wormy_intro2

Hundreds of self-experiments, tens of thousands of worms

In 1976, Jonathan Turton, a British parasitologist was suffering from allergies. Most of the time scientists suffer from maladies just like everyone else. They sniffle. They whine. They ache and curse the universe. They eat the soup that reminds them of their mothers. But sometimes this is not enough. Sometimes a scientist will wake up in the middle of the night with the nagging feeling that she or he is clever enough to do something more. This is when the scientist will start to read through published papers. The scientist will call his friends. The scientist will start to notice things others have missed. Then, every so often, far more often than you might imagine, the scientist will decide one day that he has figured it out, that he knows how to treat what ails him and, rather than wait to do experiments on mice, rather than wait for clinical trials, he does an experiment on himself. Jonathan Turton was one of these scientists and so it was that in 1976 that Jonathan Turton, mostly healthy except for some sniffles, gave himself a hookworm, perhaps to cure what ailed him, perhaps more simply to understand the worms consequences firsthand. The hookworm took up residence in his intestines and, for at least two years, Turton’s hay fever went away.

Now, thirty-nine years later, Bill Parker a scientist at Duke Medical Center, along with colleagues at the University of Central Arkansas, has just published a paper suggesting, on the basis of hundreds of other self-experiments and a review of the literature, that Turton was right. More than that, Parker and colleagues suspect that worms may hold the cure to treating (or even preventing) not only allergies but also dozens of other inflammatory diseases of modernity including not only Crohn’s disease but also Parkinson’s, multiple sclerosis, migraines, anxiety disorders, autism and some cancers, and heart disease. In this telling the parasitic worm is a magic bullet as sweeping in its medical consequences as was the discovery of antibiotics early in the last century. A living bullet.

To understand why this might be the case we need to back up tens of thousands of years. Before our ancestors settled in dense populations they lived as hunter-gatherers. Naked, they gathered fruits. They ate fistfuls of corpulent termites. Insects clung to their fur. These ancestors suffered from ubiquitous parasites and pathogens, particularly worms, of tens of species. Many of the worms colonized the bodies of our ancestors when they accidentally ingested soil contaminated with feces. Others crawled straight through their skin (and then made their way to the lungs where they were coughed up and swallowed).In these ways the lives of our ancestors were similar to every mammal species ever to have existed on Earth. Then things changed.

When our ancestors settled in more dense populations, they became subject to new kinds of pathogens.  Some pathogens came with the domestication of animals; cows and pigs gave us more than meat. Other new kinds of pathogens, pathogens that required the ability to move from one person to another in the cloud of a cough, emerged in response to our growing densities. Others still, such as Chagas disease, found us as we colonized new regions (with new pathogens). The bigger and more geographically widespread the populations of our ancestors grew, the more pathogens and parasites species found a way to live within them. By the time of the renaissance  more than two thousand, TWO THOUSAND, parasite and pathogen species were living on and in humans. Then things changed again, though only for some people.

shared_parasites_v4In the last few hundred years effective public health, medicine and hygiene freed those fortunate enough to be born in developed countries from nearly all of parasites and pathogens. While two thousand parasite and pathogen species can infect humans, the average child in, say, Toronto or London is infected with virtually none of the species. None. None. Zero. Escaped. In temperate, developed, countries we live in a world in which public health, like a sea wall, holds back a tidal wave of human eaters.

But there is more to the story because our immune systems, like those of chimpanzees and other apes (and also every one of our ancestors going back three hundred million years or more), evolved with parasites and pathogens as a conspicuous presence. In the absence of these parasites and pathogens our immune systems are overreactive. They are prepared for wars that don’t come (More than that, our immune systems may have been even more warlike in the years between our first settlements and two hundred years ago, in light of the two thousand parasite and pathogen species–even more ready for a fight, be it in our guts or our hearts). To varying extents, our bellicose immune systems, mismatched with our modern lives are responsible for Crohn’s disease, inflammatory bowel disease, multiple sclerosis, Parkinson’s,  and most of our other chronic modern disease. As I write about in The Man Who Touched His Own Heart, they are even responsible for our heart disease.

There is more to the story than this, more to it in the sense that we have also done other things that make our immune systems warlike. We eat foods that make our immune systems react. We mistreat our gut microbes. We smoke. We are chronically stressed and depleted of vitamin D. But you have a decent understanding of the situation if you imagine a town bully (your immune system) inside your body fighting enemies that never show up. The bully swings wildly. The bully swings and misses. The bully hits you.

