The history of helminthic therapy

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    It is now very clear that the presence of helminths in the human biome is essential for optimal health (see Humans need helminths), but industrialised societies became largely devoid of these organisms during the 20th century.

    While the loss of intestinal worms has undoubtedly relieved these populations of the health issues associated with pathogenic helminths, it has also led to inflammation-associated deficiencies in immune function that have contributed to pandemic levels of allergy, inflammation and autoimmune disease, as well as metabolic and neuropsychiatric disorders.

    After hundreds of millions of years of symbiosis between our ancestors and helminths, modern humans began to lose these organisms in the mid 19th century, but their absence wasn’t recognised as a problem until the late 20th century, and a convenient remedy only became available in the early 21st century.

    This page presents a timeline from the loss of helminths, through the subsequent recognition of a connection between helminth deficiency and disease, and on to the eventual use of re-worming as a treatment for the diseases that result from this deficiency.

    Included are details of relevant scientific developments and of the emergence of the probiotic practice of helminth replacement, also known as worm therapy and helminth therapy, as well as helminthic therapy.

    The origins of helminth deficiency in industrialised populations

    The second half of the 19th century saw the beginning of the end for many human helminths in industrialised nations.

    • The indoor flush toilet became widely adopted during this period of increasing urbanisation and industrial prosperity, coinciding with a dramatic expansion of the sewage system. These developments interrupted the life cycle of a number of human helminths.
    • In 1883, an automated shoe laster was patented that transformed shoe production and went on to cut the price of shoes by half. [1] This invention helped to interrupt another route of transmission for some helminths.
    • While the canning of food was developed from the mid-to-late 18th century onwards, [2] the range of canned food available to urban populations only increased significantly in the late 19th century. This allowed a wide range of foods to be preserved until immediately before use, mitigating against the growth of microorganisms.
    • Although the health benefits of purified drinking water became clear in the 19th century, and various countries experimented with water treatment during the early 20th century, it wasn’t until the 1940s that standards were finally put in place in the US for all municipal drinking water supplies. [3]
    • Artificial refrigeration had been introduced in the mid-1750s, but refrigerators for home use only became available from 1913, and full-size home freezers were not introduced until 1940. Frozen foods, previously a luxury item, then became commonplace, reducing yet another source of helminth exposure.
    • Anthelmintic drugs were introduced in the middle of the 20th century, with a range of new anthelmintic products being developed during the rest of that century.

    Recognition of the effects of helminth deficiency

    1932

    • The first description of regional ileitis. [4] This condition, characterised by inflammation of the terminal ileum, would later become known as Crohn’s disease. Its appearance at this time was arguably a result of the increasing loss of helminths from the human biome due to factors that include those mentioned above.

    1968

    • The first observation by a researcher of a possible relationship between a reduction in parasitic colonisation and an increased incidence of autoimmune disease. [5]

    1976

    • Research suggested that atopic disease was the price paid by some members of the white community of northern Saskatchewan for their relative freedom from helminth colonisation, as well as viral and bacterial infections. [6]

    2000

    • Publication of a groundbreaking paper linking a failure to acquire helminths to the prevalence of Crohn’s disease. [7] This paper was key in the development of the Hygiene Hypothesis.
    • The late Robert Summers (Professor Emeritus, Department of Internal Medicine at the University of Iowa) prepared a graphic illustrating the relationship between an absence of helminths and higher rates of autoimmune disorders. [8]

    The emergence and development of helminth replacement therapy

    1948

    • Publication of the first report of the clinical application of helminthic therapy, in which the hookworm, Ancylostoma duodenale, was used to successfully treat 25 patients with polycythemia, which causes an abnormally high number of red cells in the blood. [9] This study had been commenced in 1939.

