At the core of the concept of the therapeutic use of infectious organisms is the idea that all complex organisms function as ecosystems. Every large multi-celled organism is dependent to a very large degree upon other organisms that use its body as their "home". This dependency is not trivial, we depend upon microbes to function. Not just to function properly, but to function at all.
To help see the human body as an ecosystem, which is a radical departure, it helps to know that 60% of your feces by weight is bacteria. That if you were to eradicate the bacteria living in your intestine you would soon die of malnutrition. That the intestine is the location of, by some estimates, 60% of our immune system. That, strictly speaking, the intestines are the surface of our exterior, a wet, semipermeable skin, in contact with the outside as we push things from the outside through a long thin hole through our bodies. That over 80% of the cells by number in and on (see above) your body right now are not human cells (they are much, much smaller than human cells).
We are a walking rain forest in a sense, and we function like one.
It is estimated that as many as 70% of species are symbionts (parasitic), most of them either have a mutually beneficial relationship with their host or one organism benefits without the other being harmed. Proper immune function is a benefit, so that some organisms currently classified as parasites of man, like most helminths, perhaps should more properly be classified as mutualistic symbionts. Although this might appear to appear to be semantics, it is important because the word "parasite" is freighted with strongly negative, and undeserved in this context, meaning.
The important take-away is that whether or not you are aware of it you depend for your very life on organisms almost universally regarded as repulsive, repugnant and that exist on and within you in enormous numbers.
Nor is the idea of a connection between infectious diseases and autoimmunity a new one. In the mid 1960s scientists made the observation that MS was more common in those who had had very clean childhoods. In 1986 Godfrey published in the Lancet what would become known as the hygiene hypothesis, based on his observation that allergies were less common in later siblings in large families. He reasoned that their increased exposure to infectious organisms throughout their childhoods via their elder, numerous, siblings was the cause.
Since then hundreds of scientific papers have been published looking at this issue and the majority confirm or extend his ideas. The result had been to refine and expand the Hygiene Hypothesis is to produce the Old Friends Hypothesis (OFH).
The OFH suggests that the immune response to infection, particularly by large multi-celled and complex organisms like helminths, is effective in moderating immune response in large measure because we and our immune systems (and by we I mean all large complex organisms) have co-evolved with every organism that has parasitized or infected us long term. Our immune systems depend upon cues provided by infection with bacteria, viruses, protozoa and helminths, to develop and function properly. To be able to properly identify appropriate targets the immune system has to be exposed to them. Since the targets must exist, according to the genetic script of the immune system - they always have existed therefore they must be here, in the absence of those targets the immune system attacks the closest analogs to the organisms we co-evolved with: pollen, dander, food, self.
Having evolved in an environment where we lived in close contact with the soil, as humans and prehumans, our bodies account for the presence of these organisms from an early age. The absence of what were universal effects and cues is the cause, according to the OFH, of many if not all of the "modern" diseases that involve inflammation or immune dysregulation. Our immune systems depends upon regular and continuous exposure to a library of organisms to develop and function properly.
Note: Autoimmunity is often used mistakenly to refer to any immunological disorder. It is a specific type of immunological disorder where the immune system identifies self tissues as foreign and attacks them. Asthma, amongst many, is by this definition not an autoimmune disorder because the body does not attack self tissues. In asthma, and most diseases of immune dysregulation, of which autoimmunity is a minority subgroup, the disease arises out of collateral tissue damage caused when the immune system mistakenly attacks benign pathogens, like cat dander or pollen.
The OFH makes sense because, as is demonstrated in the less developed regions of the world now, our bodies were home to large numbers and varieties of parasites and cohabiting organisms from within a few months of birth to death. This situation prevailed for our genes for as long as parasites and infectious organisms have existed. Much of our genetic material is ancient, predating primates or mammals, so the genetic pressure exerted on our genes by parasites predates the arrival of the particular configuration of genes that constitute homo sapiens.
Many organisms that infect or parasitize us manipulate our immune system, including bacteria. So the collective cumulative evolutionary effect of all these organisms over millions of years, even if the individual effect is mild, must be enormous.
To see the impact and the genetic bargain struck by our genes look to areas of high cholera, tuberculosis and malaria incidence. Where an individual inherits a gene from both parents that protects the bearer from each of these diseases the result is Cystic Fibrosis, Tay-Sachs, or Sickle Cell Anemia respectively. To believe that these are the only genetic consequences of coevolution with disease causing organisms or parasites is prima facie absurd. They are just the most awful and therefor apparent.
