The Trouble with Testosterone

by Robert M. Sapolsky

  I have occasionally been able to observe that flicker. As a benefit of my years spent working intermittently in East Africa, I have often accompanied African friends to their homes, some hamlet clinging to a mountainside. Invariably, it would be obvious that my friend had become almost as much of an outsider as I was. By definition, if I knew this person, he was the one who had left. The second son, the restless one, the one who had gotten some schooling, a far-off job among other tribespeople, the one stumbling over words in his mother tongue, returning with new ways and a white friend.

  And it would always be the same sort of world that my friend had left. There would be one old man who was The Old Man, one damaged village idiot who wandered the slopes, one drunkard wife-beater. And at the friend’s house, there would always be the older brother, the first son, the one who had stayed. He would sit next to his aging father—silent, inexpressive farmers, unsophisticated men who spoke no English or Swahili, who had been to the county seat once, but no farther. They would sit there, half amused and half puzzled by some hyperverbal story told about the big city by my friend, grunting in unison in the same phlegmatic way. It is a world without our Western frenzy for individuation. In the schools, Peace Corps teachers would find it maddening that kids won’t give answers when they know them; for fear of shaming their peers, kids are embarrassed to stand out. “The tall sheath of wheat gets cut first,” goes the saying. It is a world where no parent thinks, “I want better for my kids,” where it is absurd to ask a child what he or she wants to grow up to be. No one would ever wonder if it’s a bit unhealthy for a thirty-year-old to still be living near the parents, or view joining the family business as a worrisome lack of independence. In this tough world, you’re lucky if you wind up farming the same land or raising your kids the same way as your parents did, if you, as with these older brothers, turn into your parent, your identities melding.

  Thomas Mann, in his retelling of the Bible story in Joseph and His Brothers, captures this. He describes young Joseph hearing the stories of old Eliezer, his father’s servant, stories told in the first person that were the experiences of the Eliezer, the servant of Abraham from the mythic past. Mann describes how it was perceived as normal “that the old man’s ego was not quite clearly demarcated, that it opened at the back, as it were, and overflowed into spheres external to his own individuality both in space and in time; embodying in his own experience events which, remembered and related in the clear light of day, ought actually to have been put into the third person.” This Eliezer was not sharing parts of his life with the mythic one. Instead, as he aged, he had become the mythic Eliezer, and the community had expected him to do so.

  It is the triumph of archetypes. In every traditional community, there is an Eliezer, the freedman who has become the wise servant. There must be an Esau, the primal force of simplicity, there must be the fratricidal conflict of brothers over the blessing of the ailing father, there must be an Abraham, the Ur-Patriarch. These needs transcend individual rights to a bounded ego, and people would be named and raised to be the next incarnation. An Abraham would always live nine hundred years, because in each community there would be that Abraham—he would simply need to inhabit a new body now and then.

  This is not Jaynes’s view, where there is not yet a sense of self. That sense is simply not that important, subordinated to something bigger and tribal.

  This primacy of continuity is something we no longer have, and to feel even its glimmer, as I did, requires an emotional crisis, perhaps coupled with some seasoning. My students usually come with ego boundaries like exoskeletons. Most have no use for religion, precedents, tradition, or ritual, or if they do want ritual, it is not vertical over time, but newly minted and shared horizontally within their age-group. The ones who I train to become scientists go at it like the warriors they should be, overturning existing knowledge and reigning paradigms, each discovery a murder of their scientific ancestors. And if I have trained them well, I must derive whatever satisfaction I can from the inevitability of becoming their Oedipal target someday. In many ways, competitive science represents the most jagged version of our Western model, in which torches are wrested, rather than passed, intergenerationally. These students are right on maturational schedule in believing that they have burst anew free of sources and that they can reinvent the world within themselves. And if they should happen to find themselves becoming confused as to where they end and somebody else begins, it is obvious that they are dealing with something scientifically, certifiably abnormal.