    1970

    • Twelve naval officers who had suffered from hay-fever for some years were found to be free from this condition for an average of 2 years following colonisation with the large roundworm, Ascaris lumbricoides. [10]

    1976

    • A letter published in the Lancet reported that a parasitologist / immunologist who had suffered from hay-fever for 25 years was completely free from this condition following colonisation by the human hookworm, Necator americanus (NA). [11] (PDF)

    1986

    • Prof David Pritchard (School of Pharmacy, Nottingham University) published the first three of many papers generated by his investigations into the human hookworm, Necator americanus (NA), and its effects on human immunology. [12] [13] [14] While this work eventually led to trials using live NA in subjects with Crohn’s disease [15] and multiple sclerosis, [16] Pritchard’s primary interest has never been in therapy using living worms, but in identifying helminth-derived molecules that could be synthesised and utilised in the production of helminth-inspired pharmaceutical products. In Pritchard's own words to John Scott, he's in the business of seeking "drugs from bugs".

    1995

    • While looking over decades of literature as he edited journal articles on parasites of the liver and intestine, Prof Joel Weinstock from Iowa University kept coming across the idea that all well-adapted helminths perform some useful function for their hosts, if only to assure the host’s survival in order to provide them with a long-term home. [17] He said later that it was while he was sat on a delayed plane waiting for takeoff that the "Eureka moment" occurred, and he began to wonder whether the reintroduction of helminths might help his IBD patients.

    1999

    • It was reported in the New York Times that researchers at Iowa university, led by the late Prof Joel Weinstock, had used pig whipworm ova (TSO) to successfully treat six patients with acute, chronic IBD who had previously failed pharmaceutical therapies. When these subjects relapsed after the worms died, they were said to have been "begging to be re-treated”. [18]

    2002

    • A study found that intestinal nematode colonisation ameliorated experimental colitis in mice. [19]

    2003

    • A trial demonstrated that pig whipworm ova (TSO) can reduce symptoms of Crohn’s disease without producing side effects. [20]
    • The ova of the pig whipworm, Trichuris suis (TSO) were offered for sale for the first time by Ovamed, founded by Detlev Goj. After having started to develop the process for manufacturing TSO in around 1998, and carried out several years of further product development, Goj worked with the late Prof Joel Weinstock at Iowa University to carry out clinical trials to demonstrate TSO’s safety and efficacy. This led to the granting of regulatory approval by the Thai FDA for the sale of TSO in Thailand. Ovamed would be superseded in 2015 by Tanawisa, also owned by Goj.

    2006

    • A dose-ranging study explored the number of Necator americanus (NA) that would be required to have a therapeutic effect on asthma. [21]

    2007

    • Publication of the first study to explore the effects of helminth colonisation on immune response and the natural course of Relapsing Remitting Multiple Sclerosis (RRMS). This study showed that this disease progressed much more slowly in patients who hosted intestinal worms. [22] (PDF)
    • The helminth provider Autoimmune Therapies (AIT) was founded by former marketing executive, Jasper Lawrence, former medical student, Garin Aglietti, and clinical scientist, Marc Dellerba. This was the first company to sell the human hookworm, Necator americanus (NA), to the public, and its clients had to sign up for a three year contract entitling them to both NA and personal support. Initially, they also had to travel to the clinic of Dr Llamas in Mexico to collect their hookworm doses.

