Why We Get Sick (7 page)

Generalized aches and pains, or merely feeling out of sorts (malaise, in medical terminology), are also adaptive. They encourage a general inactivity, not just disuse of damaged parts. That this is adaptive is widely recognized in the belief that it is wise to stay in bed when you are sick. Inactivity also likely favors the effectiveness of immunological defenses, repair of damaged tissues, and other host adaptations. Medication that merely makes a sick person feel less sick will interfere with these benefits. This is fine when patients are
well informed about the risks and realize that they are sicker than they feel and should make a special effort to take it easy. Otherwise, a drug-induced feeling of well-being may lead to activity levels that interfere with defensive adaptations or repairs.

T
he body must have openings for breathing, for the intake of nutrients and expulsion of wastes, and for reproduction. Each of these openings offers pathogens an invasion route, and each is endowed with special defense mechanisms. The constant washing of the mouth with saliva kills some pathogens and dislodges others so they can be destroyed by the acid and enzymes in the stomach. The eyes are washed by tears laden with defensive chemicals and the respiratory system by antibody and enzyme-rich secretions that are steadily propelled up to the throat, where they can be swallowed so the invaders can be killed and the protein in the mucus recycled. The ears secrete an antibacterial wax. Projections inside the nose, called turbinates, provide a large surface that warms, moistens, and filters pathogens from the incoming air. Mouth-breathers don’t get the full benefit of this defense and are more subject to infection. The nose and ears have hairs strategically arrayed to keep out insects.

The defenses at each body opening can be quickly increased if danger threatens. Irritation of the nose by a viral infection provokes the discharge of such copious mucus that one can go through a whole box of tissues in a day. Millions of people use nasal sprays each year to block this useful response, but there are remarkably few studies that have investigated whether the use of such devices delays recovery from a cold. If they do not demonstrably delay recovery, as seems to be the case from the limited data, it would be evidence that a runny nose is not a defense but an example of a pathogen manipulating the host’s physiology in order to spread itself. Sneezing is obviously a defensive adaptation, but not every sneeze need be adaptive for the sneezer. Some sneezing may possibly be an adaptation that viruses use to disperse themselves.

Irritation deeper in the respiratory tract induces coughing. Coughing is made possible by an elaborate mechanism that involves detecting
foreign matter, processing this information in the brain, stimulating a cough center at the base of the brain, and then coordinating muscle contractions in the chest, the diaphragm, and the tubes in the respiratory tract. All along the lining of these tubes tiny hairs called cilia beat in a steady rhythm, sweeping pathogen-trapping mucus upward. In the urinary tract, periodic flushing washes pathogens away along with the cells on the surface of the urethral lining, which are systematically shed like those on the skin. When the bladder or urethra becomes infected, urination understandably becomes more frequent.

The digestive system has its own special defenses. Bacterial decomposition and fungal growths produce repulsive odors, the repulsiveness being our adaptation to be disinclined to put bad-smelling things into our mouths. If something already in the mouth tastes bad, we spit it out. Taste receptors detect bitter substances that are likely to be poisonous. After we swallow something, there are receptors in the stomach to detect poisons, especially those made by bacteria that multiply in the gastrointestinal tract. When absorbed toxins enter the circulation, they pass by a special group of cells in the brain, the only brain cells directly exposed to the blood. When these cells detect toxins, they stimulate the brain’s chemoreceptor trigger zone to respond first with nausea and then with vomiting. This is why so many drugs are so nauseating, especially the toxic ones used for cancer chemotherapy.

Circulating toxins almost always originate in the stomach, so it is easy to see how vomiting is useful: it ejects the toxin before more is absorbed. What about nausea? The distress of nausea discourages us from eating more of the noxious substance, and its memory discourages future sampling of whatever food seemed to cause it. Just a single experience of nausea and vomiting after eating a novel food will cause rats to avoid it for months; people may avoid it for years. This remarkably strong onetime learning was named the “sauce béarnaise syndrome” by Martin Seligman, a psychologist who recognized its significance after contemplating the untimely loss of his gourmet dinner. Why is the body capable of such a strong association after a single exposure to a food that produces illness? Imagine, for a moment, what would happen to the person who ate poisonous foods repeatedly.

