The Invisible Kingdom: Reimagining Chronic Illness

by Meghan O'Rourke

As Susan Sontag pointedly observes in Illness as Metaphor, illnesses we don’t understand are frequently viewed as manifestations of inner states. The less we understand about a disease or a symptom, the more we psychologize, and often stigmatize, it.

It took years before I realized that the illness was not just my own; the silence around suffering was our society’s pathology.

To the degree that my quest had an object, that object turned out to be learning to live with uncertainty and incapacity.

To have a poorly understood disease is to be brought up against every flaw in the U.S. health care system; to collide with the structural problems of a late-capitalist society that values productivity more than health; and to confront the philosophical problem of conveying an experience that lacks an accepted framework.

It was easy, in those years, to feel that a lack of dietary discipline played a role in my exhaustion, because I could tell that certain foods made me feel worse, leading me to assume responsibility for my own unwellness. I toggled between the conviction that something had to be wrong—I didn’t feel OK—and the conviction that I was to blame, and if I just stopped eating sugar, or pizza, say, I’d be fine.

Like many in their baby boomer generation, they saw doctors as unquestionable experts. You didn’t go to them unless you had a high fever or a bad fall or a wound that needed stitching. In that case, you got a diagnosis, you took medicine or had surgery, and you got better, more or less in that order. But if the doctor told you nothing was wrong, nothing was wrong.

I read when I am worried, and when I got home that’s what I did. I read whatever I could find about autoimmune diseases on the internet; I ordered books from the NYU library; and I downloaded papers published in medical journals. My ability to accumulate information felt like the only control I still possessed.

Even the term “autoimmune disease” may be imprecise: it is not known in every case whether autoimmune dysfunction is the cause of the disease or a consequence of it.

Today, the Autoimmune Association (also known as AARDA) estimates that as many as 50 million Americans live with autoimmune disorders, which would make it one of the most prevalent categories of disease, ahead of cancer.

For reasons that are still not well understood, approximately 80 percent of autoimmune patients are women, though a handful of autoimmune diseases overwhelmingly affect men.

According to AARDA, it takes an average of three years (and four doctors) for a sufferer to be given a diagnosis of an autoimmune disease. One reason is that early symptoms can be intermittent and nonspecific. Then, too, a limited amount of autoimmunity itself is not necessarily considered pathological: tests often show the presence of small numbers of antibodies to your own tissues. “Autoimmune disease” is what happens when such autoantibodies produce sustained harm to your body. In some ways, the distinction between normalcy and pathology is arbitrarily defined—as well as hard to measure.

In fact, medicine still lacks good diagnostic tools for many autoimmune disorders (which is why many research institutes are at work trying to improve them). As Noel Rose told me, tests often show the presence of disease only when 80 percent of the organ under attack has been destroyed. By that time, as he put it, “The train’s gone off the tracks.”

As it is, many clinicians assume that the patient, who is often a young woman, is simply one of the “worried well”: people who visit doctors for reassurance that nothing is wrong with them.

My fatigue felt like a problem with me—something about my very being. I worked too hard, but without enough discipline; I exercised, but I ate junk food; I was sloppy where I should be ascetic. When I felt off, it was my fault, a sign of some internal weakness, a lack of moral fiber, a crack running through the integrity of my being.

I don’t know what to do, I feel like I am no longer living but just existing and miserable because I feel so sick.

me, I decided to embark on a diet that many people online were enthusiastic about. It was a version of the autoimmune Paleo diet, which looks a lot like the so-called Paleo regimen: no gluten, no refined sugar, little or no dairy, lots of organic meat and vegetables, but also no eggs or nightshade vegetables. The goal of the diet was to fix any underlying “gut flora dysbiosis”—an imbalance of good and bad bacteria in your gut—and begin repairing the gut by allowing the mucosal wall that lines it to heal.

cheap.) I fretted over whether it was OK to eat raw spinach, given that it may be goitrogenic (suppressive of thyroid function); hot peppers, because they’re a nightshade vegetable; or eggs, because they contain lysozyme, an enzyme that—well, it’s complicated.

Autoimmune diseases have biological markers, but they come and go, and patients’ flares can be exacerbated by stress.

“The tendency in many parts of medicine is, if we can’t measure it, it doesn’t exist, or the patient is cuckoo.”

“Pain is always new to the sufferer, but loses its originality for those around him,” Alphonse Daudet observes in In the Land of Pain. “Everyone will get used to it except me.”

Knowledge brings the hope of treatment or cure. And even if there is no cure, a diagnosis is a form of knowing (the word “diagnosis” derives from the Greek gignōskein, “to know”) that allows others to recognize our experience and enables us to tell its story. I felt acutely the absence of a story I could tell others. Without a story, who—or what—would help me get better?

