Parasitic medicine
Where did the idea of being treated with intestinal worms come from
Polina Loseva, N+1
A capsule with dark balls inside – this may look like a pill from the future, which helps immediately from allergies and intestinal disorders, and if you're lucky, then also from cancer, anxiety and Parkinson's disease. However, this is not about the wonders of modern biotech, but about an underground, controversial and unpleasant tool. The healing capsule contains eggs of worms, intestinal parasites. We talk about where the idea of being treated with worms came from and what keeps it afloat in the XXI century, in the world of monoclonal antibodies, synthetic antibiotics and gene therapy.
Rehabilitation
The idea of being treated with helminths (that is, intestinal worms) is much younger than other methods of unofficial medicine, like the same herbs or leeches. And all because until recently, medicine – both traditional and non–traditional - was engaged in the opposite: it drove worms out of a person. This task turned out to be difficult, but by the end of the XX century, medicines, together with the instructions of hygienists, did their job, and in developed countries the population of intestinal worms seriously declined. If in medieval Europe, up to 43 percent of the population carried ascaris alone, now, according to WHO estimates, only one in four people on the planet (25 percent) is infected with helminths, and mostly these are people from poor countries.
Every now and then, however, there are disturbing reports that there are much more parasitic worms in us than it seems. For example, 19 percent of people from different countries have recently found traces of a close acquaintance with toxocara– a parasite from the roundworm clan. And in some populations of Europeans – among residents of the south, farmers and their children – it is still possible to count up to 65 percent of helminth carriers. However, this hardly means that the diseases have remained undefeated – but rather that the parasites get to the population unevenly or do not cause severe symptoms, which allows them to remain unnoticed.
Anyway, by the 1980s, a generation of people had grown up whose childhood passed without friendship with intestinal parasites. And the doctors noticed that the old, familiar diseases in this generation were replaced by new ones that were previously considered rare. In 1989, British epidemiologist David Strachan calculated that children not only began to suffer from asthma, allergies and eczema more often – they got sick with them more often, the fewer older brothers and sisters they had. And Strachan suggested explaining this connection not at all by financial circumstances or a sense of loneliness. He suspected that the older children serve as an "unhygienic contact" for the younger ones – that is, a source of parasites. And those, in turn, strengthen the immune system of babies and make it resistant to allergies and other diseases.
This is how the incidence of infectious (A) and immune (B) diseases changed in the second half of the XX century (Jean-François Bach / New England Journal of Medicine, 2002).
This assumption was later called the "hygienic hypothesis". And although Strachan initially spoke only about viruses, other pathogens, including intestinal worms, have since been recorded in "useful infections". Moreover, it turned out that the benefits of them can be noticed not only years later, but also in real time. For example, in people infected with worms, multiple sclerosis progresses more slowly than in people with the same diagnosis and an "empty" intestine. And in an Indian tribe from Bolivia, it is easier and more often for ascaris carriers to get pregnant than for those who plan a family "without the help" of helminths.
And as the hygienic hypothesis became overgrown with evidence, more and more people appeared who were ready to take a risk and exchange one disease for another. By 2015, according to scientists, at least six or seven thousand people in the world deliberately planted parasites in themselves in order to get rid of some other diagnosis. Thanks to these people, the list of hypothetical targets for helminth therapy has been replenished with a variety of diseases – ulcerative colitis, celiac disease, asthma, and various types of allergies. And some desperate experimenters even reported that worms helped them cope with heart failure, headaches, autism and Parkinson's disease.
Resuscitation
What do all these diseases have in common? All of them are somehow connected with hypersensitivity – a situation when immune cells overreact to some substances, whether they are allergens coming from outside or the host's own cells, in which the immune system for some reason does not recognize its own. With celiac disease, gluten becomes such a target, with multiple sclerosis, myelin from the lining of nerve cells, and ulcerative colitis is caused by inflammation in the intestinal wall.
When an immune cell chooses whether it will attack a potential target – unfamiliar cells or molecules – it looks back at its surroundings. If the first encounter with the target occurs in conditions of inflammation, where the cell is bombarded with stimulating signals to attack, then it most often attacks. But if the immune cell meets a stranger for the first time in peacetime, then immunological tolerance may arise: the gendarme of immunity will add the newcomer to the list of local residents and will never attack him again.