The other end of the intestinal tract has its own defense, diarrhea. People understandably want to stop diarrhea, but if relief comes from merely blocking the defense, there is likely to be some
penalty. Indeed, H. L. DuPont and Richard Hornick, infectious disease experts at the University of Texas, found just this. They infected twenty-five volunteers with
Shigella
, a bacterium that induces severe diarrhea. Those who were treated with drugs to stop the diarrhea stayed feverish and toxic twice as long as those who did not. Five out of six who received the antidiarrheal drug Lomotil continued to have
Shigella
in their stools, compared to two out of six who did not receive the drug. The researchers concluded, “Lomotil may be contraindicated in shigellosis. Diarrhea may represent a defense mechanism.” Consumers will no doubt want to know when they should and should not take such medications for more commonplace diarrhea, but the needed research has not been done. There are dozens of studies of side effects, of safety, and of the effectiveness of medications that block diarrhea, but few consider the consequences of the main effect of blocking a normal defense.

Our reproductive machinery requires yet another opening, which in males is the same as that of the urinary tract, whose defenses thereby do double duty. Women have a separate opening that poses a special problem for defense against infection. While the female reproductive tract uses many defenses, such as cervical mucus and its antibacterial properties, one largely unappreciated defense is the normal outward movement of secretions that makes it difficult for bacteria and viruses to gain access. These secretions move steadily from the abdominal cavity through the fallopian tubes, uterus, cervix, and vagina to the outside. There is one noteworthy exception to this constant downstream movement. Sperm cells swim upstream, from the vagina through the uterus into the fallopian tubes and the pelvic cavity. Unusually small for human cells, sperm are still large compared to bacteria. Potential pathogens can stick to sperm cells and be transported from the outside to deep within a woman’s reproductive system.

Only recently has the threat of sperm-borne pathogens been recognized. Biologist Margie Profet notes that menstruation has substantial costs and argues that
it
must therefore give some compensating benefit. After a consideration of the evidence, she concluded that many aspects of menstruation seem designed as an effective defense against uterine infection. The same anti-infection benefits that come from sloughing off skin cells are achieved by the periodic extrusion of the lining of the uterus. This is supported by evidence that menstrual blood differs from circulating blood in ways
that make it more effective in destroying pathogens while minimizing losses of nutrients. Studies of menstruation in other mammals suggest that each species menstruates to just the extent appropriate for its vulnerability to sperm-borne pathogens. The threat is small for species that restrict their sexual behavior to widely separated fertile periods, but women’s continuous sexual attractiveness and receptivity are largely unrelated to the ovulatory cycle. This extraordinary amount of human sexual activity may have its benefits, as we will discuss in
Chapter 13
, but it substantially increases the risk of infection. This risk may be responsible for the unusually profuse human menstrual discharge, as compared to other mammals’.

We have mentioned several times that evolutionary hypotheses need to be and can be tested. Beverly Strassmann has mounted a challenge to the hypothesis that menstruation protects against infection. She maintains that the pathogen load in the reproductive tract is the same before and after menstruation, that menstruation does not increase when there is infection, and that there is no consistent relationship between the amount of sperm females in a particular species are exposed to and the amount of menstrual flow. As an alternative explanation, Strassmann proposes that the degree of shedding or reabsorption of the uterine lining depends on the metabolic costs of maintaining it or shedding it, a hypothesis that she supports with comparisons between species and the relationship between menstruation and the body weight of the female and her neonate. Obviously, we have not heard the last word on this issue.