    2008

    • This year saw the start of an ill-conceived decade-long research programme that proved to be catastrophic for the reputation of helminthic therapy in general, and for TSO in particular.
    The results from early trials of TSO carried out in the first few years of the 21st century had been very encouraging. [23] [24] [25] [26] But a raft of twelve trials carried out by a different research team between 2008 and 2017, to investigate the effect of TSO in five different diseases, produced such universally lacklustre results that all but three of them were discontinued prematurely. [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38]
    The researchers involved in this unprecedented project made two critical errors in their study design, the first of which was to use a trial length of only 12 weeks. While this is the standard trial period used in pharmaceutical research, it is not appropriate for studies of live helminths such as TSO, which typically only begins to deliver benefits after 8 weeks, and remission only after 20 weeks, with even longer waits experienced by some patients with severe or chronic disease.
    Arguably the most critical mistake was to insist on the use of a novel TSO formulation with a pH of 5.0, even though the investigators were advised against this by the product’s manufacturer, who knew from his own product development work that TSO is most effective when formulated with a pH of 2.4, which was the formulation used in the earlier, more successful trials. [39] (No abstract | Full text PDF)
    Other significant errors in the design of these trials included the use of a single dose size for all participants, when it is known that the helminth dosage requirements of individuals can vary by as much as a factor of 10. Also there was poor subject selection, evident in the high rate of improvement in the placebo group in some cases.
    With so few clinical trials of helminthic therapy having been carried out previously, the sheer number of these “failed” studies overwhelmed the existing helminthic therapy research base to deliver a body blow to the therapy’s reputation that has set back progress by at least 20 years.
    Other researchers began referencing these trials in support of assertions that TSO is ineffective. For example, four of these trials were included in a meta-analysis of only six studies, based on which the authors concluded that TSO therapy showed no statistical benefit in IBD. [40] Apart from the issues with the product's pH, only one of the trials reviewed in this analysis had lasted for longer than 12 weeks, and the remit of that particular study was only to assess the safety and tolerability - not the efficacy - of a single dose of TSO.
    For more detail about these issues, see Problems with clinical trials using live helminths.
    • The helminth provider, Worm Therapy, was founded by Garin Aglietti, after he left Autoimmune Therapies (AIT). The new company began selling NA via a two year contract entitling clients to both worms and support.
    • The first helminthic therapy discussion group was created on Yahoo by Jasper Lawrence. This remained the go-to venue for discussion about therapy with hookworms - and, from 2009, also human whipworms - until 2010, when the first of several helminthic therapy groups was created on the Facebook platform.

    2009

    2010

    • Australian researchers Prof Alex Loukas (James Cook University) and Prof John Croese (The Prince Charles Hospital, Brisbane) began clinical trials using the human hookworm, Necator americanus (NA), in human subjects with coeliac disease, and continued with this work for a number of years. [41] [42] [43] [44] [45] [46] [47]
    • Helminths are described as one of humankind’s heirloom species. [48]
    • Ian Roberts (Professor of microbiology, Manchester university) proposed that the presence of helminths in the human gut is essential for health. He likened the situation to a three-legged stool, with the microbes, worms and immune system regulating each other in the development of a functional immune system. [49]
    • In a paper explaining why the replacement of absent "old friends" may be the only reasonable therapy for a wide range of immune-associated disorders, including allergy, autoimmunity and autism, William Parker (at that time, Associate Professor in Surgery, Duke University) asserted that living helminths are preferable to helminth-inspired drugs, [50] an idea that would be echoed many times during the following decade. [51] [52] [53] [54]
    • A paper was published providing a comprehensive cellular and molecular portrait of dynamic changes in the intestinal mucosa of an individual who infected himself with Trichuris trichiura ova (TTO) to treat his ulcerative colitis. [55] (PDF)
    • A member of the helminthic therapy community who was using the alias, Herbert Smith, set up several helminthic therapy groups on Facebook, after reaching a commission deal with Jasper Lawrence that Smith had hoped would allow him to monetise helminthic therapy. However, when Smith refused to reveal his real name to those he referred to Lawrence's company, AIT, Lawrence terminated their agreement. He also failed to pay Smith the commission he had already earned, to which Smith responded by using his Facebook groups to mount a campaign of disparagement against Lawrence and AIT, while promoting AIT’s competitor, Worm Therapy. Smith’s behaviour and overtly partisan activity continued to polarise the community around the two providers for the following two years, until Facebook discovered that “Herbert Smith” was a fake identity, and deleted the account in 2016.

    2011

    • After previously having helped the staff of AIT to moderate the Yahoo Helminthic Therapy forum, John Scott assumed ownership of the group after Jasper Lawrence lost interest in social media and had indicated that he might delete the group. Scott continued to manage this forum until Yahoo closed down its groups operation in 2020.

    2012

    • Publication of a paper summarising the science underpinning helminthic therapy. [56]
    • The Helminthic Therapy Support group was founded on Facebook by John Scott to provide support to self-treaters and focus on the therapy. The group initially had a provider-agnostic policy to prevent the divisive practices that had plagued the earlier helminthic therapy groups created on Facebook by Herbert Smith.

