Chimera

Faith, Madness, and Spontaneous Human Combustion: What Immunology Can Teach Us About Self-Perception

Last Thursday, one of those gray fall days when the starlings gather up and string between the elms around here, my first wife, my children's mother—dead ten years—walked into a pastry shop where I was buttering a croissant. She ignored me, which she always does, ordered a plain bagel and an almond latte, picked up her food, and without a glance at me, walked out. The starlings chittered, the day frowned, and I went back to buttering my croissant.

Just after her suicide, I saw this woman often—in towns where she never lived, walking her Airedales in the park, eating poached eggs at Joe's Cafe, sweeping grass clippings from her walk on Myrtle Street, stepping off the Sixteenth Street bus. I caught her smell while walking beside redbrick arches where she and I never walked. I heard her laughing beneath the birches in the park.

We get together less often now. But when we do, like this morning, her image is as vivid as it ever was—her dark eyes as bright, her odd smile just as annoying.

I'm not crazy.

I know it isn't her, this woman I see and hear and smell. After all, she's dead, and I myself gave her ashes to my son. So it is another, a stranger, transformed by some old film still flickering through the projector inside my head. Just someone with a crooked nose like hers, or her perfume. Someone walking with her knees turned in a little too far. Someone else. I know that. But still, every time I see her, it takes all that I have to stay in my chair, or my car, hold on to myself and not run after her calling out her name.

Some of this I understand. When something or someone is suddenly stripped from us, it seems only natural that our minds would try to compensate. Minds do that. If they didn't, we might ourselves be sucked into the vortex. That part I grasp. I'd have thought, though, that in a year or two, the films in my mind would fade and break, and the tear in my life would close and scar like any other wound. And I expected, as the fissure closed, that my first wife would disappear.

Faith, Madness, and Spontaneous Human Combustion: What Immunology Can Teach Us About Self-Perception Chimera

I was wrong. Ten years after her death, she's still inside of me somewhere.

All the pieces of human bodies fit (more or less) into eleven systems—endocrine, musculoskeletal, cardiovascular, hematologic, pulmonary, urinary, reproductive, gastrointestinal, integumentary, nervous, and immune. So there's a limited number of places where someone could hide something inside a human being. And so far as we know, only two of the body's systems— immune and nervous—store memories, fourth birthdays, or former wives. That narrows it even further.

Most of us don't associate immune systems with hopes and fears or emotions and recollections. Most of us don't imagine anything other than lymph—the pale liquid gathered from the blood—is stored inside of thymuses, spleens, and lymph nodes. The business of immune systems is, after all, not hope, but immunity—protection against things like measles, mumps, whooping cough, typhus, cholera, plague, African green monkey virus; you name it.

But immune systems do remember things, intricate things that the rest of the body has forgotten. And the memories stored inside our immune systems can come back—like my first wife— at unexpected moments, with sometimes startling consequences.

My grandmother had a penchant for saving things. She grew up in a very poor family and believed nothing should be wasted. On the plywood shelves of her closets, mason jars that once held apple butter or pickled tomatoes were filled with buttons, snaps, paper clips, and strips of cloth; seashells, rubber bands, pebbles, bobby pins, and cheap shiny buckles— everything she'd ever come across that she thought might be useful someday.

Immune systems do that, too, believe that most everything they come across will be useful again someday. My grandmother used mason jars, immune systems use lymph nodes. My grandmother gathered beads and hat pins, string and sewing needles—the stuff that fell through the cracks. Immune systems collect bacteria, parasites, and funguses, proteins, fats, sugars, and viruses—the stuff that falls through the cracks in our skin.

Human skin is like nothing else in this universe. It tastes of the sea salt and the iron inside of men and women. Its feel arouses us. Skin is cream, sand, teak, smoke, and stone. Skin is Poetry, music, literature, the dreams of boys and men, girls and women. Skin is all of that, all at once. But mostly, skin is what keeps us apart from everything else on this planet, especially everything that might infect, infest, pollute, putrefy, and possess us. First and foremost, it is our skin that allows us to be here as individual men and women in a hungry world, Skin keeps things out—things that would eat us for lunch. And skin keeps things in—things we couldn't live without.

