by Rob Dunn
Donlan and other advocates of rewilding are still waiting for permission to release elephants and cheetahs in the Great Plains. They have had a few more successes, albeit not with mammals. The Aldabran tortoise was introduced, this time by the Danish ecologist Dennis Hansen, to a penned area of the island of Mauritius, where another species of giant tortoise once lived. Hansen has found some evidence that the reintroduced tortoises may help to restore populations of native plants by dispersing their seeds. Seedlings from seeds pooped by the tortoises grow taller, have more leaves, and are less likely to be eaten than those that simply fall to the ground. Whether any penned tortoises will be released is uncertain.3 In the meantime, Weinstock and his colleagues started with an experiment on the habitats inside mice. They found that when you give mice nematode worms, you can prevent them from getting a mouse version of inflammatory bowel disease. With the mice as a wind at their sails, Joel Weinstock and his colleagues applied for permission from the University of Iowa Institutional Review Board to experimentally give human patients pig nematodes. Perhaps somewhat to their own surprise, they were approved.
In early 1999 patients with Crohn’s were brought, one by one, into a lab in Iowa. They were given a survey and a medical exam to see if they met the requirements to participate in the experiment. Some were too sick. Some were pregnant. Some were too well. In the end, twenty-nine individuals were selected for the study. They were advised of the health risks of the experiment, which were largely unknown. They all agreed to have a radical theory tested in their bodies. If Weinstock was right, they might get well. If he was wrong, they would stay sick or potentially get even sicker. Either way they were to become host, if only briefly, to worms of a species kin to those we have spent millions of dollars eradicating. The progress of man was, in their bodies, about to be reversed.
When you are well, the body can feel invisible. When you are sick, the physicality of the body and all of its organs and tissues becomes all too clear, even exaggerated. Crohn’s sufferers are reminded daily of the diverse ways in which the body, and digestion in particular, can fail. When things are working, we chew our food to break it down. We grind using our ancient teeth, teeth that arose in fish. Our tongue pushes the food down and our mouth coats it with saliva, which itself has enzymes such as amylase that help break down food. The resulting ball of slimy mash then passes through the stomach, where it is dissolved by acid and then on to the meters of the intestines, where each useful bit is absorbed into our bloodstream and from there trafficked on to our hot-firing cells. Amazingly, all of this machinery works most of the time for most of us. It works more often, in all likelihood, than any other machine you own, such as your garbage disposal or your car engine. But not for Crohn’s patients. Crohn’s patients are reminded, hourly, daily, often for their entire lives, of the limits of the body. They are reminded of the gut’s vulgar occupation and weaknesses. At least some of them are reminded so vehemently that taking a treatment of pig worms seemed no stranger than their more daily experience of the body’s uncomfortable failings.
While Weinstock’s patients were prepared for the treatments, so were the pig nematodes (whipworms, to be specific). Weinstock and colleagues had to ensure that the worms were not carrying diseases from the guts of their origin. The eggs were taken from ordinary pigs and given to germ-free pigs. Like any Thoroughbred, these special worms were then allowed to mate, in the privacy of their pigs.* Their eggs were then harvested and divided into small piles of 2,500 each. The eggs look like small brown footballs with knobs on each end. Inside each egg, a living fetal worm was curled, balled up as tightly as the patient’s hopes.
On March 14, 1999, twenty-nine patients, each of them sick and tired and worried, were given a glass of Gatorade with whipworm eggs suspended in it. The scientists added charcoal to the Gatorade to make the eggs invisible. The patients drank while watched by a study coordinator whose job it was to make sure that no one spit out their slurry. Each participant was willing to give the treatment a chance.4 They swallowed the drink willingly, wiped their mouths, and waited.
Each patient was observed carefully. The experiment had been done in a kind of minitrial the year before with six patients suffering with extreme cases of Crohn’s.5 The results of this new, larger study were unpredictable. It was hoped that the pig worms would not attach in the patients’ guts for long. They had not in the preliminary test, but the possibility couldn’t be ruled out. The worms could have had negative effects. The patients were aware of this. They could have also searched libraries for “whipworm” or “Trichuris,” and would have found a gallery of terrible beasts. Whipworms are like thin, featureless snakes. Mother whipworms produce thousands of eggs per day, each of which is, to use the euphemism, “deposited” by their host into the soil. Once in the soil, the eggs, if they do anything at all, wait. They wait to be accidentally ingested by someone else. Their improbable lineage has gone on like this for millions of years, one accident at a time. Back in the gut, the eggs hatch. The young worms crawl to the sides and find the mucosa where they complete their development and, once they reach adulthood, mate, though it was hoped this would not happen in the patients. The worms would, Weinstock thought, never mature, but instead simply evoke the desired immune response in patients.
A week went by. Two weeks went by. Each patient struggled to decide whether or not he or she was doing better. Four patients dropped out. More time passed. By week seven, some of the patients were feeling a little better, but some patients would have been feeling better anyway. At week twelve, the patients came back to the lab to be examined. Here was the test of Weinstock’s radical rewilding. Then the results came in. They were announced by the lab manager on the phone. Twenty-two of the twenty-five patients still in the study were doing better. By week twenty-four, the last week of the study, all but one patient was doing better and twenty-one patients were in remission. These individuals, who had all been sick, were better. Their bodies were healthier now that they had parasites.
