The Trouble with Testosterone
Page 19
By the same logic, it is probably a good idea to sleep more during an illness, because sleeping conserves energy. And maybe your joints hurt during a fever to make you conserve energy also—I’m not inclined to run around a lot when I ache all over. But it’s unclear why you should lose your appetite, especially since many features of feeling crummy seem geared toward meeting the need for energy. I’m not particularly convinced by the hypotheses I’ve seen advanced. One, for example, holds that appetite loss helps animal species that are preyed upon by carnivores. Otherwise these animals would be out foraging for food when they are obviously under the weather, inviting predators to attack them. The trouble with this is that card-carrying carnivores also lose their appetite when they’re sick.
The most dramatic feature of feeling crummy, of course, is fever. The energy mobilized during an infection goes to fueling not only the immune system but the shivering muscles as well. During a malarial fever, for example, metabolism increases by nearly 50 percent, and much of this energy expenditure goes toward generating heat. An investment on this scale certainly suggests fever is doing something useful for you. And indeed a number of studies support the idea.
The easiest way to demonstrate the benefits of feverishness would be to infect laboratory animals with something that typically causes a fever and see how they fare when the fever is blocked. You might, for example, administer an antipyretic drug such as aspirin and then monitor what happens to the animals’ immune response, antibody concentrations in the bloodstream, and survivorship. If those measures are worsened, you can conclude that the fever normally helps fight the infection. However, aspirin does a lot of things besides decrease fever (for example, it decreases joint pain), and its antifever effects may not be the cause of any changes you observe. To get around the problem, Matthew Kluger, a physiologist at the University of Michigan Medical School, did one of the most supremely clever studies that I have ever heard of.
Kluger studied lizards—which are, of course, cold-blooded—placing them in a terrarium that was hot at one end and cold at the other, and had a smooth temperature gradient in between. When healthy, the lizards settled down at the point in the gradient where their body temperature would stabilize at 98.6 degrees. But when Kluger infected them with a bacterium, they chose to become feverish—they moved up the gradient to a point where their temperature would rise a few degrees. When Kluger prevented the infected lizards from moving to the hotter end of the terrarium, they were less likely to survive the infection. Running a fever, he concluded, helped.
The reasons for this are at least twofold. First, the immune system works better when you are running a fever. Studies show that T cells multiply more readily and antibody production is stepped up. Second, a fever puts many pathogens at a disadvantage. A wide variety of viruses and bacteria multiply most efficiently at temperatures below 98.6 degrees. But as a fever is induced, their doubling time slows. In some cases the pathogens stop dividing entirely.
Such studies suggest that fever and the host of other changes we suffer are adaptive mechanisms for helping us through the challenge of infection. It’s not a perfect plan; not all bugs, for example, are inhibited by heat, and too high a fever will damage you along with the infectious invader. But as a general strategy it seems to work.
These observations suggest that fever-reducing drugs such as aspirin may not always be such a swell idea. It would be ironic if future research concludes that the best thing to do during an illness is simply to endure feeling crummy. But perhaps you’ll at least draw some comfort in knowing that, as a result of your stoicism, the pathogen is feeling even crummier.
EPILOGUE
Since this piece was published, a trend has emerged that will horrify the scientifically fainthearted. About a decade ago, it was still quite novel to think that immune messengers could also influence brain function, behavior, hormone release, fat metabolism, and other nonimmune aspects of physiology. While this was new and puzzling, it was at least relatively clear-cut, in that IL-1 seemed to account for the fever, CRF release, pain, and sleepiness, while cachectin had dibs on cachexia. Immunologists have been nearly overwhelmed by the discovery of dozens of different cytokines (for example, the interleukins are up to at least the teens in numbers). Naturally, in the last few years, it has turned out that a lot of these cytokines also participate in the regulation of fever, CRF release, pain sensitivity, etc. Some of these cytokines synergize with IL-1 or cachectin, some work independently, and it’s all very confusing. While it is exhausting to try to absorb all these new individual facts, the general picture remains the same—the generic symptoms of feeling crummy don’t just happen to occur offhandedly, but instead arise for adaptive reasons thanks to some very explicit and clever tricks on the part of the immune system.