But skin breaks down, gets punctured by knives and needles or scraped off by tree limbs and tarmac, gets cracked, burnt, and broken. When that happens, if it weren't for our immune systems, we'd die—abruptly. Immune systems deal with the things that crawl through the holes in our skin. Immune systems label the intruders as dangerous, round them up, and destroy them. And immune systems remember the things they've seen beneath our skin, because immune systems believe that one day those things will be back.

That's why we get to be adults—immunological memory. It's also why vaccines work. Until a few years ago, children in this country were regularly injected with cowpox, also known as vaccinia virus. Vaccinia virus is very similar to the virus that causes smallpox, with one important exception. Vaccinia virus doesn't cause the disfigurement, illness, and often death smallpox virus causes in humans. But as Edward Jenner discovered in the 1700s, people (in Jenner's case, milkmaids) who had been infected with cowpox didn't get smallpox. A miracle. Immunity to cowpox protects a child from smallpox. That's because even though their personalities are very different, smallpox virus and vaccinia virus have a lot of physical features in common. Immune systems that have learned to recognize and destroy cowpox virus also recognize and destroy the look-alike smallpox virus before it can do harm.

Immune systems remember most of those miracles, too, often for a lifetime. A child vaccinated against smallpox virus makes a more rapid and specific response on a second encounter with that virus than does an unvaccinated child. And the rapidity and specificity of that second response is what saves the vaccinated child's life.

A simple memory of a tiny virus, but a memory powerful enough to have ended the devastating disease of smallpox on this planet. Immunological memory, but in essence no different from the memory that pulls our fingers from the flame a little faster the second time, or the memory that guides the cleaver beyond the scars on our knuckles, or the memory of a first love lost.

The way immune systems remember is extraordinary. Just beneath our skin, there are specialized cells called Langerhans cells. Langerhans cells grab up bits of whatever drops through the holes in Our skin—bacteria, viruses, funguses, and so on. And Langerhans cells do this very well. After we are wounded, Langerhans cells begin to gather up the things that crawled in through the tears in our fabric. Then the Langerhans cells make their way to the nearest lymph node. Lymph nodes are little peanut-sized filtering stations strung throughout human bodies. There are literally thousands of lymph nodes in the average man or woman—lymph nodes under our arms, in our necks, beneath our jaws, on top of our intestines—just about everywhere. So there is always one near any hole we manage to punch in our skin. When the Langerhans cells reach those nearby lymph nodes, they hand off bits of what they've collected to another group of cells called T-helper cells. T-helper cells are a type of white blood cells called lymphocytes, and T-helper cells control all the operations of the immune system. Once they see the junk carried to the lymph nodes by the Langerhans cells, the T-helper cells tell another group of white blood cells called B cells to begin making antibodies. Antibodies are proteins that bind specifically to things like viruses and bacteria and help to destroy these invaders. But some of the antibodies made during an immune response do something other than destroy invaders. These antibodies stick to the surface of another specialized cell in the lymph nodes. These cells, called follicular dendritic cells, are to lymph nodes what green glass mason jars were to my grandmother.

The antibodies stuck to the surfaces of follicular dendritic cells also begin to gather pieces of the invader or invaders and hold them there in the lymph nodes. Those bits of viruses and bacteria and funguses do all kinds of things. Most importantly they don't let us forget what has just threatened us. Follicular dendritic cells and the bits of antigens bound to them help us re. member by maintaining a low-grade, barely perceptible immune response against the pieces of the invader inside of our lymph nodes. Then, the next time the same virus or bacterium shows up beneath our skin, that smoldering immune response quickly flares into a systemic immune response—one that is much faster and much more specific than our response the first time we were threatened by this virus or bacterium. Because of that, a second exposure to many infectious diseases is much less likely to be life-threatening.

