Why We Get Sick (26 page)

Ragweed is, of course, not the only culprit. Allergies are also provoked by inhaling other pollens, fungal spores, animal danders, and mite feces, by skin contact with many different substances, by eating certain foods or drugs, and by injections of drugs or toxins like bee venom. A quarter of the modern American population suffers from some allergy or another. You or a relative or friend may well have sought help from an allergist. If so, you probably had skin tests to try
to identify the substance (
allergen
) that caused the allergy. Two kinds of advice were then forthcoming: avoid the allergen and relieve the symptoms with this or that anthistaminic drug.

Avoiding the allergen makes sense, but what about relieving the symptoms? We dealt with that kind of advice in discussing the treatment of infectious disease. Could taking antihistamine for your allergy be analogous to taking acetaminophen for fever or giving mice a pill to keep them from smelling cats? At the moment we know that the system that gives rise to allergy is a defense, but we do not know for sure what it is supposed to defend us against. We can be sure that the capacity for an allergic reaction is a defense against some kind of danger, or else the underlying mechanism, the immunoglobulin-E (IgE) part of the immune system, would not exist. It is perhaps conceivable that our IgE system is a remnant of a system that was useful for other species, but this is unlikely because systems of this complexity degenerate quickly if they are not maintained by natural selection and even more quickly if they cause any harm. It is much more likely that the IgE system is somehow useful.

This need not mean that every allergy attack is useful. In fact, an evolutionary view of inexpensive defensive reactions suggests that most individual instances will be harmful even though the system as a whole is adaptive. This is a manifestation of the
smoke-detector principle
. Smoke detectors are designed to warn people when a dangerous fire is in progress, but few of them ever perform this service. They hang there year after year doing nothing or only sounding an occasional false alarm from a cigar or smoky toaster. Yet the annoying false alarms, and the costs of the smoke detector and its occasional battery change, are well justified by the protection they provide against a major fire. More on this principle when we discuss anxiety in
Chapter 14
.

Your allergist probably did not give you a discussion about the utility of the IgE system and the evolution of its regulation. If you asked why you have to be allergic to cats or oysters or whatever, your allergist probably said something like “Well, as in everything else, people vary tremendously in their sensitivities to different allergens, and you happen to be excessively sensitive to something in cat dander. This excess in your sensitivity must be treated by avoiding cat dander and suppressing the defensive reaction it triggers.”

There are two serious difficulties with the excess-sensitivity theory. First, an allergy is not just a matter of degree. Allergic people
react to minute traces of their allergens, while nonallergic people have no apparent reaction to enormously greater quantities. In this respect allergy is quite different from an excess sensitivity to sunshine or motion sickness. The second difficulty
is
more serious. Allergy is not an extreme action of some normally well behaved system with an obvious function. IgE antibody seems to do almost nothing, at least in modern industrial countries, except cause allergy. It would appear that we evolved this special IgE machinery for no better reason than to punish random individuals for eating cranberries or wearing wool or inhaling during August.

Despite these problems, this explanation of allergies as a result of excess sensitivity is widely employed. For instance, a 1993
New York Times
article on asthma describes it as an excessive immunological reaction, one to be solved by finding a drug that can “interfere with the asthmatic process” by “keeping the lungs from responding to allergens in the first place.” Nowhere is the possibility considered that the lungs (or their IgE-carrying cells) may know something that we don’t. A widely used textbook of immunology describes allergy in a chapter entitled “Hypersensitivity” and also makes no effort to explain why the IgE cells exist at all.

O
n finding a complicated feature characteristic of a species or larger group, one of the first things biologists want to know is what it does. They assume that if it did not do something important it would not have been produced and maintained in evolution. A short digression offers a vivid illustration. The snouts of sharks contain a cluster of flask-shaped organs (the ampullae of Lorenzini, named for the Renaissance anatomist who first described them). These complicated structures have a rich nerve supply. For three centuries people guessed that the ampullae of Lorenzini regulated buoyancy or amplified sounds, but no serious biologist suggested that they were “just there.” The question stayed on the table until some adequate experiments finally showed that the ampullae of Lorenzini detect minute electrical stimuli, thus allowing sharks to detect muscle activity in potential prey hidden in total darkness or buried in the sand. This discovery was made only because some biologists,
habitués of the adaptationist program, assumed that the ampullae of Lorenzini must be an adaptation.

Before we discuss possible explanations for the IgE system and the allergies it causes, we need to describe the proximate mechanisms of allergy. When a foreign substance enters the body, it is taken into cells called macrophages (macro means “big” and phage means “to eat”), which process the proteins from the substance and then pass them on to white blood cells called helper T cells, which take the proteins to another kind of white cell called B cells. If the B cell happens to make antibodies to that foreign protein, it is stimulated by the T cell to divide and make those antibodies. Most often that antibody is the familiar immunoglobulin G (IgG), but, for certain substances, the B cell is instead induced to make IgE antibody, the substances that mediate allergic reactions.

There is remarkably little IgE, compared to other antibodies. It makes up only one hundred-thousandth of the total amount of antibody. The IgE antibody circulates in the blood, where about one out of one hundred to one out of four thousand molecules attaches to the membranes of still other cells called basophils (if they are in the circulation) or mast cells (if they are localized). When attached to these cells, the IgE remains for about six weeks. Despite the small amount of IgE, there will still be between 100,000 and 500,000 IgE molecules on each basophil, and, in an individual allergic to ragweed, about 10 percent of IgE may be specific to ragweed antigens.