Medicine treats women differently from the way it treats men, as Barbara Ehrenreich and Deirdre English show in For Her Own Good: Two Centuries of the Experts’ Advice to Women, and gender has real implications for medical care—mostly negative ones, if you’re a woman. Until recently, most medical research was performed almost exclusively on cisgender men and male animals. A 2011 study found that male mice were overwhelmingly used in four fifths of the fields studied. Researchers do not include female mice in their studies, The New York Times noted, because of concern that “the hormonal cycles of female animals would add variability and skew study results.” And so research has failed to consider differences in male and female biology, including disparities in how people of different sexes respond to pharmaceutical drugs—due to variations in metabolism, body fat percentages, and enzyme activity. Low-dose aspirin lowers the risk of heart attack in men, but it has no impact on heart disease risk for women under sixty-five. Beta-blockers may place women with hypertension at a greater risk of heart attack, a 2020 study found. (The authors conducted the study after realizing that women were historically underrepresented in clinical studies of beta-blockers.) Women have more complications from anesthesia. In 2001, the Institute of Medicine published a report called Exploring the Biological Contributions to Human Health—Does Sex Matter? “It matters,” the report concluded, “in ways t...

The innate system we are born with is our first line of defense, responding immediately to pathogens and foreign matter, deploying natural killer cells and phagocytes like macrophages and neutrophils—types of white blood cells—to fight off pathogens, frequently by ingesting or engulfing them. Acquired (also known as “adaptive”) immunity is our second and more sophisticated line of defense: it mounts a response specific to the pathogen encountered, and then remembers those pathogens. Adaptive immune cells include B cells and T cells, which help fight off infections in concert with our innate immune system. The primary organs of the immune system, I learned, are the bone marrow and the thymus, a soft, pinkish-gray triangular gland above our heart. (It resembles a thyme leaf, hence its name.) It is one of the few organs that grows smaller after puberty, the point at which many of our immune cells have been made. In the bone marrow and the thymus, hordes of B and T cells, named for the parts of the body from which they come, are born and educated. Both kinds of cells attack infections, heal wounds, and more. B cells make antibodies: Y-shaped proteins that target specific pathogens by locking into them in ways that bring the video game Tetris to mind. Each antibody is specific to a given pathogen; measuring them gives doctors a record of the body’s encounters—the body’s memory of the foes it has faced.

With my instructors’ tutelage, I came to see the immune system as a kind of college where so-called naïve immune cells grow up and—as if choosing a major—are trained to focus on a specific foreign substance. When our adaptive immune cells meet their first antigen, or bit of foreign matter, they go through structural and chemical changes. Imprinted by that antigen—as if via a kiss, Caleb said, drawing a picture of an antigen and antibody interlocked—the naïve immune cell becomes an enemy specific to it. (This is the premise behind most vaccines: they contain an altered version of a virus, to make the body produce antibodies designed specifically to lock into it.) T cells known as “T-helper cells” (technically, CD4+ T-helper lymphocytes) help ramp up the immune response in the body, stimulating B cells to produce antibodies and stimulating T killer cells, which can kill cells infected by virus. Autoimmunity and allergies occur when immune cells mistakenly identify as pathogens things that are not threats (the thyroid, the liver, pollen, cat dander) and an immune response ensues, possibly because of what is known as “molecular mimicry.” Your immune system, in trying to attack a pathogenic Epstein-Barr virus protein, ends up attacking similar-looking molecules in the body.

Immunology uses the term “regulation” to describe the body’s mechanisms for calling its army of immune cells back and turning off their destructive power. As Caleb put it one day, in a metaphor I would find repeated elsewhere, “The T cells are like cadets, sent out to attack viruses. But they have little self-control, and so they are monitored by sergeants, known as ‘regulatory T (Treg) cells,’ who tell them the attack is over and it’s time to head back to the base. When the regulatory T cells aren’t working, you get an out-of-control immune response, making you sicker than you need to be.” One reason people feel sick when they have an infection is that the inflammatory response of the immune system itself makes them feel sick—something I had failed to understand previously. (This is also why many people feel briefly sick after getting, for example, a COVID-19 vaccine—a vaccine, after all, is designed to provoke an immune response.) The cell that has found a virus or bacterium uses chemicals called “chemokines” and “cytokines” to recruit an inflammatory response, calling for white blood cells. These chemicals work on a gradient—like a radar signal that gets stronger and louder a...

The word “inflammation” comes from the Latin verb “inflammare,” or “to set on fire,” and it evokes the heat and redness that come with the rush of cells to a wounded or attacked area. The process is beneficial when the body deploys it appropriately, as in response to an injury. But in the long term, inflamm...