That—the newfound specificity and speed of the second and subsequent immune responses to the same threat—is immunological memory, and it's as powerful as any memory in the brain. This whole process—from skin to lymph node to follicular dendritic cell—happens each time we are infected, So, after each infection, a few of the bacteria or viruses that infected us are saved in the lymph node where they first arrived, saved on the follicular dendritic cells. By the time we're adults, our lymph nodes—like my grandmother's mason jars—are filled with bits of things we've been infected by: viruses, bacteria, parasites, proteins, lipids, carbohydrates. Just how long lymph nodes hang on to these things isn't altogether clear. But it is clear that lymph nodes keep things for quite a while, maybe even for a lifetime. Lymph nodes are the repositories of our infectious histories: over there's a piece of that flu I had last winter, and beyond that there's a bit of tetanus left over from when I was bitten by a mouse, and here in the foreground is some of the polio vaccine I got when I was six, and behind that lymphocyte—there just below the high endothelial venule—there's another flu virus from an infection I don't even recall, and so on. Just like an attic before the garage sale. But unlike my grandmother, every day, our immune systems sort this growing mass of memorabilia and remind themselves of what they've seen before and what they are likely to see again—memories, infectious memories. Things we mustn't forget.

Mustn't forget, but mustn't hold too close to the surface, either. Just like some of the memories lurking in Our brains, an ill-timed immunological recollection can hurt or blind us, sometimes even kill us. These memories we must suppress.

Some of the viruses and bacteria stored on follicular dendritic cells appear to be intact and alive. As long as they are there, the only thing keeping us from having the same diseases all over again is the constant vigilance of our immune systems. Through that vigilance, all of those things hanging around inside us are kept in check, suppressed to the point where they can help us remember, but cannot cause, disease. Memory with a mission, selective recollection and suppression.

But lots of things can distract immune systems: drugs, malnutrition, stress, hormones, age, infection. When these things happen, immune systems can forget about all those deadly things packed away inside of us. Then, like minds in panic, immune systems may get confused, forget which memory to recall and which to suppress, and the past can flare inside of us.

When that happens, our very survival depends on our ability to regain our balance, enhance some recollections, and suppress others. No one knows how humans do this.

And it isn't just our immune systems that store infectious memories. Nervous systems hold dangerous biological recollections as well. A particularly pernicious example of this is shingles, a severe chicken pox-like rash that usually appears across the ribs beneath the arms but also may grow in eyes and lungs. Shingles occurs most often in the elderly.

People don't get shingles unless as boys and girls they were infected with chicken pox. Shingles and chicken pox are caused by the same virus—varicella zoster virus. When we get chicken pox, our nervous systems, and perhaps our immune systems, collect live varicella zoster viruses. Later, when age or illness or depression distracts our immune systems or stresses our nervous systems, or both, some of these viruses begin to multiply again. Then varicella zoster may blind us, even kill us. This is shingles— a blazing memory of a childhood disease, chicken pox, a thing we wish we could forget.

And there are many others: like cytomegalovirus that causes pneumonia, Epstein-Barr virus that causes mononucleosis, nasopharyngeal carcinomas and lymphomas; adenoviruses that cause acute respiratory diseases like pneumonia, leukemia viruses, some parasites, tuberculosis, HIV (human immunodeficiency virus), and likely many more that we haven't yet discovered. All of them smoldering inside of us, inside of lymphocytes and macrophages, inside of lymph nodes, inside of neurons, waiting for a moment when our immunological backs are turned.

So immune systems, as well as nervous systems, are filled with memories—vivid, painful, sometimes fatal. The fragments of a life lived, bits and pieces of the past. And sometimes, immune systems lose control of this smoldering wreckage and old flames flare anew. Is there a woman, then, living in this ruin, a woman inside of me who walks and speaks exactly like my first wife?

