An Epidemic of Absence

A New Way of Understanding Allergies and Autoimmune Diseases

Moises Velasquez-Manoff

• Publisher: Scribner
• Year: 2012
• ISBN:
  9781439199404
• Topic: Scienze biologiche
• Subtopic: Biologia

A brilliant, groundbreaking report on the dramatic rise of allergic and autoimmune disease, and the controversial therapies scientists are developing to correct these disorders. From asthma to Crohn's disease, everyone knows someone who suffers from an allergic or autoimmune disorder. And if it appears that the prevalence of these maladies has increased recently, that's because it has—to levels never before seen in human history. These days no fewer than one in five—and likely more—Americans suffers from one of these ailments. We seem newly, and bafflingly, vulnerable to immune system malfunction. Why? One possibility is that we have systematically cleaned ourselves to illness; this belief challenges deeply entrenched notions about the value of societal hygiene and the harmful nature of microbes. Yet scientists investigating the rampant immune dysfunction in the developed world have inevitably arrived at this conclusion. To address this global "epidemic of absence, " they must restore the human ecosystem.This groundbreaking book explores the promising but controversial "worm therapy"—deliberate infection with parasitic worms—in development to treat autoimmune disease. It explains why farmers' children so rarely get hay fever, why allergy is less prevalent in former Eastern Bloc countries, and how one cancer-causing bacterium may be good for us. It probes the link between autism and a dysfunctional immune system. It investigates the newly apparent fetal origins of allergic disease—that a mother's inflammatory response imprints on her unborn child, tipping the scales toward allergy. An Epidemic of Absence is a brilliant, cutting-edge exploration of the dramatic rise of allergic and autoimmune diseases and the controversial, potentially groundbreaking therapies that scientists are developing to correct these disorders.

CHAPTER 1

Meet Your Parasites

Mother, it is no gain, thy bondage of finery, if it keep one shut off from the healthful dust of the earth, if it rob one of the right of entrance to the great fair of common human life.¹

—Rabindranath Tagore,
Bengali poet and Nobel laureate

One chilly November morning, I head south from San Diego in a bottom-tier rental car. The standard journalistic paraphernalia—a digital recorder, camera, notepad, and pencils—accompany me in the passenger seat, as well as directions to my meeting point: the last exit before Mexico. I also have a printout of my recent blood work, proof that I’m not anemic, not infected with hepatitis or HIV—that I’m healthy enough for the coming experiment.

As I drive, the radio announcer conducts a gruesome tally of the most recent violence in Tijuana, where I’m headed: two bodies hung from a bridge, a third decapitated, a fourth shot. More than this terrible, ongoing brutality, however, parasites occupy my mind—worms that migrate through flesh, burst into lungs, crawl down throats, and latch on to tender insides. Any traveler might fret over acquiring such hangers-on while abroad. But I’m heading to Mexico precisely to obtain not just one, but a colony. Today in Tijuana I’ll deliberately introduce the hookworm Necator americanus—the American murderer—into my body.

And for this dubious honor, I’ll pay handsomely—a onetime fee of $2,300. If I receive twenty of the microscopic larvae, that’s $115 apiece for a parasite that, in the early decades of the twentieth century, was considered a scourge on the American south. Some worried—without condescension, I should add—that hookworm was making southerners dim-witted and lazy, that it was socially and economically retarding half the country. And photos of poor, worm-ridden country folk from the time—followed by their robust health after deworming—clearly show the dire costs of necatoriasis, or hookworm disease: jutting collarbones, dull eyes, and listless expressions on wan faces. They appear as if consumed from the inside.

Hookworm has mostly disappeared from the U.S., the result of protracted eradication efforts in the early twentieth century. But in the usually poor, tropical countries where it’s still endemic, it can cause anemia, stunt growth, halt menstruation, and even retard mental development in growing children. Between 576 million and 740 million people carry the parasite. And for all the aforementioned reasons, public-health types consider worm infections a “neglected tropical disease.” Helminths, as they’re called, are not as obviously fatal as malaria, say, but their constant drag on vitality is insidious. The parasites keep children from learning in school. They prevent parents from working. Some argue that they contribute to the self-reinforcing cycles of poor health and poverty that plague entire nations.

