel disease and insulin resistance is inconclusive or mixed.

But one thing remains consistent. At the end of these trials, researchers offer participants a deworming tablet. The vast majority refuse to take it. For some, it’s because they feel better physically and even mentally. Others, even if the worms didn’t alleviate their symptoms, find the worms inoffensive and see no harm in keeping them.

After a time, hookworm researcher and director of the Australian Institute of Tropical Health and Medicine Professor Alex Loukas said: “People think of the worms as part of their family.”

Some years ago, Loukas, who had spent years telling trial participants the worms were safe and well-tolerated by the body, decided to put his money where his mouth was.

“When I turned 50 I started to just get some general aches and pains in my knuckles, in my fingers – just general osteoarthritis, probably. And I thought, ‘oh, I wonder if the worms will help with that’.”

A colleague applied the larvae in a drop of water to his skin.

“I can’t rule out the power of placebo but, sure enough, that pain went away.”

Big families, fewer allergies

In 1989, British epidemiologist Professor David Strachan observed children from larger families were less likely to develop hay fever. Kids with many siblings frequently infected each other with microbes, viruses and parasites, he proposed, possibly improving their immune systems and protecting against allergies. Children from big farming families, with greater exposure to animals and dirt, were six times less likely to have hay fever than city kids. Strachan popularised the “hygiene hypothesis”: the idea modern sanitation and cleanliness had driven a spike in allergies in wealthy, urban societies.

That developed into the “old friends” hypothesis, which similarly argued that low-grade exposure to the microbes and parasites we’ve co-evolved with for millennia helps regulate the immune system. In the developing world, scientists were also noticing people in tropical countries with bad sanitation and high prevalence of hookworms suffered less from Crohn’s disease, hay fever and other autoimmune diseases. Studies, including one focused on about 1500 Vietnamese children, dewormed parts of the population and discovered removing the worms increased people’s sensitivity to skin allergens.

Scientists began running clinical trials testing the opposite: could introducing the worms to parasite-free people, inducing a more zoologically diverse gut, help treat immune disorders?

“Currently humans are the only vertebrate in which these parasites are not commonly found,” a 2024 review noted. “The remedy for allergic and auto-inflammatory diseases may be to recreate the ecosystem of the human body using helminths.”

In a 2015 study co-authored by Loukas, researchers infected 12 people with coeliac disease with 20 hookworms. By the end of the trial, eight participants were able to eat a small bowl of pasta, which normally would inflict diarrhoea, cramps and vomiting.

Loukas has video from a colonoscopy of a worm-infected coeliac patient. “It’s remarkable, you’ve got this one-centimetre-long thing sucking blood but around the worm there is zero sign of inflammation. It’s a perfectly healthy gut,” he says. “It’s almost like the human host is not recognising it at all and it’s just part of its biota.”

A larger, randomised clinical trial, which tested the hookworms against a placebo, failed to realise hopes that carrying the worms could help coeliacs introduce significant amounts of gluten to their diet (although people with the worms reported fewer symptoms when challenged with a low dose).

So goes the story with much of the clinical research into helminth therapy: larger-scale trials have struggled to replicate the success of earlier studies. Researchers have wondered whether people need to be exposed to the worms from a young age for them to be truly successful in controlling inflammatory disease.

A 2022 review weighing up the evidence for hookworms’ effect on inflammatory bowel disease (IBD) found the majority of studies reported a benefit but the biggest and best-designed experiments found no effect. Therefore, the review concluded for IBD, “it seems that there is an almost equal balance of evidence both for and against helminth therapy”.

Loukas, who has formed a company based on using proteins from the worms to treat IBD alongside Dr Paul Giacomin, acknowledges the clinical trial data is mixed. His solution? More worms.

“Typically, in the early-stage clinical trials, people were using anywhere between 10 and 30, maximum 40 worms,” he says. “People were treading carefully because this was kind of radical.”

A Dutch study, however, has shown people can tolerate up to 150 worms with no significant increase in the side effects, which in some people can include cramping and flatulence when the worms arrive in the gut.

“Particularly from mouse studies there’s a very clear correlation: the more worms you have, the more immunoregulation you experience, so the more therapeutic they’re likely to be. I think the field is now sort of crying out for a new trial with larger numbers of patients and larger worm doses.”

Clinical trials in the US with lacklustre results also used pig whipworm, which doesn’t survive as well in our bodies as the human hookworm, which can live in the gut for 10 years.

“That’s not the right worm,” Loukas says. “The right worm, and I think the field pretty much agrees, is human hookworm.”

A black market for worms

Despite the experimental status of helminth therapy, an online black market for worms has operated for years, servicing people desperate for relief from various maladies and compelled to self-infect. The Therapeutic Goods Administration has warned the practice is unapproved and unsafe.

“Whether they’ve got rheumatoid arthritis, multiple sclerosis, IBD, psoriasis, whatever, there are a lot of success stories on webpages about people who the current state-of-the-art therapies aren’t doing the trick, so they’re resorting to this,” Loukas says.

“It’s really risky. You don’t know what you’re getting from these sites. These online providers are not regulated.

“There’s another worm that looks very much like a hookworm called Strongyloides that I would never dream of infecting people with because it can replicate asexually within the body, whereas hookworm cannot.”

In any case, even proponents of helminth therapy don’t believe the worms themselves will work as an approved treatment. For one, the only way you can manufacture them is in a human body; Loukas serves as the lab’s source of larvae.

“When they need more worms I poop in a cup and bring it in and someone has to sift through it,” he says.

“That’s fine for us to generate material for small clinical trials, but if we were going to try and turn this into a scalable product … you’d need an entire suburb full of volunteers, and then a suburb full of volunteers to sift through all the shit.”

The field has moved towards identifying the molecules in the worms’ “secretome” and testing if they could be useful as therapies.

“The most exciting idea isn’t that worms themselves could become medicines, it’s that we can learn from them,” says Donnelly, the researcher from Galway. “These naturally occurring molecules they secreted have, in a sense, already been pharmacologically optimised by evolution.”

Donnelly is pursuing a family of proteins called Helminth Defence Molecules, which halted the progression of disease in mouse models of relapsing multiple sclerosis and type 1 diabetes. “The critical next question is whether those effects can be reproduced safely and meaningfully in people,” she says.

Loukas, through his spin-off Macrobiome Therapeutics, is investigating two proteins from the worm secretome as potential treatments for inflammatory bowel disease, which he admits will be a long, slow process. Last month he was awarded $2 million by the National Health and Medical Research Council, in part to create genetically engineered worms that produce therapeutic proteins.

“We have to learn how to design the next generation of drugs from that millions of years of evolution that’s gone on before us,” he says. “I’m just delighted to see things moving forward.”

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Angus Dalton is the science reporter for The Sydney Morning Herald.Connect via X or email.AdvertisementAdvertisement