This is where the worms come in. Over the last three hundred million years, worms have evolved to find ways to live happily inside their hosts. But hosts fight worms in the same way that the bodies of heart transplant recipients fight donor hearts. The worms are not helpless. Some worms cope by living life fast. They mate and escape before the immune system can throw them out. Others live years, or decades. Those others, the tortoises of the gut, they have evolved chemicals, compounds they produce to suppress the immune systems of their hosts. It was in this light that Turton did his self-experiment.  Turton’s thought that by inoculating himself with a hookworm that the hookworm would live in his gut and produce immunosuppressive compounds which would, in turn, suppress his immune system enough to resolve his allergies. This is, he says, just what happened. But was he right?

wild_life_of_our_bodies_dunnIn 2011, I wrote a book called The Wild Life of Our Bodies in which I told the story of the status quo in research on the health effects of parasitic worms. At the time one major experiment on the use of worms to treat Crohn’s disease had been conducted. The experiment was viewed as successful (the patients saw remission), but was short term. Another study showed that individuals with Multiple Sclerosis suffered far fewer lesions when accidentally infected with worms (clinical trials are underway). Meanwhile, scientists in Nottingham eagerly searched for the compounds present in the worms in order to turn those compounds (rather than the worms themselves) into a medical treatment. Mostly though the story of worms and health was dominated by a third endeavor, which I wrote about at length in the book, the efforts by a few individuals who had success in using worms to treat their own problems, individuals who did self-experiments. These self-experiments were becoming numerous in precise relationship to the desperateness of individuals (and families) coping with the horrible symptoms of their diseases.

bill_parkerAt the time at which I finished the book, the treatments were hopeful but complex, both in terms of our understanding of their effectiveness and the travails necessary to procure them. Then something I never anticipated happened. A researcher named Bill Parker, a man who I chronicled in my book in the context of his radical ideas about the function of the appendix (which now appear to be right), a man who is both clever and unorthodox, got up and walked from one chapter of the book into another, knocking punctuation and pagination here and there as he unraveled the narrative. Bill Parker whose day job is working on organ transplantation, Bill Parker who worked on the appendix as a wild deviation from his day job, Bill Parker started thinking about worm therapies and carried out a study that, were I rewriting my book, would make him not only the feature of a chapter on the appendix but also the conclusion to the story of humans and worms, at least as we understand it today.

Again and again Parker’s genius has proven to be his ability to pair grand ideas with collaborations perfectly suited to testing those grand ideas. When Parker came up with a new idea for the role of the appendix, he found evolutionary biologists he could work with to understand the evolutionary history of the appendix. When he had a new idea about the role of particular antibodies in the gut, he talked to immunologists. And most recently, when he wanted to explore the data embedded (but ignored) in self-experiments with worms,  he found a social scientist, Janet Wilson at the University of Central Arkansas. Together Wilson, Parker, and Parker’s team went about interviewing as many people as they could who had treated themselves or been treated with worms. Apart from assessing the value of worm treatments, this work is important to understanding the unregulated self-treatments going on. But what Parker really wanted to know about was the value.

Their approach was threefold, “First, individuals producing, selling, and/or distributing helminths (“providers”) for self-treatment with helminthic therapy were interviewed. Second, surveys were distributed through social media websites and via helminth providers for individuals self-treating with helminths. Finally, publically available information regarding self-treatment with helminths from a wide range of sources, including books, articles, films, and social media websites was compiled and evaluated.”

worms_taken

What did they find? For one, these treatments although rarely performed in a formal medical setting were often performed with the consent (at least tacit) of doctors in the U.S., which is to say both doctors and patients recognized the inability of existing treatments to deal with the range of problems being considered and the potential of worm treatments.  As evidence of this potential, the anecdotes collected by Parker and colleagues seem to support what has been shown experimentally in mice and rats and, in those few, precious, clinical trials in humans. Most of those who were self-treated with worms reported better treatment of Crohn’s disease and Inflammatory Bowel Disease than is seen with traditional treatment.  Remission of allergies and asthma was also common.

But these self-experiments offer something else, in addition to corroboration, they also suggest new hypotheses, new hypotheses nearly impossible to generate without the self-experiments. These hypotheses included the following…

  • Patients with allergies are more likely to have their allergies go away after if not constantly exposed to the allergen.
  • Worm treatment often affected cognition in beneficial ways, including effects on ” depression, migraine headaches, chronic fatigue, anxiety disorders, and bipolar disorder. Further, two anecdotes involving a positive effect on Parkinson’s disease were reported.”
  • Since essentially every helminth tried to date has proved beneficial, it could be hypothesized that a variety of helminths might work for treating inflammatory disease.”
  • “Some worms are more or differently effective than others.”
  • “The manner in which helminths are produced, packaged and shipped can have a strong impact on their effectiveness.”
  • “Humans desperately need an affordable, effective and easily obtained supply of worms for treatment and prevention.”
  • “Essentially nothing has been done by main-stream medicine to address the previous point.”