V
ertebrates in general, and mammals in particular, have amazingly effective immunological defenses that are in essence a system of carefully targeted chemical warfare. Cells called macrophages constantly wander the body searching for any foreign protein, whether from a bacterium, a bit of dirt in the skin, or a cancer cell. When they find such an intruder, the macrophages transfer it to a helper T cell, which then finds and stimulates whichever white blood cells can make a protein (called an
antibody
) that binds specifically to that particular foreign protein (an
antigen
). Antibodies bind to antigens on the surfaces of bacteria,
thereby impairing the bacteria and also labeling them for attack by specialized larger cells. If the antigens persist, say during a continuing bacterial infection, they stimulate the production of ever more of the cells that make that specific antibody, so that the bacteria are destroyed at an ever-increasing rate. Whatever is recognized as a properly functioning part of the body is permitted to remain. All else—disease organisms, cancerous tissue, organs transplanted from other individuals—is attacked.

How does the body recognize cells as its own? Each cell has a molecular pattern on its surface, called the
major histocompatibility complex
(MHC), which is like a photo ID card. Cells that have a valid MHC are left alone, but those that have a foreign or missing MHC are attacked. Interestingly, when cells are infected, they transport protein from the invader to the MHC, where it is bound. Like individuals with obviously fake ID cards, such cells are priority targets for the killer cells of the immune system. The adenovirus, a common cause of sore throats, has found a way to get around this defense. It makes a protein that blocks the ability of the cell to move foreign proteins to the MHC. In essence, it prevents the infected cell from signaling that it has been invaded.

The operation of the MHC system is a vivid example of altruism in its biological sense. An infected cell “volunteers” for destruction for the good of the rest of the body. This is like a soldier with plague asking his comrades to destroy him before he infects them. The analogy, however, is false in one crucial respect. The cell’s comrades are genetically identical, and its only chance for passing on its genes lies in the success of the whole organism. Soldiers, however, seldom share foxholes with identical twins and are understandably less likely to volunteer for elimination.

The weapons of the immune system are truly fearsome. They include general inflammation, several kinds of antibodies—each specialized for a different group of opponents—and a series of chemicals (the complement system), five of which attack the targeted cells, boring holes in their membranes and digesting them. Despite these weapons, some invaders can nonetheless persist. When a clump of bacteria can be neither expelled nor destroyed, it may be walled off by a membrane that keeps it away from vulnerable tissues. The tubercles from which tuberculosis gets its name are the best-known example, but analogous imprisonment of roundworms and other multicellular parasites has also been important throughout most of human evolution.

I
n the contest with their host, pathogens must rob the host to secure their own nourishment. Various bacteria and the protozoa that causes amoebic dysentery secrete enzymes that digest nearby host tissues and then absorb the products of digestion. Others literally eat through host tissues, for example, filaria worms, which live in the anterior part of the eye, or the larvae of another species of worm,
Angiostrongylus cantonensis
, which burrow through the brain. Both of these defend themselves with secretions that inhibit inflammation. Still others, such as the trypanosomes, a group of protozoans that cause diseases such as African sleeping sickness, live in the bloodstream and absorb nutrients directly from the plasma. Whatever the means, parasites secure their resources from the host and then use them for their own maintenance, growth, and reproduction.

These activities of pathogens incidentally damage the host, but this damage is not a pathogen adaptation. It does not do a tapeworm any good to have its host malnourished. It does not do the malarial parasite any good to destroy its host’s blood cells (unless, perhaps, this frees up iron for use by the parasite). Most often, the opposite must be true. The survival and well-being of the parasite depend on the host’s continued survival and ability to provide it with nourishment and shelter. Such incidental damage must therefore be considered a cost to both host and pathogen.

The cost may be a general reduction in host resources or an obviously localized destruction. Bacteria that attack bone where a tooth is rooted cause structural damage and perhaps the loss of the tooth. The bacteria that cause gonorrhea may erode the connective tissue and cartilage of joints, causing functional impairment. Hepatitis viruses may destroy substantial portions of the liver, so that all liver functions, such as the clearing of toxins from the blood, become less effective. Such functional impairments are simply incidental consequences of pathogen adaptations. It does not do bacteria any good to make the host’s chewing less effective or its running less rapid.