Helminthic therapy is a subset of what will one day be called something like Biological Therapy, the therapeutic, or prophylactic, use of benign infectious organisms to combat disease through deliberate and repeated infection. The idea is an obvious consequence of epidemiological observations and laboratory studies demonstrating that asthma, allergies, MS, Crohn's, UC, Lupus, heart disease, depression, etc., are unknown or almost unknown in the third world where people are commonly infected with a variety of parasites including multiple simultaneous active helminth infections. Or, in the case of multiple sclerosis that those acquiring a helminth infection after developing relapsing remitting form of the disease experience something close to remission while hosting helminths. Or that providing pig whipworm ova to thsoe suffering with IBD is as effective as prescribing Humira or Remicade. Nottingham studied Ethiopians infected with hookworm and observed that in those with hookworm asthma was 50% less likely. Many more studies than these have been performed with similar results.
To illustrate these ideas briefly consider that the first case of Crohn's disease was observed in New York City in the early 1930s, very soon after the elimination of helminths in that urban population. Or that in 1967, probably on a wheeze (ahem), an English researcher went to Ghana to look at asthma in that country. Despite staying for months he found not one case.
Consider also that there is a North-South gradient for all these diseases. The further from the equator, and the tropics, one lives the higher the incidence of <insert name of modern disease involving immune dysregulation here>. Besides a north south gradient in disease there is one for income and sanitation (as well as exposure to sunlight).
Or that within industrialized countries those living on farms or on the land experience far lower incidences of <insert name of modern disease involving immune dysregulation here>.
That babies born by Caesarian Section have higher incidences of allergies. That antibiotic use correlates with the incidence of many of these diseases.
If one examines the epidemiology of the modern diseases, like heart disease, that involve inflammation and environmental factors or triggers, even then the effect of eating too many cheeseburgers is not enough alone to explain the increase in heart disease. Some other, as yet unidentified pro-inflammatory factor is at work, which I propose is the damage done to our personal ecosystems by modern living.
That besides manipulating serotonin levels many modern antidepressants have anti-inflammatory properties for brain tissue and that inflammation has been linked to many forms of depression as a possible causative factor.
Neither genetic changes in humans (the time scale is to brief) nor environmental pollutants, nor increases in research looking at these issues are sufficient to explain the increase in these disease according to studies into each possiblity. In a matter of two or four generations we have gone from a point where Crohn's disease essentially did not exist to a point where it affects 1/250 of the population in the US. And all the modern diseases are increasing rapidly, from asthma to ulcerative colitis. Right now it is estimated that 1/85 births results in an autistic child. As recently as the 1960s arguments raged, amongst scientists and doctors although not parents, as to whether autism was a real disease or just the result of poor parenting. Now if you plan on having a child you have better than a 1% chance of having a child on the autistic spectrum. Never mind MS, allergies, asthma, Crohn's, UC, AI liver disease, Hashimoto's thyroiditis, Lupus, RA, JRA, and on and on. Most of these are diseases that were vanishingly rare or that were not observed or described until the 20th century.
Given the trend, if it continues, it is reasonable to think that within a few generations the amount of disability due to these diseases will reach a level catastrophic to our economy as resources are diverted to care for the sick. Never mind the impact on our lives. Forget Social Security, Medicaire and the baby boomers, worry about a population so sick it consumes our annual budget whole.
The immune system is extraordinarily complex and because it is a dynamic system that is hard to study is poorly understood. We have not even identified all of its constituent parts, never mind learned completely how they interact with one another or respond to pathogens. The idea that we are going to come up with such an understanding in time to create medical interventions based on drugs is ridiculous. Never mind the price of such drugs or their side effects. The drugs invented so far to treat these "modern" diseases can cost enormous sums annually, up to $500,000, and can cause terrible side effects. Remicade, according to one account I have read, is the most lethal drug on the market when one excludes accidental overdoses. Besides all this many of these drugs only effective for limited periods of time, patients develop antibodies or reactions to the drugs themselves. Drugs are not an effective response, even could we afford it. Besides this we don't have the time to develop enough new drugs to treat all these diseases, even if we had the resources.
What is needed is a simple, natural approach. Do we really want to wait decades to produce very expensive, dangerous drugs when a very effective, simple, natural solution is at hand? Lets stop treating the symptoms and fix the problem: restore the ecosystem formed by our bodies to its natural state by reintroducing missing beneficial organisms.
The use of therapeutic organisms, ones with very low risk profiles, is easy to do, in theory. In practice the medical system is not designed to prevent or cure disease cheaply. A profit driven medical system is exactly that, profit driven. Resources are quite naturally directed at solutions that produce profits. There is far more money in a palliative, for instance, than in a cure.
There is research being carried out to study the impact of parasites on the human immune system and particular diseases, often funded by drug companies, in Australia, the US (multiple locations), the UK (Nottingham, London, Edinburgh) and Japan. The drug companies obviously believe these organisms are producing something that can be used to treat disease.
I believe that the main focus of this research is probably to isolate molecules (like ES-62 derived from helminths) with immune effects that can be packaged and used as drugs. These will almost always be produced, as Humira is, from genetically engineered organisms. Drug companies don't sponsor research to develop therapies to substitute for drugs.