FURTHER READING
Benjamin Hart’s work on how a wide variety of diseases induces the same generalized crummy symptoms is summarized in B. Hart, “Biological Basis of the Behavior of Sick Animals,” Neuroscience and Biobehavioral Reviews 12 (1988): 123.
For a general introduction for the nonspecialist to the workings of the immune system, see chapter 8 in R. Sapolsky, Why Zebras Don’t Get Ulcers: A Guide to Stress, Stress-Related Diseases, and Coping. (New York: W. H. Freeman, 1994). Chapter 2 also gives a general overview of the workings of CRF and glucocorticoids. For a more detailed overview of the former, see A. Dunn, “Physiological and Behavioral Responses to Corticotropin-Releasing Factor Administration: Is CRF a Mediator of Anxiety or Stress Response?” Brain Research Reviews 15 (1990): 71.
The finding that IL-1 releases CRF from the brain was first reported in R. Sapolsky, C. Rivier, G. Yamamoto, P. Plotsky, and W. Vale, “Interleukin-1 Stimulates the Secretion of Hypothalamic Corticotropin-Releasing Factor,” Science 238 (1987): 522; and F. Berkenbosch, J. van Oeers, A. del Rey, F. Tilders, and H. Besedovsky, “Corticotropin-Releasing Factor-Producing Neurons in the Rat Activated by Interleukin-1,” Science 238 (1987): 524.
The clever fever study is described in M. Kluger, “The Evolution and Adaptive Value of Fever,” American Scientist 66 (1978): 38.
The roles of IL-1 and related cytokines as pyrogens, somnogens, and sensitizers to pain are reviewed in a number of technical papers: R. Bellomo, “The Cytokine Network in the Critically Ill,” Anaesthesia and Intensive Care 20 (1992): 288; F. Obal, J. Fang, L. Payne, and J. Krueger, “Growth-Hormone-Releasing Hormone Mediates the Sleep-Promoting Activity of Interleukin-1 in Rats,” Neuroendocrinology 61 (1995): 559; J. Krueger and J. Majde, “Microbial Products and Cytokines in Sleep and Fever Regulation,” Critical Reviews in Immunology 14 (1994): 355.
The ability of cachectin (also known as tumor necrosis factor) to induce cachexia is reviewed by the discoverers of the phenomenon: B. Beutler and A. Cerami, “Cachectin and Tumour Necrosis Factor as Two Sides of the Same Biological Coin,” Nature 320 (1986): 584. See also: A. Cerami, “Inflammatory Cytokines,” Clinical Immunology and Immunopathology 62 (1992): S3. This is a case of a pattern that frequently pops up in this business. For years, scientists interested in how the immune system can kill some types of tumors studied a compound critical to that, called tumor necrosis factor. Meanwhile, in the next county, other scientists, interested in how the immune system could regulate metabolism and fat storage, were busy with cachectin. Eventually, both groups were able to determine the structures of their compounds and, surprise . . . tumor necrosis factor and cachectin turned out to be one and the same. (This, predictably, led to some tense negotiations as to which name the compound should be called. In a Solomonic solution, it is now called by both names, thereby avoiding needless bloodshed among immunologists.) More and more, immune and endocrine messengers turn out to be versatile, having multiple functions.
Circling the Blanket for God
Hannah Höch, Denkmal II: Eitelkeit (Monument II: Vanity), 1926; copyright 1996 Artists Rights Society (ARS) NY/VG Bild-Kunst, Bonn
A warning: If you’ve gotten this far in this collection, I can now
number you as one of the few faithful readers of this stuff who is not either a close relative or a student trying to get a good grade in my class. Thus, you’ll have to trust me on this and promise to do a few things. First off, if you think you would be offended by an analysis of religious belief in a medical or psychological context, don’t read this. I’m not kidding. However, if you do start reading this and get offended, please, please read this through to the end and see if it still seems as disturbing, or at least disturbing in a different way than you had originally thought.