It is, of course, impossible to answer that question. No one understands nearly enough about wives or immune systems. But it isn't an entirely stupid question. Among the things we regularly trade with our wives (and the rest of our families, for that matter) are viruses—colds, flus, and cold sores, to mention only a few.

Enveloped viruses—like those that cause flu, cold sores, and AIDS—are so named because they carry with them an "envelope" of lipids and proteins taken from the host cell (the cell they grew up inside of). Each time we give our flu to our wives or our cold sores to our husbands, we also give them a little bit of ourselves. And when our husbands or our wives get hold of those bits of us, they don't just discard them, they pack some of them away inside their lymph nodes. Pack them away, sometimes for the rest of their lives.

Other viruses move DNA between people. Retroviruses— viruses like HIV—store their genetic information in RNA instead of DNA. When these viruses infect human cells they first make DNA from their own RNA. Most retroviruses then insert these DNA copies of their RNA genomes into the chromosomes of the cells they infect. Sometimes, when new retroviruses are made, these viruses may take with them not only viral genes but pieces of human chromosomes as well. When an infected person later passes the virus to someone else, occasionally some of the first person's DNA gets incorporated into the second person's chromosomes. That means that each time one of us is infected with a virus like this, we also acquire some of the DNA, some genetic piece of the person who infected us. Currently, virologists know of only a few retroviruses, and all of these viruses, like HIV, cause significant human disease.

But the sequence of the human genome reveals many more retroviral sequences than can be accounted for by the few retroviruses we know of. One percent or more of all the DNA inside Of humans came from retroviruses. So infections involving retroviruses may be much more common than we currently imagine. Maybe, then, we exchange bits of genes with one another a lot more often than we realize. And there is now evidence that some of these exchanges swap DNA from within the major histocompatibility complex—the segment of the human genome that is most directly involved in immunological individuality, most directly involved in the biological definition of self. Infection becomes communication, memorization chimerization. At once something fanciful, something mythical, something oddly immunological that leaves each of us holding tightly to pieces of others inside our genetic heart of hearts.

Maybe that seems trivial—a bit of envelope here, a little DNA there. But over the course of an intimate relationship, we collect a lot of pieces of someone else. And a little of each of those pieces is stored on the follicular dendritic cells inside our lymph nodes, and a little of that DNA gets into our chromosomes.

Until. Until the person we've been communicating with is gone, and we stop gathering bits of someone we love. For a few days or weeks, everything seems pretty much like it was. Then one day, for no apparent reason, our defenses slip just a little, and a ghost walks through the door and orders an almond latte.

Apart from a few viruses inside of neurons, nervous systems don't appear to store memories in the same ways immune systems do. Most neurologists and neurochemists believe that memory within the nervous system involves something called long-term potentiation, or LTP—a means by which certain nerve pathways become potentiated or preferred.

Every nerve signal that comes to the brain has hundreds, perhaps thousands, of different pathways that it may choose to follow. The path the nerve impulse chooses determines the outcome of the signal—whether we flee or fight, for example. At the head of each of those possible paths there is a gate, called a synapse. The key to the gate is carried by molecules called neurotransmitters-—things like norepinephrine and glutamine, dopamine, and acetylcholine. The first time that "two plus two" enters a brain, it may stimulate no response at all; or it may stimulate the release of norepinephrine and cause a recollection of the sound a toy train makes; or it may stimulate acetylcholine release and cause a vision of a ballerina. But after being consistently rewarded for only the word "four" and a vision of four oranges, the gate—the synapse that leads to four oranges—becomes potentiated. Now each time this person hears "two plus two," she responds, "equals four." That's long-term potentiation. In return for it, we get to move on to second grade.

Some of this potentiation we learn, like two-plus-two; and some of it we are born with, like eating when we are hungry. Beyond that, a lot remains to be learned about how nervous systems store and recall memories. A whole lot.