    2013

    • Publication of a paper explaining how the modern pandemics of autoimmune, inflammatory and allergic diseases are due to the loss of species - especially helminths - from the human ecosystem. [57]
    • In a letter to Nature, Stephen Flowers (University of Kent, UK) and Michael Hopkins (University of Sussex, UK) noted that using a pseudo-pharmaceutical process to evaluate helminthic therapy would be likely to cost millions of dollars and take more than a decade. Instead, they suggested that researchers could utilise the insights and evidence of self-treaters in a revised model that would better reflect patient behaviour and capabilities. [58]
    • The helminth provider, Biome Restoration, was founded by the late physician, Don Donahue, clinical scientist Marc Dellerba, and nutritionist and long-time advocate of helminthic therapy, Judy Chinitz. The company made HDCs - the cysticercoids of the rodent tapeworm, Hymenolepis diminuta - available commercially for the first time.

    2014

    By now, the evidence supporting helminthic therapy was so compelling that several of the researchers who had examined the effects of helminths on autoimmune disease admitted privately that, were they, or a member of their family, to develop an autoimmune disease, they would not hesitate to use one of the available therapeutic helminths. One researcher even said this publicly.
    Quotein.gif
    In developed countries, where we are well nourished, worms are potentially good... If I had Crohn’s disease, ulcerative colitis or multiple sclerosis, I would infect myself without hesitation. (Alex Loukas, Distinguished Professor, Australian Institute of Tropical Health & Medicine, in Life On Us)
    • The helminth provider, Wormswell, was founded by an anonymous microbiologist who introduced a new, more user-friendly business model by selling single doses of NA at reasonable cost using the Bitcoin cryptocurrency. The company only traded for four years, before withdrawing from the market in 2018, after other new providers had begun to offer a similar service including single doses of NA.
    • An HDC User Discussion and Support group was created on Facebook by an enthusiastic HDC user looking to share experiences with this relatively recently introduced organism, but this single-species group only ever gained a very limited membership and was eventually deleted.

    2015

    By this date, there were already many thousands of individuals self-treating with one or more of the available therapeutic helminths, and, while many doctors and medical researchers were still expressing varying degrees of disapproval for the practice, some scientists recognised the value in the self-treatment approach.
    Quotein.gif
    Although self-treatment with helminths cannot be recommended by medical professionals due to a lack of blinded, placebo controlled trials, neither should it be discouraged since the available evidence suggests that it is beneficial in most cases when practiced by knowledgeable individuals. [59]
    • The first socio-medical study to examine the methods and outcomes reported by helminthic therapy self-treaters was published, [60] and its authors concluded that,
    Quotein.gif
    What was a costly and sometimes risky venture into the unknown, undertaken by only a few 10 years ago, is rapidly becoming a readily available and well-established resource currently used by thousands of individuals.
    This socio-medical surveillance also broke new ground by revealing that helminthic therapy could be very helpful with neuropsychiatric disorders. While the link between helminth exposure and freedom from allergy had been established during the previous 50 years, this latest paper was the first to report on the beneficial effects of helminths on major depressive disorder and anxiety disorders - the most prevalent problems in Western populations apart from allergy, with a tendency to be even more debilitating than allergies.
    Quotein.gif
    This study finds that the therapy is being refined through experience and is now expanding to treat widespread neuropsychiatric problems such as depression, anxiety, migraine headaches, bipolar disorder, and perhaps Parkinson’s disease.