  That is becoming less the case for me. I can still do without religion, but some ritual would be nice. There’re other changes. I watch these damn kids sprint past me when I play soccer; I fumble for an answer when watching Jeopardy! that the high school contestants jump on. My beard is showing some white; my spine has probably started shrinking while my refractory periods have lengthened. Another few birthdays and it becomes prudent to have a physician regularly poke around my prostate. It slowly dawns that my ego-bounded self is not such a hot deal anymore.

  A tribal mind-set cannot be reattained; we cannot turn back. It can only come as an echo, a hint in our armored individuated world that a bit of confusion as to ego boundaries can be an act of health, of homage and love, and can be a whisper of what it feels like to be swaddled in continuity. It is a lesson, amid our ever-expanding array of scientific labels, on the risks of overpathologizing. Most of all, it is a lesson that it would not be so bad, in fact it would even be a point of pride, if in the end, someone mistakes you for him.

  For my father, Thomas Sapolsky, 1911-1994.

  FURTHER READING

  For an overview of the split-brain literature, see two books by Sperry’s principal student and collaborator in the work: M. Gazzaniga, The Bisected Brain (New York: Appleton-Century-Crofts, 1970); and M. Gazzaniga, The Cognitive Neurosciences (Cambridge, Mass.: MIT Press, 1995). For a summary of Sperry’s view of the work, see R. Sperry, “Consciousness, Personal Identity and the Divided Brain,” Neuropsychologia 22 (1984): 661. And for discussion of laterality of function in the brain, see N. Geschwind, “Cerebral Dominance in Biological Perspective,” Neuropsychologia 22 (1984): 675.

  For Jaynes’s controversial ideas, see his 1977 book: J. Jaynes, The Origin of Consciousness in the Breakdown of the Bicameral Mind (Boston: Houghton Mifflin, 1977).

  For a discussion of multiple personality and other “dissociative” disorders, see D. Spiegel, Dissociation. (Washington, D.C.: American Psychiatric Press, 1994). Dr. Spiegel was the psychiatrist paraphrased who contributed heavily to the new formulation concerning multiple personality disorder. This can be found in Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (Washington, D.C.: American Psychiatric Association, 1994).

  For Freud, see “Mourning and Melancholia,” in The Collected Papers, vol. 4 (New York: Basic Books, 1959).

  The Mann quote comes from Joseph and His Brothers (New York: Knopf, 1934).

  Why You Feel Crummy When You’re Sick

  Robert Longo, Pressure, 1982–83; courtesy Metro Pictures, New York

  Recently, in preparation for a trip to the tropics, I received a dreadful number of inoculations. As I sat in the clinic after the shots, shifting from cheek to cheek in discomfort, the nurse explained that the vaccines—especially the one for typhoid—could make me feel a bit ill. And, sure enough, by nightfall I felt crummy.

  It was a particularly unpleasant bout, because somehow it felt illegitimate. I wasn’t really ill. I didn’t have to worry that I had malaria or the flu or the plague. I knew what the cause was, and it wasn’t serious. Vaccines, in essence, work because they fool the body into thinking it’s just a little bit sick and had better defend itself. We’re generally unaware of the mock battle being staged, but some vaccines, including typhoid shots, produce an unusually strong effect. So I couldn’t really feel sorry for myself, and besides, I knew I’d be fine in the morning. In an odd way it was all form and no content—I felt sick without actual
ly being sick.

  An extraordinary array of illnesses make us feel crummy in this way. We want to sleep at all hours of the day. Our joints ache, and we feel cold and feverish. Sex loses its appeal. We lose interest in food; if the illness persists, we lose weight even if we force ourselves to eat. And we look like hell. Not long ago Benjamin Hart, a veterinarian at the University of California at Davis, listed sixty-odd common diseases in mammals that produce the same array of symptoms, despite their infecting different organs. Give a person influenza, which affects the respiratory system, give a cat infectious anemia, which affects its blood, give a sheep enterotoxemia, which affects its gut, and all will get achy and mopey and feel like putting on flannel pajamas.

