I used to have hay fever but it was never bad enough that I resorted to ingesting worms.
In 1974, a man in his early thirties decided to run an experiment on himself. Since the age of eight he had suffered from seasonal allergies, and he was annoyed at having to take antihistamines to manage the symptoms. He thus “infested” himself, as he described it in the medical journal The Lancet, with larvae of the human hookworm, which is about 1 centimetre in length. He was hoping that the parasitic infection would essentially draw the attention of his immune system away from the grass and tree pollens he was allergic to. Over the course of the summers during which his gut served as host for these worms, he writes that he remained “completely free from all symptoms of hayfever."
It’s called helminthic therapy and its proponents are trying to hook desperate patients with parasitic worms they claim our body needs. And even though it is being taken seriously by some segments of academia, the kind of self-experimentation J.A. Turton performed on himself in the 1970s is still happening.
Are we too clean?
Deliberately infecting yourself with parasites appears imbecilic on its surface. After all, we fund programs to deworm people in the Global South because worms can cause disease. We are not talking about earthworms, here, but helminths, tiny worms that have evolved to survive inside of a host—either us or some other animal, which suffers the consequences while the worm thrives. A helminth infection can lead to anemia, hypertension, malnutrition, and gut issues. But worms are not necessarily bad, and here is where we arrive at the crux of the argument in their favour: the hygiene hypothesis.
In a nutshell, our industrialized world is too clean. Through vaccination, pasteurization, cold chain, and overall cleaning and disinfection practices, we have kept many microorganisms at bay. Meanwhile, we have seen a pronounced rise in diseases with ties to our immune system: allergies, asthma, various skin conditions, type 1 diabetes, lupus, Crohn’s disease, ulcerative colitis, and rheumatoid arthritis. Many of these are autoimmune conditions where our immune system rebels against a molecule that belongs to our body, like an army attacking its own citizens. Better diagnosis and increased medical access help explain why some of these diseases are on the rise in Westernized nations, but it’s not enough.
The hygiene hypothesis states that increased sanitation caused this rise, or is at the very least one important cause of it. Up until recently, the human race was full of parasites. It was the norm, and we contracted them through farming, hunting, working the land, eating tainted food, and drinking polluted water. This means that our immune system evolved inside bodies that were infected by helminths. The theory goes that, when you remove the worm—a so-called “old friend” of the human body—the immune system is out of balance. It malfunctions. (This theory is a bit too neat: many pieces of evidence contradict or bring nuance to it, as Dr. Christopher Labos and I discussed here.)
Scientists have tried to explain how mechanistically this would happen. An early theory centred on two types of immune response, the Th1 response versus the Th2 response. Worms were thought to provoke a Th2 response and to block the Th1 arm of the immune system. Get rid of the worms and the immune system produces a Th1 response that leads to autoimmune diseases. This yin-yang hypothesis, however, proved to be simplistic, as many of our body’s immunological weapons don’t fall neatly into either Th1 or Th2. A better understanding of immunity has led scientists to consider how worms affect specific types of white blood cells, like regulatory T cells, dendritic cells, and macrophages. I am reminded of Ed Yong’s eye-opening article appropriately titled, “Immunology is where intuition goes to die.” If it sounds simple, it’s probably not how the immune system works.
The goal of helminthic therapy is to reintroduce the worm into the body in an attempt to treat allergies or an autoimmune condition. Not all helminths are created equal, though; the ideal worm would not cause any disease, would not multiply inside the body or colonize multiple organs. It wouldn’t spread to other people or cause symptoms in its host. It would resist common medications but be killed with antiparasitic drugs. Finding such a hero worm has not been easy, but a few candidates have made it to the top of the list.
The two biggest players in this field are the human hookworm (Necator americanus) and the eggs of the porcine whipworm (Trichuris suis ova), with the latter receiving approval by the U.S. Food and Drug Administration to be used in human research. The evidence for helminthic therapy in animal models—meaning rats and mice which are bred to express diseases similar to the ones we want to treat in humans—has been encouraging, often because scientists use a lot of worms to create an effect on the immune system. The problem is that we are not large mice.
Of worms and men
Clinical studies are conducted in humans, and the few clinical trials of helminthic therapy that have been done have shown contradictory results. Sometimes, it works; sometimes, it doesn’t. The studies are small, and proponents of the technique are quick to point to issues with the negative trials: the patients had severe symptoms and had failed to respond to any treatment, so we shouldn’t generalize, and the measurements done to document improvement may not be accurate. And when researchers try to condense our findings on the topic, they will often compare a study done using one type of worm with a study done using an entirely different species, akin to comparing wormy apples to oranges.