This is what intestinal worms could be useful for. Since their survival in the intestines directly depends on how well they can negotiate with the host's immune system, they have perfectly learned how to create the illusion of peacetime. Some parasites secrete anti–inflammatory substances into the blood, under the influence of which there are more suppressor cells among the immune cells - those that inhibit the activity of all other kinds of immune troops. Therefore, a truce is declared not only by those cells that were going to attack the stranger worm, but also those that could take up arms against the allergen (with allergies) or their own neurons (with multiple sclerosis).
In addition, when the hooks and suckers of new guests dig into the intestinal walls, the cells begin to repair: they begin to divide more often and secrete more mucus, thereby renewing the inflamed tissue. Hence the possible benefits for intestinal ailments: ulcerative colitis, celiac disease and Crohn's disease.
The list of diseases that make people resort to helminths continues to expand. Apparently, this is due to the "fashion" for inflammation in modern medical science. Just as once an imbalance of fluids in the body was blamed for any ailments, and then, according to the precepts of Pasteur, they looked for a pathogen-a microbe, today they are looking for an inflammatory component in any pathology.
So, it turned out that with obesity, sluggish inflammation begins in the body – and fat cells that secrete pro-inflammatory proteins are to blame for this. The growth of tumors is also often caused by inflammation – it is it that destroys healthy tissue cells, and makes survivors divide more often than usual. And in the brain, as long as, as it was previously thought, immunity does not "finish shooting" at all, traces of battles – the so-called neuroinflammation - began to be noticed more and more often. Now it is already called one of the causes of Alzheimer's and Parkinson's diseases, and some scientists believe that it is also involved in the development of migraines, anxiety and other neuropsychiatric disorders. Is it any wonder that among the diagnoses with which people turn to "doctors"-parasites, there are epilepsy, agoraphobia and Tourette's syndrome?
Repatriation
Do not, however, think that in order to get yourself medical worms, it is enough just to forget everything that parents taught from childhood, stop washing their hands and start eating raw meat. Proponents of helminth therapy do not call for the hygienists to be thrown off the ship of history and to regain all parasites without exception. Their idea is to separate potentially useful worms from obviously harmful ones – and domesticate them.
Therefore, the treatment with helminths is based on a cunning technology of their breeding. It may not be easy. For example, the hero of The New York Times publication, who was prescribed by a Thai doctor to take the eggs of a parasitic worm, tried for a long time to "activate" them – that is, to start embryogenesis in them so that developing larvae would get into his intestines. All his attempts ended in failure until he realized that out of habit he was trying to raise them in a sterile environment – and did not replace the water with ordinary tap water.
Now these methods have already been worked out – not only by self-taught experimenters, but also by scientists who use helminths in clinical trials (against the same multiple sclerosis, celiac disease or asthma), in compliance with all laboratory standards for growing worms. And although helminth therapy has not yet been officially approved anywhere, we already have a rough idea of what it could look like.
Not all worms are taken to the "doctor". So far, four types of helminths have shown themselves: two human parasites – hookworm (Necator americanus) and whipworm (Trichuris trichiura), as well as pig whipworm (Trichuris suis) and rat tapeworm (Hymenolepis diminuta). Pig and rat worms are safer in some ways, because they are not able to reproduce in the human intestine, they only go through the larval stage of development in it. This means, on the one hand, that the patient's condition will always be easy to control, and on the other – that a person will not be able to infect others with them and cause an unplanned epidemic of helminthiasis. At the same time, the concentration of such worms in the body will constantly fall, and the patient will have to be fed with them. And it can be expensive – you can pay several thousand dollars a year for such therapy. Therefore, in some cases, scientists prefer human helminths that attach to the intestinal wall and can stay there for several years.
Whiptail eggs (Kerstin Fischer et al. / Emerging Infectious Diseases, 2018).
