Excerpt
from Riddled with Life: Friendly Worms, Ladybug Sex, and the Parasites that Make Us Who We Are
by Marlene Zuk
Grasshoppers, Aspirin, and The Best Defense
Pain and suffering are hallmarks of disease, and while philosophers and poets can wax eloquent about their benefits to the spirit, both physicians and their patients are united in wanting to eliminate them from the body. All forms of suffering are not created equal, however, and Darwinian medicine helps us understand the consequences of assuming that they are. Pain itself is a useful signal, of course. The few individuals born without the ability to feel pain lead very complicated and controlled lives and generally die at an early age. It is easy to understand why; we rely on pain to tell us when to move our hand from a hot stove or how far to bend a joint. But what about disease symptoms that range from annoying, like the itch of a mosquito bite, to debilitating, like the cough of pneumonia? What about the general malaise, the mopiness and lethargy that accompany a wide range of illnesses? Could they, too, serve a useful purpose?
In particular, what about fever, the ubiquitous partner of illnesses ranging from colds to malaria? Fever is the most common reason for parents to bring their children to the hospital emergency room, and millions upon millions of dollars are spent each year on fever-reducing drugs like acetaminophen, ibuprofen, and aspirin. Most parents believe that high fevers, those above 104° F (40° C), are dangerous, and can cause brain damage if left untreated.
But Hippocrates was a strong advocate for the beneficial effects of fever, believing that it burned off excesses of the humors or essences of the body, and many cultures around the world used to induce fever to treat disease; in at least one Native American tribe, a sufferer was placed inside the carcass of a freshly slaughtered horse to absorb the heat lingering in the body cavity. In 1927, the Nobel Prize for medicine went to Julius Wagner-Jauregg, an Austrian physician who had tried many cures for the fatal paralysis caused by late-stage syphilis. His breakthrough came when he deliberately infected syphilitic patients with malaria to induce high fevers; most of them showed striking disease remission, whereupon he cured the malaria with quinine. Wagner-Jauregg was not completely certain why his treatment worked, pointing out in his Nobel acceptance speech that the high temperature alone was not the sole mechanism behind recovery. He speculated that the fever activated some other component of the body's natural disease resistance, but had little information to support this suggestion, since the workings of the immune system were only beginning to be understood. More recently, malaria therapy has been suggested for the treatment of Lyme disease, some forms of cancer, and even AIDS, but it is viewed with considerable skepticism by the medical establishment.
Worse Than The Disease?
So what about that widespread use of drugs to lower fever in children? Practices are changing, albeit slowly. Some medical practitioners now warn against "fever phobia," the needless panic felt by many parents and health care providers when a child's temperature rises. A paper published in the Bulletin of the World Health Organization surveyed numerous studies on the use of fever-reducing drugs in children and came to the rather startling conclusion that they made no difference in the outcome of the disease, the duration of the symptoms, or even the comfort level of the children themselves. In one of the studies, parents were not told whether they were giving their children a potent drug or an inactive placebo (they agreed to this in advance). When asked which they thought the child had received after the sickness was over, the parents guessed right about half the time, exactly what you would expect by chance. A slightly higher degree of activity and alertness was noted in the children receiving the medication, but this was minor. The authors acknowledge that this is not the final word on the subject, but it does give food for thought.
Medical researchers have also debunked two commonly held misconceptions about high fever in children: that it can result in dangerous seizures, and that fevers from infection must be controlled before they reach a certain point, often 41°C (I06°F), to prevent seizures and brain damage. Febrile seizures, as they are called, are certainly frightening to watch, but they tend to occur early in the fever process, rather than after fevers have mounted, and a small percentage of children simply seem to be prone to them; administering fever-reducing medicine does not stave off their recurrence. They also do not have permanent ill effects, and although parents are advised to notify the doctor if their child has one, they are not necessarily a cause for alarm. And while it is true that fevers over I06°F are potentially damaging, such high temperatures are virtually always the result of heatstroke or brain injury, not infection, and so fears of a cold -- or flu -- caused fever rising to this level are groundless. Michael S. Kramer and Harry Campbell, two child-health experts writing in a document for the World Health Organization, say, "One is left to conclude that the principal rationale for antipyretic [fever-reducing] therapy is to soothe worried parents and health care workers and to give them the sense that they are controlling the child's illness, rather than it controlling them."
This is ironic, since it is not so simple as us versus them. Fever, as a mechanism that activates the immune system to cure us of the pathogen, is a defense, a tool on our side, and the best way to control an illness is to leave the fever alone, at least some and perhaps most of the time. Certainly we can choose to suppress fever if we have a task to do that requires a more alert mind, but we need to be mindful of the price that exacts.