    2016

    • Researchers had previously demonstrated that rats infected with bacteria as newborns display life-long vulnerabilities to cognitive dysfunction. In a new study in a laboratory animal model, they confirmed that perinatal exposure to helminths prevents persistent immune sensitization and cognitive dysfunction induced by early-life infection. Their data pointed to an inter-relatedness of various components of the biome, and suggested potential mechanisms by which helminths might exert therapeutic benefits in the treatment of neuroinflammatory and cognitive disorders. [61]
    • Publication of the first study to probe the practices and experiences of helminthic therapy self-treaters, as viewed through the eyes of their physicians. [62] (PDF)
    • The helminth provider, Symmbio, was founded, initially to supply the human hookworm, Necator americanus (NA), but adding the ova of the human whipworm, Trichuris trichiura (TTO), some time later.
    • A study investigating the immunomodulatory effects of colonisation by the human whipworm, Trichuris trichiura (TTO), in a self-infected volunteer without intestinal disease, found that both regional and systemic immunity were modulated. The authors opined that immune modulation induced by helminths may have a role to play in the future treatment of autoimmune diseases. [63]
    • William Parker (Associate Professor in Surgery, Duke University) whose team in the Immune Dysfunction and Evolutionary Mismatch Laboratory was studying the practices and outcomes of the helminthic therapy self-treatment community, felt sufficiently confident about the importance of helminths to human health to make the following comment to the author of an article written about the experience of one self-treater.
    Quotein.gif
    Twenty years from now everybody is going to have a helminth, and no insurance company will begin to cover you if you don’t have your helminths ... We’re very confident in the science, that every single human being needs a helminth. It’s part of our biology. [64]

    2017

    • A paper was published noting, firstly, that the effects on the human biota caused by thousands of years of human cultural change have strongly influenced human health, and, secondly, that, while these changes have, over the past 30 years, been reflected in the evolution of the hygiene hypothesis into a nuanced biota alteration theory, the knowledge acquired during this process has been tragically under-utilised by modern medicine. [65]
    • Stephen Flowers (Professor of Management [Innovation] at the University of Kent) published a book chapter exploring the implications of innovation in the context of helminthic therapy and Crohn’s disease. [66] Although the data that Flowers referenced had been collected several years previously, in the very early days of helminthic therapy self-treatment, his commentary remains pertinent many years later.

    2018

    • The helminth provider, YourSymbionts was founded. They began by selling the human hookworm, Necator americanus (NA), and added the ova of the human whipworm, Trichuris trichiura (TTO) some time later.
    • Jamie Lorimer (Professor of Environmental Geography, Oxford University) published the first of three papers about the ecological turn underway in immunology, referencing helminthic therapy. [67] [68] [69] Focusing on the hookworm, Necator americanus (NA), and its restoration to the human biome, the first of these papers considered how probiotic approaches to the restoration of microbial life were being added to existing antimicrobial approaches, in relation to an emerging model of “post-paleo” microbiopolitics.
    • An article was published by the New Zealand Herald describing the experience of a pathologist and medical microbiologist who, having become interested in the concept of helminthic therapy, proceeded to intentionally colonise himself with the human hookworm, Necator americanus (NA) as a personal experiment. With no particular expectations of what the results might be, this doctor reported being astounded and gratified when the arthritic pain vanished from his knees, the plantar fasciitis affecting his heels completely resolved and, for the first time in his life, he was able to lose weight and keep it off. [70] Similar experiences have been reported online by many hundreds of others who have benefitted from helminth replacement. See, Helminthic therapy personal stories. And, for many more media articles, see, Helminthic therapy in the media.

    2019

    • The helminth provider, Au NAturel, was founded as a source for NA.
    • A New Zealand scientist, Prof Graham Le Gros gave a series of interviews to representatives of the media to promote his research with hookworms and the development of a hookworm vaccine, and used every one of these interviews as an opportunity to ridicule those who self-treat with helminths. [71] This not only revealed this particular scientist’s ignorance about the reality of helminthic therapy, but also illustrated how the thinking of many academics was still firmly entrenched in the increasingly outdated Pasteurian paradigm.
    • The Yahoo Helminthic Therapy forum was reduced to an email list after Yahoo removed the user content from all its groups, a step that removed 11,000 posts from the Helminthic Therapy forum alone.