I searched ClinicalTrials.gov, the online database of clinical research studies, and did not find any registered trial of worm therapy currently enrolling participants. Since research is so thin, people are turning to support groups to hack their immune system back to health.
A 2020 paper from a team of researchers in Canada looked at people with multiple sclerosis who sought relief by ingesting worms. Many of them felt that conventional treatments had failed them, so they turned to the Internet. The information they found was all over the place, with one source being quoted as writing, “its results are unequivocal and stunning: helminthic therapy will slow or arrest the course of relapsing-remitting multiple sclerosis in everyone who tries it.” I’m not sure that a single drug could be accurately framed in this way, much less parasitic worms.
So, desperate patients pay large sums of money to buy helminths online, often withholding the information from their doctor, whom they fear will judge them, and from their friends, who are terrified of becoming infected as a result. There are no standard protocols: many of these worms die inside the body and a new dose has to be taken. How much? How often? These questions have not been answered by researchers, so self-experimenters rely on shared anecdotes on Internet forums.
Of course, whenever fringe therapies exist, they must necessarily be sold to parents of autistic children, and here too we see anguished parents going to quack doctors who will administer worms and chelation therapy. You’d also expect helminths to make their way into the weight-loss space—pop a few worm eggs and watch the snake-like creatures ingest your excess calories—but this claim seems to be more legend than fact. If the idea of a tapeworm diet tempts you, remember that these flat helminths can burrow through your gut and infect other organs, including your brain. Fat load of good they will do you.
As for the overall safety of swallowing more benign parasites to cure yourself of an immune-related illness, like allergies or Crohn’s disease, a giant question mark remains there too. We are not pigs, so the porcine whipworm can’t infect us beyond simply living inside us for a little bit of time and catching the eye of our immune system. Yet, worms can cause internal tissue damage when they migrate from one organ to another, and they can carry bacteria and the toxins they produce if they are not tested for those before use. Human trials typically report good tolerance and no excess of side effects compared to placebo arms, but the studies are too short and too scarce to be completely reassuring.
It’s hard to predict which immune-related disease will be shown to benefit from helminthic therapy, if any. It’s not unusual for a potential therapeutic avenue to lead to a dead end or to a single proven application. With worms, any effective use will depend on demonstrating which species works, in what dose, and for how long. But the problem with these worms is that they may be too crude, too dangerous, and too “icky” to be useful, which is why scientists are trying to turn them into more manageable biopharmaceuticals.
Just like it’s the key that’s important in unlocking a door, not the person holding it, the entirety of the worm may not be necessary. So much of our immune system works by one thing binding to another and eliciting a reaction. We may be able to isolate a molecule produced by the worm that is key to rebalancing our immune system. One of the best studied ones is the sugar-protein molecule called ES-62, which is secreted by the rodent-infecting worm Acanthocheilonema viteae. It seems to protect mice against asthma, rheumatoid arthritis, and lung fibrosis, but more studies, as they say, are desperately needed.
While the alternative medicine crowd may prefer that the pharmaceutical industry not get involved in helminthic therapy, the thing is that it might ease its access. For now, these companies are unwilling to invest in therapeutic worms, since isolating them from the gut of animals risks bacterial contamination and since prospective customers are generally turned off at the idea of swallowing worm eggs. But if a molecular extract could be patented and delivered in pill form, it would be more easily commercialized.
Parasitic worms can harm us but they have been with us as our immune system evolved. Maybe we’ll find a safe way to recouple them to our immunity with proven benefits, something beyond snake oil. They might just wiggle out of the world of self-experiments and worm their way into modern medicine. We’ll just have to see.
Take-home message:
- Helminthic therapy is the voluntary infection of your gut by a parasitic worm in an effort to treat a disease related to your immune system, like asthma or lupus
- It is based on the theory that the human immune system evolved at a time when every human was infected with worms, and that increased sanitation is causing autoimmune diseases
- Studies of helminthic therapy done in animals look promising, but the few trials done in humans have contradictory results, with no application having been approved yet
- Scientists are now testing molecules made by the worms to see if they could be beneficial to people with autoimmune conditions while avoiding the risks and ickiness of ingesting worm eggs