Some neurologists have divided human memory into two broad categories; declarative memory (explicit, consciously accessible memory, e.g., What was the name of the cereal I had for breakfast?) and implicit or emotional memory (often subconscious and inaccessible, e.g., Why was I so frightened by that harmless snake I saw today?). Both of these forms of memory appear to depend on long-term potentiation. But there is evidence for a third kind of memory as well, something I'll call phantom memory. Memories that come from someplace beyond or below declarative and emotional circuits. Whether phantom memories depend on long-term potentiation is unclear.

I'm pretty confident that declarative memory had nothing to do with my first wife walking in on me as I was buttering my croissant last Thursday. I'm less certain about emotional memory. I am deeply intrigued by phantom memory.

People who have had arms or legs removed often experience phantom limbs—a sensation that the arm or leg is still there, sometimes a very painful sensation. This feeling is so real that people with phantom hands may try to pick up a coffee cup just as you or I would. People with phantom legs may try to stand—before their declarative minds remind them they have no legs. Always, the missing limbs seem completely real to these people and as much a part of themselves as any surviving appendage even when the phantom limb is a foot felt to be dangling somewhere below the knee with no leg, real or phantom, between the ankle and a midthigh stump.

Some of those who have studied phantom-limb sensations argue that these are only recollections of sensations "remembered" from the days before amputation. But children born without limbs—children who've never experienced the sensations of a normal foot or hand or leg—experience phantom limbs. Clearly, these phantoms are not simple recollections of better days. Instead, the presence of phantom limbs in children with no real-limb experience suggests that some sort of prenatal image—some template of what a human should look like—is formed inside our fetal minds before our arms and legs develop, before even our nervous systems are fully formed. And this behavior in these children further suggests that if long-term potentiation is involved in phantom memory, then these particular nerve synapses become potentiated well before birth, well before development of the human form is even completed inside the womb. If, at birth, our bodies don't fit this template, don't match our potentiated circuits and the imagery those circuits create in our minds, our brains try to remake reality, twist it until it looks the way our minds say reality ought to look.

It isn't clear where phantom memories reside. Because phantom limbs are often exceedingly painful, physicians have tried to locate the source of the phantom sensations and eliminate them. Spinal cords have been severed, nerve fibers cut, portions of the brain removed. Sometimes, some of these procedures caused the pain to disappear, but it usually returned within a few months or years. And none of these treatments routinely caused phantom limbs to disappear.

Occasionally, some phantom limbs do disappear on their own, though almost never permanently. Nearly always the phantoms will return—in a month or a year or a decade. And when they do, they are just as real as the day they first appeared, or disappeared.

Phantom memories aren't always memories of limbs, either. People who've lost their sight describe phantom visions—not recollections of something they once saw, but detailed images of places they have never been—buildings, burials, forests, flowers. Similarly, some people who've lost their hearing are haunted by complex symphonies blaring in their ears-—symphonies that no one else has ever heard. Beethoven was among those who suffered from such phantom sounds.

It is impossible to say how much of our reality comes to us from the physical world that surrounds us and how much "reality" we create inside our own minds. If, using a machine like a PET (positron-emission tomography) scanner, we were to analyze all of the nervous activity occurring at any given moment inside a human body, no more than a fraction of a percent of this activity would be directly due to input from the senses. That is, only a tiny portion of what our nervous systems are occupied with—and by inference only a tiny portion of our thoughts—results directly from what we see, hear, taste, smell, or touch. The rest of it, the remainder of our mental imaging, begins and ends inside of us.

How that affects our reality isn't clear. But it is clear that much of what originates within us is powerful—powerful enough to fill our mental hospitals with people who see and hear things that the rest of us would say aren't there. Among the sights and sounds that originate within us are our images of ourselves and our realities. Such images are powerful icons, nearly immutable. These are the images of our dreams, our poetry, our theaters, our psychoses. Some of these we are born with. Others take us years to acquire and assemble. In the end, intermixed with the rubble of the archetypical images we began with, there is a picture of us and the world around us—one that suits us and probably only us.