As hypotheses, these insights are key starting off points for whatever next steps might be taken in research on worms (as useful as anything produced in studies of mice or rats). As results, these insights come with caveats. The self-experiments are not controlled. Each one is an unreplicated anecdote. Doses vary. Follow-up varies. Measurements of well-being are often informal. More than this, the experimental results could be the effect of a placebo. Perhaps individuals who are treated with a worm experience placebo effects. Parker and colleagues consider a list of reasons why what they have seen is not just placebos and I find their arguments reasonable, but it is always worth remembering that the effects of placebos can be very, very strong. The gold standard in medicine would be to try to repeat these effects with a double blind study (in which a patient does not know if he or she is getting the real treatment or the placebo). That hasn’t been done here (or in any previous study). One question is what will be discovered when such studies are done. But there is another question, whether those studies will ever be done. For one, because the presence of a worm can be felt at various points by the patient, developing a placebo is more complex than just providing a pill with sugar in it. But for another, the funds invested in studies of worms as preventative medicine or treatments are few and poorly funded, five million dollars at the most (and probably considerably less than five million). Given that worms seem to have the potential to treat many of our worst modern problems, this is a problem. nih_money_figureIn this light, what Parker’s results make most clear is that we need to vastly expand the research being done on worm therapies in a clinical setting, with a focus on those worms seen to have the most benefits and no drawbacks. (As Parker and colleagues note, “The average naturally occurring helminth is by no means a desirable guest in our GI tract any more than the average wild wolf would make a good house pet. Rather, the animals that are the most advantageous with the least drawbacks must be selected and cultivated for human benefit.”). No treatment in consideration seems likely to have more sweeping consequences for the most common diseases in developed countries, chronic, inflammatory, diseases.

But the challenge in making advances  is that worms are radical as a treatment (or preventative), more radical than they might seem. The entire history of medicine has been built around killing bad species (ecological medicine). We have never taken the next step of also considering how to garden beneficial species. We are gardeners who spray pesticides but forget to plant any seeds. This means that regulatory agencies, funding agencies and doctors are ill-prepared to deal with worms. In this light, although Parker’s work provides a muddy window into the benefits of worms to human health, it is a window into a world that few are able to see at all.

Parker and colleagues detail the barriers to continued research on therapeutic worms. Some are regulatory. Others are ethical. To me, the biggest barrier though has to do with an element that is equal parts auspicious hope and challenge. Worms share a great deal with another, new medical intervention, fecal transplants. Fecal transplants have proven incredibly effective for dealing with some problems such as Clostridium dificile infections. Fecal transplants involve giving the feces of one healthy person to another not healthy, one. Fecal transplants offer hope for many sick folks, but they are  an admission of our ignorance relative to the diversity of the species that inhabit our bodies. Rather than figuring out which microbe a patient might be missing, we give them thousands of species, most of them not yet ever studied. Actually figuring out what each of these species does and which one (or which combination) is really valuable may take decades, or even centuries. Imagine getting approval for thousands of different clinical trials to see just which bacteria is the best one– you couldn’t, you shouldn’t, you won’t. Something similar emerges as a problem with worm therapies. Worms may seem simpler than the multitudes of bacteria, but this simplicity is illusory. Tens of species of worms infect humans; within these species exists poorly chronicled variety. But there is more than this, the worms that infect humans are tiny part of what is out there. When I was a graduate student at the University of Connecticut I worked the floor beneath a lab in which Janine Caira and her students study the tapeworms of sharks. Janine and her students, particularly Kirsten Jensen who is now a faculty member at the University of Kansas, have traveled the fish markets of the world searching the bodies of sharks for their worms. In doing so, they have in nearly every shark species they have examined, found new species, new genera, new families, new phyla even, of worms. To find these worms, Janine and Kirsten take risks to find tapeworms and name and understand them. When pressed, Janine and Kirsten might tell you some practical reasons for their work, but the truth is that they search for, name and study these species because they find them beautiful and fascinating. But now, as we contemplate the value of worms in medicine, this diversity they have found speaks to the diversity of potential value to all of us. Which of these thousands of species of worms is most useful, in which combination. If we could use any of these worms to help hundreds of thousands of people live healthier lives, which one would it be? First we have to study the worms, and we have only started.

Worm Diversity


What would Bill Parker and his coauthors do, what would they do if it were their own body that was ailing? They argue that the solution is not treatment with worms but instead the use of worms as part of a general health routine. As they put it, “It is readily apparent from a substantial number of anecdotes that self-treatment with helminths is effective for many people, probably even most people, in terms of alleviating a wide variety of inflammatory-related diseases.” In other words, they think we should all have worms, whatever lineage of worms ultimately proves to have the most positive and least negative impacts. They compare worms to vitamins, the analogy being that both our things that, in modern living, need to be supplemented. Our bodies, to Parker and colleagues, make sense only in light of the presence of worms. Without them, we are broken, a sentiment that echoes so strongly throughout their paper that it seems inevitable that Parker and those working with him have, as they have considered the evidence, and considered too their own lives, gone home and infected themselves.

The worms, for their part, aren’t conscious of this story. They continue to do what they have always done, hanging on to their one necessity as they did in our primate ancestors, as they did in the first mammals, as they did in the first reptiles, as they did in the first terrestrial vertebrates, as they did in some of the earliest fish. As Janine and Kirsten, these worms are beautiful in their intricacies, beautiful too in their diversity and, as Parker argues so clearly in his paper, sometimes even beautiful in their consequences, restoring the chronically ill to health with magic we are just beginning to understand.

Read more…

On “Overcoming Evolutionary Mismatch by Self-Treatment with Helminths: Current Practices and Experience” in the Journal of Evolutionary Medicine (PDF version)

On the heart and the immune system… The Man Who Touched His Own Heart
On our changing relationship with other species, including worms… The Wild Life of Our Bodies
On the quest to find and name every species on Earth… Every Living Thing

 

 

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