    2020

    • The results were published for a randomized double-blinded placebo-controlled trial in which patients with Relapsing Remitting Multiple Sclerosis (RRMS) were colonised by hookworms. [72] Although the statistical endpoint determined by the trial’s design was not reached, the data nevertheless revealed that more than half the patients given hookworms had not developed any new lesions.
    • Jamie Lorimer (Professor of Environmental Geography, Oxford University) published the book, The Probiotic Planet: Using Life to Manage Life, which focuses on two forms of “rewilding” occurring on vastly different scales: the use of keystone species like wolves and beavers in landscape restoration, and the introduction of hookworms into human hosts to treat autoimmune disorders.
    • The Yahoo Helminthic Therapy forum was deleted, after 13 years in existence, when Yahoo finally closed down its groups operation after many years of neglecting the platform.

    2021

    • In their third socio-medical study of individuals self-treating with helminths, [73] researchers from the Immune Dysfunction and Evolutionary Mismatch Laboratory (IDEML) at Duke University opined that the disappointing results from “gold standard”, double-blind, placebo-controlled clinical trials of helminthic therapy (see the first entry for 2008, above) were likely to have been due to a lack of appropriate consideration of the biology of the organisms used, and of the nuance of their interaction with their hosts.
    The IDEML researchers drew attention to the fact that the lacklustre, and even false negative, results from clinical trials have been starkly at odds with other strands of evidence that include numerous positive results in animal models, the positive results reported for individuals self-treating with helminths [74] [75] (PDF) and the positive reports from clinical examination following accidental exposure to helminths. [76] [77] [78]
    The study’s authors suggested that, with the impetus no longer being provided by medical researchers, the community of helminth self-treaters has become the primary "laboratory” for helminthic therapy, adding that this community’s “biohacking” endeavours may yet prove to be critical for public health by addressing the helminth deficiency that is a fundamental cause of disease in Western society.

    2022

    • The helminth provider, Nathural, was founded to supply NA to Europe and the UK.

    Helminthic therapy today

    Today, there are three distinct approaches being taken to the utilisation of helminths for therapeutic purposes.

    • Firstly, medical researchers are working towards developing pharmaceutical products by identifying and synthesising molecules mined from helminth excretory/secretory products. In this approach, clinicians working within mainstream medicine will be unable to offer "helminth-derived product therapy" (HDPT) to their patients until researchers have created, and successfully trialled, helminth-inspired drugs, and these have then been granted approval by medical regulators. It will therefore be many years, if not decades, before this endeavour delivers products to the clinic, and, when it does, they may prove to have long-term adverse side effect profiles similar to many other single molecule pharmaceutical products.
    • Secondly, a novel approach to the therapeutic use of living worms is being explored by scientists investigating the custom engineering of organisms to perform specific functions, such as seeking out and destroying cancer cells, [79] or protecting soldiers from chemical and biological weapons. [80]
    • A third approach has been taken by thousands of patients, [81] along with naturopathic and functional physicians, [82] all of whom are employing one or more of four specially domesticated species of living non-pathogenic helminth to treat a wide range of immune-related disorders. [83] Numerous scientists have expressed support for this form of therapy [84], some of them arguing that biome reconstitution using living helminths will always be preferable to the use of synthesised pharmaceutical products. [85] The helminth "probiotic" approach also offers patients a self-administered treatment that is very safe, [86] remarkably effective [87] and available for immediate use [88]. Detailed information about all aspects of the therapy is available in this wiki, [89] while support is available online from knowledgeable and experienced users, [90] along with information from doctors and other health professionals who have personal experience with the therapy. [91]

    Now that helminth replacement therapy has been developed to the point it has reached today, there is no longer an excuse for any medic to disparage the practice, or to attempt to dissuade their patients from using it on a self-treatment basis, yet there are still many doctors who persist in doing this. Some even refuse to provide routine medical care to those patients who choose to host helminths to improve their health, even though this behaviour by doctors clearly violates a fundamental principle of bioethics that is taught to all healthcare students: primum non nocere (first, do no harm).

    See also

    For a general introduction to helminthic therapy, see the following page.

    The following list of 900 scientific papers encompasses the history of helminthic therapy research.

    The next two pages give more detail about specific aspects of helminthic therapy history.