These mast cells are primed, like mines floating in a harbor, waiting for reexposure to the allergen. When it does return and is bound by two or more IgE molecules on the surface of the mast cell, the cell pours out a cocktail of at least ten chemicals in the space of eight minutes. Some are enzymes that attack any nearby cells, some activate platelets, some attract other white cells to the site, while others may stimulate smooth muscle (causing asthma). One, histamine, causes itching and increased permeability of membranes, unpleasant effects that can be blocked by antihistaminic drugs. While the details are still being worked out, the general operations of this proximate mechanism have been known for about twenty-five years and are essentially the same in all mammals.

At this point you may be thinking: surely by now someone must have figured out what all that IgE machinery is there for! People have tried, but so far there has not been enough serious research to arrive at a generally accepted explanation. Many thoughtful researchers are
well aware that a system this sophisticated must have some useful function. “These cells are not simply troublemakers devoid of redeeming biological value,” says Stephen Galli from Harvard, who notes that the distribution of mast cells adjacent to blood vessels in the skin and respiratory tract places them “near parasites and other pathogens as well as near environmental antigens that come in contact with the skin or mucosal surfaces.” Galli does not, however, review evidence about the possible functions of the system. A new nine-hundred-page textbook on allergy devotes only one page to the problem. It notes that “Several roles for the possible beneficial effect of IgE antibody have been postulated,” including regulation of microcirculation or as a “sentinel first line of defense” against “bacterial and viral invasion” and attacking parasitic worms. It concludes, “With 25% of the population having significant allergic disease mediated by the IgE antibody, an offsetting survival advantage for the presence of IgE has been suggested.” But, like other textbooks, it never seriously tries to explain the adaptive significance of allergy.

The most widely accepted view is that the IgE system is there to fight parasitic worms. Evidence for this idea comes from the observation that substances released by worms may stimulate local IgE production and the resulting inflammation, which are interpreted as defensive activities against the worms. Further evidence comes from experimental studies of rats that developed strong IgE responses to
Schistosoma mansoni
infections. Transfer of IgE from one rat to another transfered protection against infection, while blocking the ability of IgE to recruit other cells made the rat more vulnerable to the worms. In people infected with schistosomes, 8 to 20 percent of their IgE may attack these worms, and those with a decreased ability to make IgE have more severe infections.

Worms such as schistosomes, which cause liver and kidney failure, and filaria, which cause blindness, were all substantially greater problems before the introduction of modern sanitation and vector control. If attacking worms is the only function of the IgE system, this supports the current practice of treating allergies in developed countries by inhibiting allergic symptoms because an allergic reaction to anything but a worm would be maladaptive. However, the evidence that attacking worms is the only or even a major function of the IgE system remains inconclusive, and some of it may be flawed by attempts to interpret the data in terms of the only available hypothesis. Alternative explanations for the association of IgE phenomena
with worms, such as the possibility that worms arouse IgE responses for their own benefit (by increasing the local blood supply), have been insufficiently considered.

There is, however, another possible function for the IgE system, one recently championed by Margie Profet, whom we met in our chapters on signs and symptoms and on toxins. Profet proposes that the IgE system evolved as a backup defense against toxins. As we argued in
Chapter 6
, our environment is and always has been full of toxins. Inhaled pollen, contacted leaves, and ingested plant and animal products all contain potentially harmful substances. Most of these toxins are formed by plants to protect themselves against parasites and insects or other plant-eating animals.

We have several kinds of defenses against these chemicals. First, we avoid them when we can. Also, the linings of our respiratory and digestive systems are equipped with toxin-fixing antibodies of the IgA group and with detoxification enzymes that collectively decompose broad categories of chemical structures. Mechanical defenses provided by mucous secretions and by the structure of our skin and absorptive surfaces also play a role. Toxins that bypass these initial defenses are attacked by concentrated batteries of enzymes in our liver and kidneys.

But suppose all these defenses fail, as all adaptations must sometimes. Then, according to Profet, comes the backup defense, allergy, which gets toxins out of you in a hurry. Shedding tears gets them out of the eyes. Mucous secretions and sneezing and coughing get them out of the respiratory tract. Vomiting gets them out of the stomach. Diarrhea gets them out of parts of the digestive system beyond the stomach. Allergic reactions act quickly to expel offending materials. This fits with the rapidity with which toxins can cause harm. A few mouthfuls of those beautiful foxgloves in your garden can kill you a lot faster than a phone call can summon first aid. Appropriately for Profet’s theory, the only part of our immunological system that seems to be in a great hurry is that which mediates allergy. Other aspects of allergy that she mentions in support of her theory include the propensity to be triggered by venoms and by toxins that bind permanently to body tissues, the release of anticoagulants during allergic inflammation to counteract coagulant venoms, and the apparently erratic distribution of allergies to specific substances.

At this point we pause to line up our ducks in a row so we can aim at them, even though we don’t yet have a way to shoot them. As we
have already noted, the first and most important question is, What are the normal functions of the IgE system? The second question is why some people are especially susceptible to allergies while others are not. The third question is why a susceptible person develops an allergy to one substance and not another, say, milk instead of pollen. The fourth question is why allergy rates seem to be rapidly increasing in recent years.

P
eople who are especially susceptible to allergies are said to be “atopic.” Atopy runs strongly in families. While the risk of clinically significant allergy in the general population is about 10 percent, the risk is closer to 25 percent if you have one atopic parent and 50 percent if both your parents are atopic. The responsible genes remain elusive, but a dominant gene on chromosome 11 may play a key role. If the genes that predispose to allergy are found, we will still need to find out why they exist. Do they, like the sickle-cell gene, give an advantage in certain environments or protection against certain infections? Or do they give an advantage when combined with certain other genes but a disadvantage otherwise? Or might they be “quirks” that did not cause disease until they interacted with modern environments?