And it's not just fever. Other symptoms that bear reevaluating include coughs, which can rid the lungs of harmful matter; diarrhea, which likewise sends the offending agent rapidly through the digestive system; and even the behavioral accompaniments of illness such as sleepiness and lethargy. Many animals exhibit sickness behaviors like those of humans; they go off by themselves, refuse to eat, and do the zoological equivalent of watching daytime television. Some veterinarians and researchers suggest that these behaviors are more than the side effects of infection; they could be defenses that help speed recovery by allowing energy to be directed at healing. "Soldiering on" during a bout of flu may thus do more harm than good.
Reduced appetite during sickness is a particularly interesting symptom, because it may be linked to a mechanism for eliminating virus-infected cells from the body. Such illness-associated anorexia, as distinct from the eating disorder anorexia nervosa, is a hallmark of many diseases, including AIDS. Many doctors attempt to treat it and get the patient eating again, but Edmund LeGrand, a researcher with Johnson & Johnson, wondered whether the controlled starvation during illness might serve a function. In particular, he suggested that it might favor a kind of directed cell suicide called apoptosis. Apoptosis is a complex and orchestrated process, distinct from simple cell disintegration in the way that fever differs from heatstroke, and it targets cells that are already infected with virus particles, which can help control the disease. Food restriction makes this process happen more easily, and LeGrand speculates that the wasting seen during HIV infection might actually be beneficial. This is not to say that extreme weight loss and lack of nutrients during disease is helpful and should never be treated, but it is possible that the mild loss of appetite associated with some illness is therapeutic.
While leaving some diseases to run their course may be best, we are obviously not going to stop all forms of treatment, nor should we. Some manifestations of disease are defenses, but others are defects. Again, however, thinking about medications in light of our relationship with disease is useful. Our bodies' regulatory systems, which maintain everything from our internal salt and water balance to our flow of oxygen, tend to respond to any perturbations by attempting to get those mechanisms back to the way they were before. Drugs that mediate one of these regulatory systems, maybe by altering the production of a hormone, spark the regulatory system to fight back, so to speak, which makes the drug less effective.
Take, for example, the use of leptin to treat obesity. Leptin is a substance produced by fat cells; it helps regulate a variety of systems including appetite. The more body fat a person has, the more leptin he or she produces, and at least in laboratory rodents, that reduces appetite and promotes weight loss. But administering leptin to obese people doesn't help much, and in fact it turns out that such people actually have higher levels of circulating leptin than those who are not overweight. What's going on? The answer may lie in the evolution of the regulatory system. It is reasonable to suppose that humans evolved stronger mechanisms for gaining weight and keeping it on than for taking it off, since the risk of starvation was far more real than the risk of eating too many Oreos. Scientists suspect that under normal, or at least pre-Oreo, conditions, hunger levels went down when leptin levels increased. If we were starving, however, appetite was stimulated by low leptin levels and the brain was told to increase fat storage and maintain vital body processes, maybe even at the expense of reproduction. The problem is that weight loss in an overweight person can look like starvation to his brain, so his regulatory system compensates for the leptin drop by increasing appetite and encouraging weight gain. The system has no way of knowing that the new weight is healthier than the old one -- recognizing obesity simply wasn't necessary in most of our evolutionary past. Any treatment of obesity needs to take this evolutionary heritage into account. Researchers are toying with altering the baseline levels of leptin, so that the system is short-circuited at an early stage, before the delusion that starvation is occurring sets in.
Randy Nesse advocates using the smoke-detector principle in deciding whether to treat a defense symptom. Smoke detectors are designed to be sensitive to any amount of smoke, even if that means having to listen to the earsplitting screech after burning toast, because the cost of such a false positive is much lower than the cost of the false negative of ignoring a smoldering cigarette in the bed. Similarly, the body's defenses err on the side of safety. Some defenses are all-or-none, like vomiting; we can't stop halfway, as it were. Others are graded, like fever, where the rise in temperature can be slight or marked. The all-or-none defenses should occur when the cost of responding is relatively low compared to the cost of doing nothing; expelling a poisonous food costs only the calories consumed and the energy in eliminating them, while leaving the toxin in the body might be very costly indeed. More graded responses should be more conservative, because it is easier to fine-tune exactly how high a temperature increases. This means that we have some leeway, particularly for the high end of the graded responses. In other words, going ahead and treating fever may not hurt, since the defense mechanism is oversensitive and fever may kick in at a level of illness where it is not essential to raise the body temperature. In general, though, if a symptom is caused by the host, rather than by the pathogen, we are best off leaving it alone.
Copyright © 2007 by Marlene Zuk