So why am I considering acquiring this terrible creature? Scientists have two minds about parasites these days. Some consider them evil incarnate, but others note that while the above-mentioned horrors are sometimes true, the majority of humans infected with parasites today—upward of 1.2 billion people, or somewhere between one-fifth and one-sixth of humanity—host worms with few apparent symptoms. This camp has begun to suspect that worms may, in fact, confer some benefits on their human hosts.

As early as the 1960s, by which time hookworm had been largely eradicated in the U.S., scientists puzzled over the lack of symptoms in some. “Well-nourished persons often harbor helminths without apparent damage,” remarked one physician in 1969.² “One may question the wisdom of treating such infections, especially with chemotherapeutic agents with toxic qualities.”

Decades of plumbing the mechanisms that allow one creature to persist within another, a clear violation of the self-versus-nonself rules thought to govern immune functioning, has taught immunologists much not only about how wily worms really are, but also about how the human immune system actually works. Parasites like hookworm were ubiquitous during our evolution. Might our bodies anticipate their presence in some respects, require it even? And might some of the more curious ailments of modernity result partly from their absence?

That brings me to my motive: A large and growing body of science indicates that parasites may prevent allergic and autoimmune diseases. And I’ve got both.

* * *

When I was eleven, my hair began falling out. My grandmother first noticed it. I was visiting my grandparents at their beach house that summer when, one afternoon, she called me over, examined the back of my head, and proclaimed that I had a nickel-sized bald spot. Then we all promptly forgot about it. With the sand, waves, and sun beckoning, it just didn’t seem that important.

But by the time school started a few months later, the bald patch had grown. A dermatologist diagnosed alopecia areata, an autoimmune disorder. My immune system, normally tasked with protecting against invaders, had inexplicably mistaken friend for foe, and attacked my hair follicles. Scientists didn’t know what, exactly, triggered alopecia, but stress was thought to play a role. And at first glance, that made sense. My parents were in the middle of a messy, drawn-out divorce. I was also beginning at a new junior high school that fall; I had, it seemed, much to worry about.

I also had other, better-known immune-mediated problems. I suffered from fairly severe asthma as a child, and food allergies to peanuts, sesame, and eggs. (Only the egg allergy eventually disappeared.) At least once yearly, usually during seasons of high pollen count, my wheezing became so severe that my lips and fingernails turned blue, and my parents had to rush me to the emergency room. There, doctors misted me with bronchodilators, or, during severe attacks, pumped me full of immune-suppressing steroids.

“Aha!” said the dermatologist when he learned of these other conditions. There was a correlation among allergies, asthma, and alopecia, he explained. No one was sure why or what it meant, but having an allergic disease like asthma increased one’s chances of developing alopecia.

Years later, I would learn that the co-occurrence of these two disorders was likely evidence of a single, root malfunction. But at age eleven, I accepted on faith that where one problem arose, so, probably, would others. So what to do? Given my age and the relatively small size of the bald spot, the doctor recommended watching and waiting. Alopecia usually corrected itself in time, he said. So we waited.

In a month, another bald spot appeared, on the right side of my head. Then one on the left. Seemingly overnight, a large one opened up just above the middle of my forehead. As more hairless patches appeared, the pace at which new ones emerged accelerated. Every morning, my mother combed and gelled my hair into place to hide the growing expanse of denuded skin; but soon, concealing my bare scalp became nearly impossible. The spots began to converge. I was going bald.

We returned to the dermatologist. This time, he had a less upbeat assessment. The more the disease progressed, he noted, the less likely recovery. The odds worked like this: Only 1 to 2 percent of the population got alopecia areata at all, a bald spot or two that, after a time, usually filled in again.³ But for a significant minority, maybe 7 percent of those with alopecia areata, the hair loss became chronic. Some progressed to alopecia totalis, total loss of hair on the head. At that point, the chances of a full recovery diminished substantially. Whatever mistake the immune system had made, it became permanent. And of this totalis subset, some went on to develop alopecia universalis—loss of hair on the entire body. For them, recovery was nearly impossible.