The result will be a very expensive drug that will have to be delivered by injection at a hospital, and very bad side effects will be a likely consequence. If any effective and relatively safe drugs are produced it will take decades.
People with Crohn's, MS, asthma, Lupus, etc., don't have decades. So why not use helminths? The CDC recommends against treating light infections of hookworm and whipworm, so the CDC obviously believes that both are safe. Unlike Remicade, Humira and Tsyabri no one is going to develop multi-focal leuko encephalopathy (brain death) because of using therapeutic helminths.
I propose that instead of spending billions of dollars annually on dangerous drugs that a more natural, safe, cheap and effective approach be used. We can still use the drugs in those cases where organisms don't work. Lets give benign organisms to children as part of their well baby care as a prophylactic measure. There is plenty of evidence that if exposure is continuous through childhood and into early adulthood the benefits are permanent. For older people protocols based on mixes of benign bacteria, protozoa and helminths would largely eliminate or arrest Type I Diabetes and its variants, asthma, allergies, food intolerances, Multiple Sclerosis, Ulcerative Colitis, Autoimmune Liver disease and Crohn's, These are just the diseases that have been studied so far. Lupus and Rheumatoid arthritis both look very promising amongst many, many others.
But of course the use of infectious organisms to treat disease is not a miracle cure, this is not a revival tent meeting. The results of helminthic therapy both in the lab and in our experience while very good, certainly comparable with drugs like Humira, Remicade, Tysabri or Enbrel in terms of the proportion getting better, are no miracle. No therapy is universally successful, none are completely safe. Any time anything is ingested or introduced into the body problems will sometimes occur, although none have to date. Nor are the results uniformly revival-tent worthy, but given what we have seen this approach should be being beaten to death by medical researchers instead of this slow drip of research currently.
This is obvious from looking at the mortality statistics for the United States. Look at how many react badly to just aspirin. So I am not proposing that this approach is without risk, what I am saying is that compared to modern drugs, even OTC ones, it is very safe.
So if its so great why can't you get it from your doctor? Primarily I think because it is a new concept, helminths have only been examined relatively recently. Along with this is that the profit motive is absent, in fact most interested parties, all but patients, would lose out from the use of helminths and other organisms in this way. The drug companies depend upon chronic conditions, and palliative treatments for them, for most of their profits. Cures and vaccines do not produce income streams in the billions. Dosing someone on a monthly basis with an expensive genetically engineered drug most certainly does. Giving someone an infection using un-patenable organisms carried by a billions of people in the third world, where the modern diseases are very rare or unknown, does not.
To understand the potential loss to the drug companies from the adoption of just helminths like hookworm look at asthma drugs. The annual market for such things is enormous and from personal experience the therapeutic results very poor. Take Singulair, a drug I was prescribed and from which I derived no discernible benefit. In 2005 the sales of Singulair were $2,975,000,000.00. Almost $3 Billion dollars! Just imagine what the annual market for antihistamines like Claritin and its generic versions is. Research Claritin's efficacy compared to a placebo for an eye-opener. Now imagine the substitution of hookworm, requiring a single dose on average every five years, for all those drugs. Helminthic therapy does not look like a good deal to the drug industry, it looks like the apocalypse.
Hookworm appears based on our early results to be more effective, far cheaper, and with milder and only transient side effects, than drugs costing two or three orders of magnitude more (100 - 1000 times as expensive).
For that reason it is not in the interest of the drug companies to take the risks associated with pushing for such a huge change in the way medicine is practiced and for the change in public attitudes required for helminthic therapy's adoption. Would you be willing to undertake the public relations task of convincing the world that they should infect themselves with a parasitic worm in exchange for the complete destruction of you business?
Biological therapy is too effective, safe, and cheap in the long run, to not be adopted. The only question about biological therapy is how long will it take and how many millions of people will live lives cut short and ruined before this idea is integrated into the practice of medicine.
Whether or not that is recognized within my lifetime one day the ideas above will form the basis for a new branch of medicine and diseases like Type I diabetes, allergies, Crohn's disease, multiple sclerosis and ulcerative colitis will for the most part be a bad memory, like Polio.
The therapeutic and prophylactic use of infectious organisms to treat disease: Biological Immunotherapy.
Helminthic Therapy A site containing the full text of many of the papers cited below.
Parasitic worms and inflammatory diseases
Asthma and current intestinal parasite infection: systematic review and meta-analysis
Helminths and the modulation of mucosal inflammation
Serious events with infliximab in patients with inflammatory bowel disease: a 9-year cohort study in the Netherlands.
Progressive multifocal leucoencephalopathy in the rheumatic diseases: assessing the risks of biological immunosuppressive therapies.
Association between parasite infection and immune responses in multiple sclerosis
Trichuris suis therapy in Crohn's disease
A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors
Helminths and harmony
Inhibition of Autoimmune Type 1 Diabetes by Gastrointestinal Helminth Infection
The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?