  Traditionally, such symptoms were not considered terribly interesting from a medical standpoint. Suppose you had the flu and complained to your doctor that you felt weak and your joints ached. I’d wager that the most common answer would be “Of course you feel weak. Of course your joints ache. You’re sick.” The symptoms are so nonspecific and ubiquitous that they seem almost not to count. But in recent years researchers have discovered a great deal about why we feel crummy when we have infectious diseases. These symptoms don’t just happen; instead, your body works to bring them about—and, it seems, for very sound reasons.

  At the center of this story is the immune system and the various white blood cells it employs to fight off disease. When a pathogen—an infectious bug such as a virus or bacterium—invades the body, it is the immune system that first sounds the alarm: the invader is promptly grabbed by a large scavenger cell called a macrophage. The macrophage in turn presents the bug to a helper T. cell, which signals that the noxious foreigner is indeed worth getting excited about. The macrophage then sets off a chain of events culminating in the activation of killer T cells that attack the intruder. This cascade is referred to as cell-mediated immunity.

  Meanwhile, a second form of defense, known as humoral immunity, is also set in motion: the helper T cells stimulate yet another type of white blood cell—B cells—to divide, differentiate, and ultimately produce antibodies to the intruder. These in turn will grab hold of the infectious organism and immobilize it.

  Sorting out this process has kept immunologists off the streets for decades. What they’ve learned is that the immune response involves a variety of cell types scattered throughout the body. To communicate with far-flung members, the immune system uses cytokines, chemical messengers that travel in the bloodstream and lymph fluid. And that’s where feeling crummy begins to come into the picture.

  Among the best known of these messengers are the interferons, which activate a type of white blood cell that fights viruses and cancer, and the interleukins, which are central to the T. cell cascade. The interleukin of greatest interest to us here is called IL-1 (for interleukin-1); its principal job is to carry the alarm message from the macrophage (where it is made) to the T cells. But we begin to feel crummy because that is not all that IL-1 can do; it can also influence the brain.

  Most dramatically, this interleukin alters temperature regulation. For years it was known that, after infection, the immune system produced something that caused fever. No one knew what it was, and the putative messenger was called endogenous pyrogen, a term whose derivation should be familiar to pyromaniacs and Pyrex manufacturers among the readership. Not until the early 1980s was IL-1 identified as the pyrogen.

  A part of our brain called the hypothalamus functions much like a thermostat. Normally it is set for 98.6 degrees. If body temperature drops below that, you shiver to generate heat, divert blood from the periphery of your body to vital organs, and pile on the blankets. Temperatures above 98.6 cause you to sweat and breathe faster to dissipate heat. What IL-1 does is cause the set point to shift upward. In other words, you begin to feel cold at 98.6, the various warming responses kick in, and a new equilibrium is reached at a higher temperature. You are now running a fever.

  But that’s not the only way IL-1 makes us feel crummy. A few years ago two research groups (my own and a group in Europe) simultaneously reported that the chemical also causes the hypothalamus to release a substance called corticotropin-releasing factor, or CRF. This substance runs the body’s hormonal response to stress by initiating a cascade of signals going from the hypothalamus to the pituitary gland, and from there to the adrenal glands, which prepare you for an emergency.

  Suppose you walk into the supermarket and, unexpectedly, find yourself being chased by a rhinoceros intent on goring you. You will start secreting CRF within seconds—and for good reason. Corticotropin-releasing factor blocks energy storage, specifically inhibiting the process by which the body stores fat as triglycerides and sugar as glycogen. Instead, energy is diverted in a hurry to the muscles that are hurtling you down the produce aisle. At the same time, CRF dampens appetite, sexual drive, and reproductive processes. These effects are particularly logical; this would be a foolish time to waste energy by ovulating or planning lunch.

