Why We Get Sick (6 page)

O
ur bodies have a related defense mechanism, of which most people are unaware and which physicians sometimes unwittingly attempt to frustrate. Here are some clues about how it works. A patient with chronic tuberculosis is found to have a low level of iron in his blood. A physician concludes that correcting the anemia may increase the patient’s resistance, so she gives him an iron supplement. The patient’s infection gets worse. Another clue: Zulu men often drink beer made in iron pots and often get serious liver infections caused by an amoeba. In contrast, less than 10 percent of Masai tribesmen have amoebic infections. They are herdsmen and drink large amounts of milk. When a group of Masai were given iron supplements, 88 percent soon got an amoebic infection. In another study, well-meaning investigators gave iron to supplement the low levels found in Somali nomads. At the end of one month, 38 percent had infections versus 8 percent of those who had not taken the supplements.

Yet another clue: eggs are a rich source of nutrients, but their porous shells can be readily penetrated by bacteria. So how can eggs stay fresh so long? They contain lots of iron, but it is all in the yolk, none in the surrounding white. Egg white protein is 12 percent conalbumin, a molecule whose structure tightly binds iron and thereby withholds it from any bacteria that might get in. Prior to the antibiotic era, egg whites were used to treat infections.

The protein in human milk is 20 percent lactoferrin, another molecule designed to bind iron. Cow’s milk has only about 2 percent lactoferrin, and breast-fed babies consequently have fewer infections than those fed from bottles. Lactoferrin is also concentrated in tears and saliva and especially at wounds, where an elevated acidity makes it especially efficient in binding iron. The researchers who discovered conalbumin predicted that there should be a similar molecule to bind iron within the body. This led to the discovery of transferrin, another protein that binds iron tightly. Transferrin releases iron only to cells that carry special recognition markers. Bacteria lack the needed code and can’t get the iron. People suffering from protein deprivation may have levels of transferrin less than 10 percent of normal. If they receive iron supplements before the body has time to rebuild its supply of transferrin, free iron in the blood makes fatal infections likely—as has been a tragic outcome of some attempts to relieve victims of famine.

By now the nature of this defense is surely obvious. Iron is a crucial and scarce resource for bacteria, and their hosts have evolved a wide variety of mechanisms to keep them from getting it. In the presence of infection, the body releases a chemical called
leukocyte endogenous mediator
(LEM), which both raises body temperature and greatly decreases the availability of iron in the blood. Iron absorption by the gut is also decreased during infection. Even our food preferences change. In the midst of a bout of influenza, such iron-rich foods as ham and eggs suddenly seem disgusting; we prefer tea and toast. This is just the ticket for keeping iron away from pathogens. We tend now to think of bloodletting as an example of early medical ignorance, but perhaps, as Kluger has suggested, it did help some patients by lowering their iron levels.

It became clear in the 1970s that low iron levels associated with disease could be helpful, not harmful, but even now, Kluger and his associates find that only 11 percent of physicians and 6 percent of pharmacists know that iron supplementation may harm patients who have infections. Although the sample was small, the study illustrates the difficulty of making clinicians aware of some established scientific findings. Even top researchers may neglect to mention this adaptive mechanism. A recent study in
The New England Journal of Medicine
showed that children with cerebral malaria were more likely to recover if they were treated with a chemical that
binds iron, but the article did not describe the body’s natural system for binding iron during infection. The evolved mechanism that regulates iron binding is but one specific illustration of the broader principle that we should be careful to distinguish defenses from other manifestations of infection, slow to conclude that a bodily response is maladaptive, and cautious about overriding defensive responses. In short, we should respect the evolved wisdom of the body.

M
edical researchers are not the only ones who deal with conflicts between organisms. Ecologists and animal-behavior specialists routinely deal with predator-prey relationships, struggles between males for mating opportunities, and many other sorts of conflict. They recognize the evolutionary significance of the phenomena they observe and use such terms as
strategy
and
tactic, winner
and
loser
, and other indications of commitment to the adaptationist program. This approach has been richly rewarding for ecologists and others who are steeped in Darwinism. A similar approach to phenomena such as fever ought to be similarly rewarding in a field of such vital interest to all of us.

The contest between parasites and their hosts is a war, and every sign and symptom of infection can be understood in relation to the underlying strategies of one or the other belligerent. Some, like fever and iron withholding, benefit the host (defenses); others benefit the pathogen; and a few are incidental effects of the war between them. The strategies are not, of course, products of conscious thought, but they are strategies nonetheless. Bacteria that sneak into the body by pretending to be harmless are rather like Greek soldiers hiding in a wooden horse. When the manifestations of infection are related to conflicting interests, they fit neatly into categories based on their functional importance.
Table 3-1
gives an overview of these categories and a guide to the organization of this chapter.