There are two ways to react to Weinstock’s finding. The first is excitement. The second is concern about just why this effect occurs. Weinstock rewilded human guts and cured sick patients who had previously had little hope of getting better.6 Nor were these patients with mild cases of Crohn’s. These were the individuals whose disease had become untreatable by other means. Weinstock’s study was just the beginning. His success inspired others. It was not long before other researchers suggested that many or most, or perhaps all autoimmune and allergic diseases were the result of missing our parasites. Perhaps even depression was linked to the lack of worms, and some cancers too. On the basis of this broader conjecturing, more experiments followed. If anything, these follow-ups, each seemingly more outrageous and significant than the one before, have provided evidence that Weinstock’s underlying argument is ever more sound. When treated with worms, people with inflammatory bowel disease get better. Diabetic mice return to normal blood glucose levels.7 The progression of heart disease is slowed. Even the symptoms of multiple sclerosis improve.
The eradication of helminth parasites from the developed world has been heralded as one of the major public health success stories, a symbol of our control of nature. But in context of the work of Weinstock and others, the consequences of our “control” are far from clear. To do better again we must bring back some of the worms (not all, obviously—many species of worms do have truly bad effects), carefully, the way, once channeled, the Mississippi has been allowed to flow again down some of its old diversions. We often view ourselves as separate from nature, but here is the rub: Our cultures have changed. Our behaviors have changed. Our diets have changed. Our medicine has changed. But our bodies are the same, essentially unaltered from 6,000 generations ago, when going for a run meant chasing after a wounded animal or fleeing a healthy one, water was drank out of cupped hands, and the sky still cracked wide open to reveal millions of stars, white dots as unexplainable as existence itself. Our bodies remember who we are. They re
spond as they have long responded, unaware that anything has changed, as anachronistically as the pronghorn’s running or the megafauna’s fat fruits.
Yet, as Rick Bass wrote in the foreword to one of John Byers’s books about the pronghorn, “Almost never does one discovery tie things up neatly; rather it illuminates more unexplored territory and more unexamined patterns, one answer giving birth in that manner to a hundred more questions.” The first of those hundred questions was simple: Why? Knowing that our bodies seem, in some real way, to need tapeworms, whipworms, hookworms, or the like does not really answer the simplest question: Why? Take the worms out and we get sick. Put them back and we get better. We could just go on putting them back and feeling, if besieged, also better. But before we intentionally add back to our bodies what we have long thought of as an adversary, it seems worthwhile to know what on earth (or rather, “in body”) is going on. Whatever it is, it is happening to you right now, unless you already have a worm.
With time, Weinstock came to believe that the immune system requires the presence of worms to develop. Without worms, the immune system is like a plant left to grow in zero gravity. Long ago, in the evolution of land plants, conquering gravity’s consequences was a major step in the plants’ transition from swamp to land. Thick cells and strong—even woody—stems all evolved as means to cope with gravity, as did systems of transporting sugars, water, and gases. Nearly every difference between a tree and a swamp weed is a consequence of the greater difficulties plants face in dealing with gravity on land. In the absence of gravity, a plant’s roots and shoots grow in every direction, like Medusa’s wild hair. In a similar way, our immune system without parasites also seems to be challenged to distinguish up from down.
You may think I’m being too metaphorical. But to explain the relationship between worms and the immune system, immunologists themselves tend to turn more to metaphor and analogy than to fact. When pressed, Weinstock and others have begun to say things like, “without parasites, the immune system is in disequilibrium,” or “disharmony,” or in a more candid moment, “out of whack.” “Different” is how one immunologist characterized the immune system of people in developed countries. This is the language of uncertainty. No one knows quite what happens when we take our parasites away. Take all of our worms away entirely, and we seem to stand a greater chance of getting sick. Put some of them back and we get better, much of the time anyway.
Weinstock has an idea for a more specific answer. Others do too, but the differences among what various scientists think might be going on are often at odds and hard to reconcile. Nonetheless, for now, Weinstock’s version, a version initially offered by the immunologist Graham Rook at Cambridge University, is reasonable. That does not mean it is right, but at least given what we know today, it is possible.
Here it helps to know a little more about the human immune system. The body is a country with two immunological armed forces. One fights one kind of foe, viruses and bacteria; the other deals with another kind of foe, nematodes and other larger parasites. They work together, although the more the body’s energy is spent on one part of the immune system, the less there is available to be spent on the other. This is a crude, almost cartoonish explanation, but even this much we have known only since the early 1980s. I could give you all the names and details, the TH1s, the TH2s, and the other untranslatable words of the immunologists’ lexicon, but they serve, in this case, only to give the appearance of understanding, where we still have relatively little. So for the moment, just remember the two armed forces on different fronts, battling the inevitable enemies at our doors.