  And it is much the same during an infection. Interleukin-1 triggers CRF release, and soon enough neither sex nor food seems particularly appetizing. Levels of sex hormones plummet, and if the illness lasts long enough, then ovulation and sperm production can be disrupted.

  More crummy symptoms can be attributed to IL-1. It makes you sleepy—although no one is quite sure how. And it does something else particularly unpleasant.

  There are nerve pathways coming from various outposts in your body—from the surface of your skin to deep within your muscles and tendons—that carry pain messages to your spinal cord; these messages are then relayed to the brain, which interprets them as painful. Obviously, stepping on a tack is a very painful stimulus: the pathway originating in your toe is going to be activated, and your brain will register pain in an instant. But far more subtle stimuli will not cross a pathway’s activation threshold. They will not be perceived as pain unless the threshold is lowered. And that’s exactly what IL-1 does; it makes the neurons along the pathway more excitable, inclined to react to things they would normally ignore. Suddenly, your joints hurt, old injuries ache again, your eyeballs throb.

  Altogether, that’s quite an impressive array of effects for a chemical that was once thought of only as an immune system messenger. And it’s this very quality that makes interleukins unpleasant to use as treatments for illness. Potentially these chemicals could help you fight disease by stimulating your immune system. But such a treatment is guaranteed to make you feel crummy. Cancer patients who have been given IL-2, a close relative of IL-1, have felt stupendously sick.

  Biologists have learned a bit about just how IL-1 triggers these crummy symptoms. The chemical binds to receptors on the surfaces of those neurons that play a role in perceiving pain, regulating temperature, and releasing CRF. That, in turn, switches on the synthesis of prostaglandins, compounds that act as signals inside the cell to change temperature set points and sensitivity to pain messages. So potentially, you could decrease a lot of the symptoms of feeling crummy if you took a drug that blocked that prostaglandin synthesis. Which is just what is accomplished by aspirin.

  One major aspect of the sick syndrome still needs to be explained: cachexia, or the wasting away of body weight. This is an obvious thing to happen during a sustained illness, given what happens to your appetite. But cachexia defines something more. During a chronic illness you lose weight even faster than can be explained by decreased eating. Your body has trouble storing energy.

  Corticotropin-releasing factor appears to account for some of that. Recall your desperate flight from the rhino in the supermarket: during such an emergency you need energy for your muscles at that instant, not later, and CRF, as we saw, indirectly blocks energy storage. But CRF also causes stored energy to be released, returning fuel in the form of fat and sugar to the bloodstream. Thanks to IL-1 and hormones such as CRF, the same thing happens during an infection; if it goes on long enough, you lose your fat stores and begin to waste away.

  But cachexia is also
caused much more directly. When a noxious agent is first spotted in the body, macrophages secrete a second cytokine along with IL-1. In addition to its role as an immune system messenger, this cytokine blocks the ability of fat cells to store fat. Reasonably enough, this chemical has been dubbed cachectin.

  Looking at such a wide range of effects, it seems difficult to argue that feeling crummy is something that just happens for no good reason. Clearly, the body works very actively to bring those symptoms about. Various brain regions have evolved receptors for IL-1, and fat cells have developed specific mechanisms for responding to cachectin. Your body is working in a very complex and specific way to make sure you feel awful and waste away when you are sick. What could be the use of that?

  Some of the symptoms make sense. A showdown with a virulent pathogen can require as much energy as a showdown with a rhino. It is no small task to trigger the massive proliferation of immune cells needed to mount a defense against infection: cells must divide and migrate at a tremendous rate; cytokines and antibodies must be hurriedly synthesized and secreted. All this immune activity does not come cheap; it requires a great deal of instant energy. Thus it is quite helpful for CRF and cachectin to block energy storage and keep fuel readily available. It is also quite logical to inhibit reproduction if you’re sick, since producing offspring is one of the most expensive things you can ever attempt with your body, especially if you are female—you’re better off using the energy to fight the disease. If the disease is going to be around for a while, it is a particularly inauspicious time to get pregnant anyway.