I. Hearing Voices at the Right Time
History has not been kind to Paul Radin, and I begin by trying to rectify this a bit. The accomplishments of this obscure anthropologist, trained in the school of Franz Boas at the beginning of this century, are at least twofold. First, by dint of having been born to a rabbinic family in Lodz, Poland, and by then devoting his professional career to the anthrolinguistics of Native American tribes of the plains, Radin was probably the only human to have ever walked this planet who could have produced a reliable Yiddish-Sioux phrase book. He never did so. In fact, there is no evidence that he even so much as gave a moment’s thought to the proper Sioux translation of schlemiel or mensch, on the one hand, or the most appropriate Yiddish equivalent of tepee. Nonetheless, the mere fact that he could should entitle Radin to membership in the tentatively emerging pantheon of multiculturalism.
Radin’s second accomplishment was a bit weightier. In 1936, he wrote a book containing an idea that, if taken to its logical conclusion, should undo some of the most cherished underpinnings of Judeo-Christian thought.
Radin’s speculations indirectly cast light on the question of why schizophrenia exists. This is not necessarily an obvious question to ask. Schizophrenia is one of the most catastrophic ways in which the mind can go awry. It is worth reviewing the features of the disease in order to appreciate Radin’s insight and its potential consequences. This is also useful to help counteract an odd misuse of the word “schizophrenia” by the media and by nonexperts. The erroneous view is of schizophrenia as a disease of sudden, unpredictable lurches between emotional extremes—“God, what a schizophrenic day I’m having. First my car wouldn’t start this morning and I got to work really late. But then I landed this account I’ve been angling for, for months. Then, at lunch I had this really upsetting argument with a friend. What a schizy day.”
In contrast to this incorrect picture, schizophrenia is a disease of disordered thought. The marvel of it is that the cognitive tumult is not just random, but has surprisingly consistent patterns from one sufferer to the next.
Above all else, schizophrenics show “loose associations.” Most of us might relate an incident in a way where there is an obvious logical progression from one step to the next. Schizophrenics, in contrast, produce a storm of non sequiturs or make leaps that, while having a certain strained connectiveness, are not the ones anyone else would make: “So I guess I’ve been a real disappointment to my parents. After all they did for me to get a good education, you know what I’ve wound up doing? I’m a caddie. A caddie. And no one wants caddies these days. Everyone wants the Japanese cars.”
Schizophrenics also have problems with levels of abstraction. Most of us can hear a story and intuit readily whether it is meant to be a factual, literal relating of events, or a parable, meant to be taken symbolically. We intuit whether the point of a particular story is the trees or the forest. Schizophrenics lack that intuition, and their bias is to perceive things on the far more literal, detailed level. “Concreteness” is the term for it and it manifests itself endlessly:
THERAPIST: Hello, Mr. Smith, what’s on your mind today?
PATIENT: My skull.
Or:
THERAPIST: Tell me, what do apples, bananas, and oranges have in common?
PATIENT: They all are multisyllabic words.
THERAPIST: Anything else?
PATIENT: They all contain letters that form closed loops.
For schizophrenics, it’s not a matter of trees and forests. Instead, it’s habitually seeing only the bark.
Schizophrenics are also prone toward delusions, inserting themselves into situations, making claims that cannot be so, and seemingly believing them. (“Heard of the Great Wall of China? Yes? My idea. The emperor came to me at night with a map and I said, ‘Here’s where it goes.’ ”) Related to this are the hallucinations, predominantly auditory, that are defining features of the disease. And related to this is the tendency in many schizophrenics toward a florid, permeating paranoia. (“What do apples, bananas, and oranges have in common?” “They’re all wired for sound.”)
Add to that some of the other features of the disease less related to thought—an inappropriate flattening of emotions, an aching social isolation, a tendency toward horrifying acts of self-mutilation and suicidalism—and you have one of the great medical tragedies to befall a person.