But, if physical reality—the outside world—changes abruptly, it may not be within our power to so abruptly change such deeply rooted images of ourselves and our worlds. A loved one, after years together so nearly a part of us, suddenly and unexpectedly dies. A career of thirty or more years is abruptly terminated by downsizing. Childhood memories that no one can speak of. When that happens, reality itself becomes implausible. Often, our minds can't handle that. At that point, there are only two ways out—madness or a reconstruction of reality. What determines the difference between these two options may be nothing more than the degree to which our reconstruction of reality fits with other humans' visions of reality. At any rate, the only way to staple our imagined realities and "real" realities back together is with a phantom, a bit of virtual reality that reconciles our world and the real world, a stitch to close the void. Our loved one reappears at unexpected and sometimes inappropriate moments, a phantom we have projected onto others to make our reality fit our need. Our stories about who we are change suddenly to fill holes that have opened in our pictures of ourselves—ephemeral patches to mend inner reality. Our past becomes someone else's past, our reality a fiction. Gaps between the hard facts of the real world and the truths we hold inside threaten us. Because we must, sometimes we fill those gaps with ectoplasm.

Are the dead, then, living within my neurons—inside of my own pictures of me?

Images of ourselves—some, apparently, older than we are—are obviously deeply etched into the stones of our minds. These are powerful things that resist change, particularly sudden change. But even the aboriginal portraits of ourselves aren't without seams or cracks. Inside those seams and between those cracks, small forces working over years can introduce change. Time, time in an intimate and powerful relationship, could reshape even our images of ourselves. The changes would be little ones at first—a tiny fissure unmortared here or there, room to include in our self-portraits parts of other men or women, a first vision of ourselves as something more. In the beginning, perhaps, nothing more than the turn of a phrase—one we've admired from the first in the speech of the one we love—now turning up more and more often among our words.

Later, larger pieces of us might be lifted and replaced by whole chunks of another. Husband and wife begin to speak alike, know what the other is thinking, anticipate what the other will say, begin, even, to look alike. Until one day, what remains is truly and thoroughly a mosaic, a chimera—part man, part woman, part someone, part someone else.

Later, if that man or that woman is amputated from us, clipped as quickly and as cleanly as a crushed leg, our minds are suddenly forced into a new reality—a reality without the other, a reality in which an essential piece of us is missing. At that point, our declarative minds would be at odds with our own pictures of ourselves. To rectify that, to reconcile the frames flickering inside with the darkness flaming outside, we conjure a phantom, a phantom to change our world. We force a bit of what is inside outside, out into the real world. We create someone or something that will help us slow the universe for a moment while we repaint our pictures of ourselves—repaint, with a very small brush, a very large canvas.

There is a painting by Pierre-Auguste Renoir which I first saw at the National Gallery in Washington, DC. This painting, titled Girl with a Watering Can, is filled mostly with the off-whites and intense blues of the impressionist painter. But in the girl's hair, there is a blood-red bow. I've often wondered about that bow and why Renoir put it there. I've imagined the bow was a symbol of the death that begins at each of our births; I've imagined it as an omen of sexual maturity—its pain and its promise; I've even imagined it was nothing more than a schoolgirl's red bow.

But just now, I think the red bow is the other one inside of us, the red one who is probably at first mother—physically, immunologically, and psychologically. The one, too, who is later so many others—grandmother, friend, severed limb, or lost wife.

Renoir placed the bow in the girl's hair, near her brain. I don't imagine, though, that by that placement he intended for us to ignore all the other spots where bits of men and women gather in us.

Sitting on the redwood deck behind my house this morning, the air smells of cinnamon and rainwater. For reasons I can't recall, those smells remind me of the Brandenburg Concertos, coffee on Sunday mornings, and the intricate paths of swallows.

Somewhere inside of me, there is a woman. But where she lives and who it was that led her into that pastry shop last Thursday, I've no way of knowing. For one part of me, that ignorance is a gnawing blindness. For another part of me, it is enough to simply know for certain that I will see her again.