Dosages of therapeutic worms also need to be selected separately for each species – and monitor how well they take root inside the patient. For example, in the case of a pig whipworm, people are usually prescribed several thousand eggs every couple of weeks, and it is enough to eat only a few dozen larvae of a rat. And the range of their use may be different – some people, for example, say that the vlasoglav helps them better than hookworms.
Such treatment, of course, is fraught with a variety of side effects. And although the authors of the reviews note that no one has yet met with fatal outcomes after helminth therapy, discomfort can occur in almost every patient. Most often these are intestinal disorders, sometimes fever and headache. And those who undertake to be treated with hookworm will also have to go through skin problems – since this worm enters the human body through the integument, making its way to the intestines through other tissues. But since most of the patients who turn to such therapy have already despaired of being cured by classical methods by this point, they seem to agree to be patient. However, their sacrifices do not always pay off. There are cases when therapy did not help at all, and in the official reports on clinical trials (unlike the laudatory reviews of the patients themselves), so far we are talking only about "mitigating symptoms".
It would be possible, of course, to try to do without testing patients for strength, while preserving the potential advantages of helminth therapy – if you use not worms entirely, but molecules with which parasites suppress the activity of the immune system. Such experiments were even carried out on mouse models of multiple sclerosis, and not without success. However, scientists suspect in advance that this therapy will be even more expensive than breeding worms – since specific substances will have to be produced in huge quantities and delivered to the patient's body constantly, they will not stay in the intestine by themselves.
Restoration
Meanwhile, the list of possible applications of helminths continues to expand. Recently, two British scientists – gerontologist David Gems, known for his work on nematodes, and his colleague Bruce Zhang – suggested thinking about the possible role of worms in aging. Their reasoning is simple: since parasites theoretically help to cope with various age-related diseases (arthritis, obesity, possibly dementia), and aging can be considered the sum of age-related diseases, it means that helminths can be of use for prolonging life in general. At least in one of the experiments, this effect was obtained on mice – the helminth protein helped animals to live longer, which were fattened to obesity and thereby forced to age and die faster.
In addition, many gerontologists today believe that the aging process itself is largely associated with inflammation. For this, they even came up with a separate term – inflammaging. This is a process during which the immune system ceases to recognize its own body cells that have changed with age, and begins a sluggish war against its fellow citizens on all fronts, that is, in all organs little by little. We can say that autoimmune diseases are triggered in miniature in different parts of the body. And here, according to Gems and Zhang, worms could well act as peacemakers.
If this idea will appeal to other gerontologists, then helminth therapy can become mass – since everyone will have to face aging sooner or later. This means that everyone will have to be treated with worms. Some authors even today suggest making them part of a "modern balanced diet" – along with supplements like vitamin D and omega-3 (unsaturated fatty acids). In this case, the return of worms to people can turn into an unexpected triumph: if in the Middle Ages they were found in every second, and now they are found in every fourth, then in the future, where the prevention of aging will begin from a young age, worms can be in everyone's body, and the dictionary of biological terms can be replenished with the phrase "helminth" – by analogy with a microbiome.
However, the clinical triumph of parasitic worms can still be considered nothing more than a utopia. Despite the fact that individual groups of researchers conduct clinical trials of helminth therapy and publish their observations in reputable journals, this practice itself remains marginal and unpopular. Doctors, and sometimes the organizers of these tests themselves, do not recommend people to self-medicate with worms, and in no country in the world are such drugs approved for official use. And the results of the clinical trials themselves are contradictory – in some cases the effect is too mild to be called a "cure", and in others it is completely absent.
Nevertheless, a plot from the future, in which people's intestines and the pharmaceutical market are overwhelmed by helminths, and diseases and old age are decisively defeated, is theoretically possible. And if it seems unlikely or unnatural to you, then look at what happened to the direct neighbors of helminths in the intestine – bacteria. Just a century and a half since the beginning of the hygienists' war with microbes discovered by Pasteur, we have come to the fashion for studying the intestinal community and fecal transplants (by the way, they also try it with worms – so, the helminth eggs that the hero of The New York Times publication already mentioned by us were isolated from the intestines of a Thai girl). And today, no one is confused by the morning yogurt, stuffed with bifidobacteria and lactobacilli - representatives of the microcosm, which once seemed uniquely hostile to us.
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