One might ask why should schizophrenia exist in culture after culture on this planet, as it does. The disorder has a genetic component (and by this I mean the modern view of human behavioral genetics—not that there is a gene that inevitably causes schizophrenia, but that there are genes that make the individual more sensitive to schizophrenogenic triggers in the environment). The disorder runs in families. Studies of adopted individuals showed that the trait is more common among the genetic, biological pedigree, rather than through the nongenetic, adoptive one. And currently, molecular biologists search for the actual genes, the precise DNA sequences, relevant to the disease.
Thus, if there is a genetic component to the disease, no matter how small, when one asks, Why should schizophrenia exist? one is actually asking, Why should the gene(s) involved in schizophrenia have evolved and been maintained by natural selection in the human gene pool?
Evolution, we were all taught in ninth-grade biology, is the process by which genetic traits are passed on over time and become more common only if they are advantageous. Once, long ago, when giraffes had the short necks of most mammals, one had a somewhat longer neck for a genetically based reason. And that giraffe could reach leaves higher up in the tree, was fruitful, and multiplied . . . and now it is that giraffe’s long-necked descendants who stroll around the savannah. Evolution, we were taught, works something along those lines. So what’s the evolutionary advantage to schizophrenic genes? Schizophrenics are “unfit” in strict evolutionary terms, which is to say that they have a lower reproductive rate, and thus pass on fewer copies of their genes, than do healthy individuals. Then why is this disorder being maintained in the population?
The answer probably lies in a facet of genetics that we all also learned in ninth grade. Sometimes, genetic traits can come in different degrees of severity, and while the full-blown version of such a trait may be disadvantageous, the moderately “penetrant” version that occurs in a relative may carry a big advantage. And if the magnitude and frequency of the advantageous form outweighs the deleterious, the trait will be selected for in the population. The classic example is sickle-cell anemia affecting people of African descent. In its extreme form, it is a lethal hematologic disorder, while in its less penetrant form, it protects against malaria. There is evidence for a similar pattern in Tay-Sachs disease among Ashkenazi Jews. In its full-blown form, it is a fatal neurological disaster. In its milder form, some data suggest, it confers protection against tuberculosis. There’s also the suggestion that the gene for cystic fibrosis protects against cholera.
Schizophrenia probably shows this pattern. What would be the mild, advantageous version of schizophrenia? As was mentioned in the first piece in this volume, this form is now called “schizotypal” personality disorder. Schizotypals are not the dysfunctional isolates that schizophrenics are. They just tend toward solitary hobbies and professions, are uncomfortable in social situations involving unfamiliar people, are aloof, with few close friends. They are the fire tower rangers, the lighthouse keepers, the film projectionists alone each night in their booths. Moreover, schizotypa
ls are not floridly delusional, hallucinating like schizophrenics. Their disordered thoughts and behaviors are far subtler, in that they have a tendency toward what is termed the “metamagical.” They may have an extremely strong interest in science fiction and fantasy, or in some New Age paranormal belief such as ESP or levitation. They often report odd perceptual experiences—sensing spirits in a room, seeing illusions. Or, as a foreshadowing of the tumult to come, they may have a profound faith in very literal, very concrete interpretations of religious dogma—it really is possible for Jesus to have walked on water, the Patriarchs truly lived for nine hundred years, the creation of the world in seven days is reporting of precise fact rather than a parable. Schizotypal personality disorder was first recognized in precisely the population where you would expect it—among close relatives of schizophrenics, among those individuals who share a certain percentage of genes with schizophrenics.
It is important to recognize that none of these traits count as all-out mentally ill in the conventional sense used by most in society, in which “crazy” is most usually akin to the shattering psychosis of schizophrenia. Perfectly respectable businessmen may sneak off to their Star Trek conventions, an erstwhile actress may publish a best-selling account of her previous lives, a First Lady may consult astrologers and still be taken seriously in the fashion pages.
Who are the schizotypals? Not the lone schizotypal operating the film projector in a movie theater, sensing the presence of Elvis in the room. I mean who were the schizotypals in preindustrial societies, throughout 99 percent of our human history? Here is the key. In 1936, Radin was the first to advance the idea that many shamans, witch doctors, and medicine men (and women) are “half-crazy.”