These two elements of our immune system have been in place for more than 200 million years. Sharks have them. Squirrels have them. Fish have them. Even some insects seem to have elements of them. They all have them because across the long history of animal lineages, each generation was filled with parasites, as well as bacteria and viruses. Our parasites were the ether in which our bodies made sense. The presence of these hangers-on has long been as dependable as gravity. Then it happened, the great change. Humans began to live in buildings and use toilets, and everything, in the last few generations—a second on a day clock of life’s history—changed.
For a long time, we understood the immune system, in its near totality, as comprising just two main kinds of defensive forces, one against bacteria and viruses, the other against larger parasites. But in just the last five years, a problem emerged in this story. We were missing something, another character. What, scientists wondered, happened when parasites become ensconced in the body? The immune system, it was known, eventually stopped attacking them, but why and how?
It turns out we had completely missed a key component of the immune system, the peacekeepers. When a parasite is ensconced and initial attempts to expel it are unsuccessful, what should the body do? It could fight forever. In some cases this does happen and when it does, the disease and the problems caused by the body’s immune response almost inevitably outweigh the trouble caused by the worm itself. In this context, the body may be better off giving in to the reality that the worm is present and learning to tolerate it. The answer appears to be, again and again, that if the parasite survives initially, the body learns to tolerate it. A team of peacekeeper cells calls off the antiparasite armed forces. The peacekeepers balance the response. They reserve the body’s energy to fight another day against a more beatable or virulent foe.
What Weinstock, Rook, and others think is that these newly discovered peacekeepers are, in a way, our historical solution, but also our modern problem. The peacekeepers, they imagine, get produced only when there is peace to keep. When there are no ensconced parasites, particularly early in development, the peacekeepers dither and wither. But the forces remain strong, and so without being otherwise occupied, they attack whatever seems foreign. They can sometimes be so eager to win that they fight whatever they come across. The body’s own bits and pieces begin to seem threatening. The peacekeepers that might otherwise call these increasingly indiscriminate forces back, do not. They are too weak. Unchecked, our immune system battles our bodies without end. It battles our bodies until we are sick and then sicker. Boils erupt on our skin. Our intestines become inflamed. Our lungs wheeze and collapse. It battles our bodies until there are no winners.
Weinstock thinks that when he introduced worms into patients, their bodies began to produce peacekeepers, which kept the peace by stopping the immune system from attacking the worms. Of course, just like the cheetahs that pursue pronghorn, hookworms can have costs, the most common of which is the loss of blood in severe infections and consequent anemia. But on average the costs appear minimal, both in a general sense and relative to the costs of fighting the worm forever. If the worm is well ensconced and the body continues to fight it (or them), the body wastes energy. And so it may be that the peacekeepers provide a mechanism for the gut to admit local defeat and at the same time prevent the immune system from a prolonged attack on the gut, whether a worm is present or in other situations. The peacekeepers keep the peace. The worms, in their way, trigger that peace. Maybe.
A second possibility also exists and this possibility (which is not really exclusive of the first) is my own favorite. It has long been known that worms in our guts can produce compounds that suppress the immune system, compounds that, in essence, signal, “Hey, it’s cool in here—no need to attack.” They do so by mimicking some of the body’s own compounds. Many different worms produce these compounds. It may be that our bodies evolved to depend on at least low levels of such worm-produced compounds. Here I do not mean that our bodies needed them, at least not originally, so much as that they could count on their always being there. Perhaps our bodies produce more of an immune response than is necessary because they are, in a way, “assuming” that some of their response will be dulled by the worms. No one can show that such a phenomenon is occurring, not yet, but it seems plausible.
In the meantime, the broader reality is that our immune systems appe
ar to have evolved in such a way as to function “normally” only when worms are present. Scientists other than Weinstock have called this phenomenon the hygiene hypothesis, where the idea is that clean living is bad for us because the functioning of our immune systems needs the “dirty” realities of worms and maybe even a particular microbe or two. What seems to have been missed is that it is not just our immune system that evolved to depend on the presence of other species. It is the shape of our guts, the enzymes we produce in our mouths, and even our vision, brains, and culture too. All of these parts of our lives evolved with the gravity of other species as a forgone conclusion. Then we removed or changed those species and in doing so, altered the biological gravity of our lives. As in the case of worms, it is not always clear what it is about having cleaned them away that causes us trouble, but it does seem clear that again and again it changes us, leaves us like a ballroom dancer with her arms held in position but nobody to hold.
We will return to the parts of our bodies shaped by the influence of other species, be they mutualists in our guts, mutualists in our fields, predators, or pathogens. Meanwhile, as you sit and read, something is happening in your gut; the forces are arming themselves. Whether or not you have a worm will influence just what they do (as will, almost certainly, other factors, such as the particulars of your genes). Your immune system is acting on your behalf, but without conscious control. It is acting right now, with armies of tiny structures. If your immune system has not turned on you, with allergies, diabetes, Crohn’s, or other problems, you have good luck, good genes, a good worm, or all of the above. But many of our immune systems will turn on us eventually. If yours does, the question is what you should do. Do you, could you, would you, search out a worm?
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