As she put it, the microbiome (whether in our gut or in other organs and tissues or, indeed, in our mouth) and our immune system are like a kindergarten class and a teacher. The class is orderly when the teacher—the immune system—is present. But if the teacher leaves the room (in this case, to fend off a virus), the normally well-behaved pupils get unruly, and the biome may misbehave. Now everyone is drawn into the bad activity, releasing chemical signals that almost appear to egg others on. As she noted, “P. gingivalis is the biggest cavity-driving pathogen. A lot of people have it in their mouth, and they are fine. But if your immune system isn’t great, and fails to monitor it, P. gingivalis starts to produce biofilm-signaling molecules, and neighboring organisms are like, wait, we can join a biofilm?” (Biofilms are slimy structures inside of which bacteria live in an organized community and communicate with one another; the spongy molecular matrix that contains them helps protect them from the immune system’s attacks.) And soon you’ve got a mouth full of cavities.

But the question remains: why do women make up approximately 80 percent of people with autoimmune diseases? An answer may lie in the replicated X chromosome (which allows for a genetic mutation to happen twice) or in the role estrogen plays in regulating the immune system. Women generally have a stronger immune response to infections and vaccines than men do. (Consider the fact that men are more likely to die from COVID than women.) Studies suggest that estrogen interacts with the adaptive immune system’s B and T cells in ways that predispose it to become more “autoreactive.” One review of the literature on autoimmunity noted that “many autoimmune disorders tend to affect women during periods of extensive stress, such as pregnancy, or during a great hormonal change.” Studies have identified links between endocrine transition states in women and the development of lupus, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, among others; the reproductive years, medical school teaches, put women at risk for autoimmune disease, perhaps due to the hormonal changes during and after pregnancy. During the decade surrounding menopause, studies show that women are at higher risk for developing some kinds of autoimmune diseases. Levels of anti-inflammatory cytokines decrease, and pro-inflammatory cytokines increase.

Autoimmune disease is a case of mistaken identity: The line between self and non-self becomes blurred. . . . Symptoms are the body’s cry for help. Telling you to replace anger with love isn’t some soft, New Age philosophy. Studies show that negative emotions increase inflammation, so if you’ve been mad at your body for years, it’s in your best interest to start practicing forgiveness.

Today, the idea that chronic stress makes us ill—that our thoughts and experiences can, in a scientifically plausible way, alter our physiology to the point of introducing disease—is an accepted one. Chronic stress releases continual jolts of stress hormones, which can raise blood pressure and cause cardiovascular disease, leading to a hardening of the arteries. It makes gut-related illnesses like irritable bowel syndrome worse. And it can lead to dysfunction in cortisol production.

Decisions like this are often portrayed as products of the patient’s credulousness, her naïveté. But the reality is that many of us are people who, faced with no good choice, shrug our way into the hands of those we don’t trust in search of help.

The next day, I began deleting my writing files. I went online to my financial accounts and checked that I had labeled beneficiaries for each. I sat with my computer and went through file by file, deleting spare files, then went to the cabinet where my journals were kept. I hesitated, then piled them on a corner of the office shelving to bring out later with the garbage. It is hard to write about this time, but it would also be false to suggest that my illness had not at this point—two and half years into feeling that I had the flu every single day—led to despair about whether I could go on, without at least the prospect of my suffering being seen. For those weeks, I felt the depression at one’s state that many chronically ill people confront at some point in their illness. (Research suggests that roughly one third of people with a serious medical condition experience symptoms of depression.) In no way do I think, or want to suggest, that depression was the root cause of my symptoms or my illness. Rather, in retrospect it is painfully clear that the invisibility of my illness was one of the most challenging parts of my suffering, wearing my resilience down over time. I have always been a social person who thrives on deep connection with others. Like many type-A personalities, I was willing to work extremely hard, and accommodate myself to a great deal of pain, if a doctor just told me what to do and expect, or if I knew that my illness was being meaningfully researched. Bu...

Years later, pregnant with my first son, I had a terrible allergic reaction to a medication I was taking, and my skin became scaly and inflamed, from my face to my feet. Everyone who saw me said, “That looks miserable,” and doctors rushed to relieve my symptoms. “You must be very uncomfortable,” one said. “Poor thing,” volunteered another. But this rash, as terrible as it was, was nothing compared to what I had felt when I was at my most ill. The difference was that none of these symptoms could be seen. The illness was severe but invisible. And that invisibility made all the difference—it made me invisible, which itself almost killed me.

There is a razor-thin line between trying to find something usefully redemptive in illness and lying to ourselves about the nature of suffering. Until we mourn what is lost in illness—and until we have a medical community that takes seriously the suffering of patients—we should not celebrate what is gained in it.

To be chronically ill is to be in a state of ever-present “camouflaged grieving,” as the historian Jennifer Stitt puts it. It was this ever-present grief I felt was being swept under the rug when my friend counseled me to see the good that had come of my illness. She wasn’t wrong that something had come of it—but her quick counsel negated the complexity of the quest.