None of this sounded good, especially as I was speeding toward totalis and—who knows?—universalis after that. Two treatment options existed, neither of which worked without fail: immune suppression or irritation. Steroids suppressed the immune response and, basically, called off the attack dogs, allowing hair to grow again. Immune stimulation, on the other hand, worked in slightly more mysterious ways. Inflammation induced by an irritant distracted the immune system from less pressing projects, such as attacking hair follicles. Irritation would earn my hair follicles a reprieve. As neither approach was a sure bet, the dermatologist recommended that I try both.

I did, and neither worked—although I developed an oozing blister where I applied the irritant. My alopecia advanced until, by age sixteen, not a single hair remained on my body. I had joined the elite ranks, somewhere around 0.1 percent of the population, of those with alopecia universalis. I put on a hat, which I’d wear more or less nonstop until my early twenties, and tried to get on with my adolescence.

* * *

Not until my thirties did I look into what scientists had discovered in the roughly twenty years since that first bald spot appeared on my head. I wasn’t too hopeful; surely, I would have heard had a cure been developed. As I contemplated having children, I’d begun fretting about what lay hidden in my genes. The first genome-wide association study of alopecia, published in 2010, showed that the disorder, the most common autoimmune disease in the U.S., shared gene variants with several much worse autoimmune diseases, such as rheumatoid arthritis, type-1 diabetes, and celiac disease.⁴ Soon thereafter, my first child, a girl, arrived. Now the results of my investigation had concrete applications. If alopecia suggested a tendency toward immune malfunction, and if that tendency was modifiable, I wanted to know how to better play the cards. I wanted to ensure that my progeny remained free of both allergic and autoimmune disease.

I was right about one thing. Treatments for alopecia hadn’t advanced much since my childhood. They still consisted mainly of irritants and immune suppressants, and as neither approach corrected the underlying malfunction, both would require indefinite use. Prolonged exposure raised a host of secondary concerns. Repeated steroid shots, for example, were not only exceptionally painful, they thinned and discolored the skin. Irritants induced swelling, redness, and skin flaking. One powerful immune suppressant called cyclosporine increased the risk of skin cancer. No thanks.

However, the patterns of immune-mediated disease in general caught my attention. The incidence of both autoimmune and allergic diseases had recently increased, and to the degree that scientific literature conveys feeling, in this case it evinced alarm. Scientists threw around the word epidemic to describe the rising prevalence of asthma especially, a descriptor usually reserved for infectious diseases, like the prayer-inducing, body-wasting, dead-in-a-day cholera epidemics that terrified the world during the nineteenth century. Generally speaking, however, there was no asthma bacterium, no autoimmune virus. No new plagues were driving this particular pandemic. Instead, we seemed newly vulnerable to immune dysfunction.

If I possessed glasses that afforded me the power to see otherwise non-apparent allergic and autoimmune diseases, I’d be struck by the sheer abundance of people with these problems. Walking down Broadway in New York City, for instance, one of every ten children passing by would have asthma; one in six would have an itchy rash and sometimes blisters—eczema.⁵ One of every five passersby would have hay fever. If I could see allergic antibodies directly—immunoglobulin-E—I’d note that half the crowd around me was sensitized to dust mites, tree pollen, and peanuts, among other basically harmless proteins. I’d see pockets full of inhalers, and bags stuffed with allergy medicines. In the satchels of the most severely afflicted, I’d see pills of powerful immune suppressants, such as prednisone. I’d even see a few soon-to-be corpses; about 3,500 people die yearly from asthma attacks.

Americans spend perhaps $10 billion yearly on asthma-related drugs and doctor visits. Direct and indirect costs of asthma combined reach about $56 billion. I’d see these funds flowing from allergic and asthmatic wallets to doctors and drug companies. And I’d observe money not flowing from days missed at work, diminished overall productivity, and opportunities lost over a lifetime.