T
ABLE
3-1 A C
LASSIFICATION OF
P
HENOMENA
A
SSOCIATED WITH
I
NFECTIOUS
D
ISEASE

How can a host guard against infection? First, it can avoid exposure to pathogens. Second, it can erect barriers to keep them out of the body and act quickly to defend and repair any breaches in the defenses. If pathogens do get beyond the outer ramparts, it can flag any cells that lack proof of identity and expel them from their entry portal. If they have breached this defense line, it can poke holes in them, poison them, starve them, do whatever is necessary to kill them. And if all this does not work, it can wall them off so that they cannot reproduce and spread. If they have done damage, it can repair it. If the damage can’t be repaired immediately, it can compensate for
it in some way. Some of this damage and the resulting impairment benefit neither the host nor the pathogen. They are, like the aging bomb craters on the coast of France, just incidental relics of an old battle.

The pathogens will not, of course, give up readily. Our bodies are, after all, their homes and dinners. We understandably tend to see bacteria and viruses as evils, but how anthropocentric this is! Our defenses attempt to prevent the poor streptococcus from getting even a microgram of our body tissues, but if it cannot find a way around our defenses, it will die. So, for each of our defenses, pathogens have evolved counterdefenses. They find ways to get transmitted to us and ways to breach our walls. Once inside, they hide from our sentries, attack our defenses, use our nutrients to make copies of themselves, and find ways to get those copies out of the body and to new victims, often by turning our own defenses to their own advantage. Before describing the clever stratagems used by pathogens to elude our defenses, we will discuss the defenses in more detail.

T
he best defense is avoidance of danger; proper hygiene can prevent a pathogen from gaining that first toehold. Instinctively slapping at a mosquito is not just an attempt to spare oneself the minor annoyance of a mosquito bite. It may also prevent a long list of serious insect-borne diseases, of which malaria is the best known. Is the itch of a mosquito bite just part of the insect’s nastiness? It may be merely an accidental result of the chemicals the mosquito uses to ensure that our blood flows freely, but it may also be our adaptation for avoiding future bites. Imagine what would happen to a person who did not mind being bitten by mosquitoes. And imagine how successful a mosquito could be if its biting were not noticeable!

Our tendencies to avoid contact with people who may be infectious may have the same significance. Likewise, an instinctive disgust motivates us to avoid feces, vomit, and other sources of contagion. Our tendency to defecate away from others may prevent the infection of close associates, and social pressures to conform to such practices may protect us from infection by others. The best defense
against infection is avoidance of pathogens, and natural selection has shaped many mechanisms to help us keep our distance.

O
ur skin is like the wall around an ancient city, a formidable protective barrier. It not only prevents the entry of parasites but also protects against injury by mechanical, thermal, and chemical forces. Unlike induced defenses such as fever, which are aroused only when a particular danger threatens, the skin is constantly present, always on guard. It is tough and much more resistant to puncture and abrasion than the internal tissues it protects. Minor infections here and there are harmless because the skin is constantly being sloughed off the top and renewed from below. An ink stain on the fingers will be gone in a few days, not because the ink has been absorbed or chemically altered but because the stained cells are replaced by others rising from below. Fungal growths or other potential pathogens in surface cells are constantly cast off by this rapid replacement of the epidermis. Sycamores and shagbark hickory trees seem to use the same strategy.

Not only is the skin a good defensive armor in general, it is also good in particular. Those parts of the body that are most in need of armor, such as the soles of the feet, have thicker and tougher skin right from birth. Any particular patch of skin that is subjected to repeated friction, like that at the top edge of a shoe or the tip of a cellist’s finger, grows the thicker skin we call a callus. This adaptive growth, an induced defense, not only minimizes mechanical injury, it also prevents breaks in the skin that could provide entrances for pathogens.

Some of our most useful hygienic behaviors help maintain the skin’s barrier. The most obvious are behaviors that keep nasty things off the skin. Scratching and other grooming maneuvers remove external parasites, important sources of discomfort and disease transmission for most people during most of human history and still problems in less fortunate societies. Benjamin Hart, a veterinarian from the University of California at Davis, has shown just how crucial grooming is to preventing illness in animals. An animal that cannot groom is quickly infested with fleas, ticks, lice and mites, and will
lose weight and fall ill. The mutual grooming of monkeys is not just a ritual, it is preventive health care.

J
ust as an itch can motivate defensive scratching, pain is an adaptation that can lead to escape and avoidance. The skin, sensibly enough, is highly sensitive to pain. If it is being damaged, something is clearly wrong, and all other activities should be dropped until the damage is stopped and repair can begin. Other kinds of pain can also be helpful. While an abstract realization that chewing is impaired because of an abscessed tooth might possibly lead to more chewing with other, unimpaired teeth, the tormenting pain of a toothache far more effectively prevents the pressure on the tooth that would delay healing and spread bacteria. Continued pain from infection or injury is adaptive because continued use of damaged tissue may compromise the effectiveness of other adaptations, such as tissue reconstruction and antibody attacks on bacteria. Pain motivates us to escape quickly when our bodies are being damaged, and the memory of the pain teaches us to avoid the same situation in the future.

The simplest way to determine the function of an organ like the thyroid gland is to take it out and then see how the organism malfunctions. The capacity for pain cannot be removed, but very occasionally someone is born without it. Such a pain-free life might seem fortunate, but it is not. People who cannot feel pain don’t experience discomfort from staying in the same position for long periods, and the resulting lack of fidgeting impairs the blood supply to the joints, which then deteriorate by adolescence. People who cannot feel pain are nearly all dead by age thirty.