If I took the same walk with glasses that allowed me to see autoimmune diseases, I’d note that one in twenty passersby had one of eighty of these often debilitating conditions.⁶ One of every 250 people—it would take about a minute standing in a place like Times Square for such a person to pass by—would suffer from debilitating pain in his or her intestines, what’s called inflammatory bowel disease.⁷ I’d see scarring and constriction. And in the most severe cases, I’d observe removed lengths of intestine, colostomies (surgically created exits for intestinal contents), and colostomy bags (containers for the effluence) hidden under clothes.

Of every thousand passersby, I’d note one struggling to move legs or arms. These people have multiple sclerosis, a progressive autoimmune disease of the central nervous system. Their vision might blur when they read signs. Their legs might fail to cooperate when crossing the street. The worst cases, of course, wouldn’t be out at all. They’d remain at home, perhaps in electric wheelchairs, maybe bedridden.

I’d note glucose monitors on one of every three hundred children frolicking in Central Park’s playgrounds, children afflicted with autoimmune diabetes, which is usually childhood-onset.⁸ Their skin would bear needle marks from the daily insulin injections required to avoid coma and death.

If my glasses came with headphones, I’d hear a cacophony of worry and desperation: asthmatic teenagers wondering if they’ll be able to join friends in a game of baseball; more severe cases focused on walking slowly, so as not to lose breath; eczematics reminding themselves ceaselessly not to scratch, or if they’ve already scratched, berating themselves for the raw mess left behind.

Those with inflammatory bowel disease might be preoccupied with the pain, sometimes dull, sometimes sharp, that has characterized life since diagnosis. If it’s not racking cramps on their minds, they’ll likely be strategizing around bowel movements, which arrive all too frequently and with a painful urgency, and which sometimes contain blood. Those with MS might be wondering: How much longer before I can’t walk? And everyone will regularly ask: Why can’t doctors fix this? Where did this come from? Why me?

The National Institutes of Health estimate that between 14.7 and 23.5 million Americans have an autoimmune disease, or 5 to 8 percent of the population. The American Autoimmune Related Diseases Association puts the number at more than double that—50 million Americans. In the U.S., autoimmune disease ranks among the top ten killers of women. And that speaks to an omission I made for simplicity’s sake in the above scenario. Roughly three-quarters of those afflicted with autoimmune disease are female. When I had my autoimmune glasses on, in other words, I’d be seeing mostly women.

Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases, once estimated that the direct and indirect costs of autoimmune diseases reached a staggering $100 billion yearly. (By comparison, we spend $57 billion on cancer and $200 billion on cardiovascular disease.) That may seem high, but bear in mind that autoimmune diseases, which are chronic in nature, generally strike in the prime of life, and require decades of costly symptom management.

These statistics apply to the richest countries in the early twenty-first century. But immune-mediated diseases weren’t always this prevalent. Early hints of immune dysfunction during the late nineteenth century notwithstanding, the allergy and asthma epidemics gained steam during the 1960s, accelerated through the 1980s, and then plateaued by the early 2000s. In that period, depending on the study and the population, you’ll find somewhere between a doubling and a tripling of asthma and allergies in the developed world.

Some autoimmune diseases show even more dramatic increases during the late twentieth century. A 2009 study found that the prevalence of undiagnosed celiac disease, a type of inflammatory bowel disease incited by proteins in grains, had increased more than fourfold since the mid-twentieth century.⁹ The incidence of multiple sclerosis has nearly tripled. And for some of these diseases, there’s no end in sight. The incidence of type-1 diabetes, which more than tripled during the late twentieth century, is estimated to double again by 2020.

What has happened? In 2002, the French scientist Jean-François Bach published a seminal paper for anyone asking that question.¹⁰ The study, which appeared in the New England Journal of Medicine, had two graphs side by side, one showing the gradual decline since 1950 of once-common infectious diseases—hepatitis A, measles, mumps, and tuberculosis—next to another showing, over the same period, an increase of autoimmune and allergic disease in the developed world. Nearly everyone contracted mumps and measles in 1950. By 1980, almost no one did. Vaccines had almost eliminated both viruses. In an even shorter period—since 1970—new case...