Authors: Donna Jackson Nakazawa
All of which begs the question: Are there 1,200—or more—silent, hidden Buffalos spread across America, where residents simply haven’t yet thought to ask why they’re being struck by these debilitating diseases at disturbingly high rates? Since the majority of patients take years to be diagnosed, we have no records of who has autoimmune diseases in America, and studies linking specific autogens to the triggering of autoimmune diseases are relatively new and all too easily dismissed by industry, chances are that in most communities where such clusters surreptitiously exist no one is even asking the question.
SEARCHING FOR A FRESH START
Today, LaShekia Chatman and her mom, Renita, live in the more economically prosperous community of Cheektowaga, not far from downtown Buffalo, in a brick house with wrought iron fencing—identical to every other house on their street. The Chatmans moved out of East Ferry four years ago, hoping for a fresh, chemical-free start—only to find that they had relocated to the vicinity of yet another autoimmune-disease cluster in the making. Soon after the Chatmans moved in, the local Cheektowaga Homeowners Association released a report citing high incidences of autoimmune diseases in their community. Residents and environmental scientists from the University at Buffalo believe that several chemical-laden landfill dumps and the Buffalo Crushed Stone Quarry, which surround the neighborhood in what some refer to as a “toxic triangle,” are predisposing Cheektowaga residents to autoimmune illnesses. Mine blasting at the quarry throws large amounts of crystalline silica, one of the most documented triggers of lupus, rheumatoid arthritis, and scleroderma, into the atmosphere. Hydrogen sulfide, a toxic ingredient in mining wastewater, races through the area creeks.
When the Cheektowaga cluster became public through the work of local activists, LaShekia said it hit her like “an anvil striking someone in the head in a cartoon with the balloon: ‘Are you
KIDDING
me? Not
AGAIN
.’” Having jumped from one frying pan into the next, the Chatmans understandably feel it might do little good to move elsewhere in Buffalo. Who knows what hidden toxic waste they might end up living near next time?
Today, LaShekia, who has since graduated from college and begun work on a novel, has spent nearly a decade and a half battling a total of five different devastating autoimmune diseases, two of which—lupus and scleroderma—can bring normal existence to a halt, or even end a life. Still under Alan Baer’s care, she manages her illnesses on a finely tuned combo cocktail of prednisone, Imuran, Plaquenil, Prilosec, and aspirin. At the age of twenty-nine, she confesses she sometimes feels lonely and “envious” watching other young people enjoy the normal things that twenty-somethings with their whole lives ahead of them do. She longs to be like them, to “be able to think about having a career, getting married, and having children,” she says. “Or even just to get to be irresponsible and stay out late with friends and eat junk food and go dancing all night, because you don’t have to do the super-responsible things that someone with a chronic illness has to do, like get plenty of rest, go to bed early, eat right, and watch your every move.”
After speaking many times by phone, LaShekia and I finally meet for the first time on a beautiful, crisp August day in Buffalo. The sky is a photogenic blue with bottlebrush marks of white—an optimistic backdrop for a city where the streetscape exudes a gray and downcast feel that, by comparison, would make a Hopper painting seem cheerful. Judith Anderson is driving LaShekia and me on a whirlwind tour through LaShekia’s past—starting with LaShekia’s old jump-roping ground, on the street where she first lived. The small colonial in which LaShekia once lived in the community of Delavan-Grider lies a ten-minute stroll from 858 East Ferry and a three-minute walk from the TCE site on Delavan. As we drive slowly through her old neighborhood, LaShekia, a stately young woman sporting a chic chignon and hip black cat glasses, points through the car window to the car manufacturing plants and abandoned brick smokestacks of factories rising along the landscape in every direction—a kind of industrial ghost town.
For a moment we linger in the car outside her old house, and I can imagine LaShekia racing on lanky legs up and down these front steps as a child, full of vigor and promise. “How does it feel, looking back at growing up here?” I ask.
“I feel this rush of shock and anger that this cluster could develop without any of us knowing what was happening to us, or why,” she says. “The fact is, if I had grown up, say, in Colorado, this wouldn’t have happened. I hate to think of other teenagers living in industrial towns who might have to forfeit everything because other people have decided that cleaning up chemical waste isn’t important.”
The stew of environmental contaminants in which Buffalo residents and their children have marinated for years clearly has tipped many of their immune systems toward disease. Each individual’s unique combination of genes, gender, hormones, exposure to environmental chemicals and heavy metals, and viral hits determines his or her future. In many patients like LaShekia, it may well be that environmental chemicals first torque the immune system so that it sits just a hair trigger shy of becoming deranged. Suddenly, one last hit occurs; a virus enters the system and an autoimmune reaction is spurred into motion.
LaShekia lived in an area with waste sites containing TCE, PCBs, and lead—all known or suspected autogens—her entire life. After fifteen years of her immune system’s being taxed in a slow and continuous manner by the toxic agents that surrounded her, a seemingly harmless, common virus, Epstein-Barr, attacked. The point at which LaShekia’s immune system could continue to maintain balance was suddenly breached, and her immune cells raced out of control. The role that viruses play in reaching this final point is, as we are about to see, also emerging as a critical factor in today’s autoimmune-disease crisis.
T
here may be no better example of how a common virus can trigger the body to sabotage itself than my own story. In the past seven years, a slew of viral attacks have changed my body permanently. The first incident occurred in 2000, when I was sidelined by a flu with the usual fever and muscle aches and pains, the kind of virus from which most people quickly recover to get on with their lives. A few weeks after the flu had come and gone, however, the skin on my forearms, hands, calves, and feet became curiously numb—as if the surface of my skin had fallen asleep and only half awakened. The strange deadened feeling was accompanied by odd shooting pains in my fingers and wrists, like sparks of fire spreading from one hot nerve to the next.
The first doctor I saw, a local internist, suggested my symptoms might be related to the fact that I have a pacemaker. He thought there might be a connection between my heart problems and the tingling and numbness in my extremities. My cardiologist, however, scoffed at the idea. He referred me to Dr. Ahmet Hoke, a well-known neurologist at Johns Hopkins, who ordered biopsies in which pencil-eraser-deep tissue samples were taken from my thighs. Hoke, a Middle Eastern–born physician who serves as the director of the Division of Neuromuscular Diseases at Johns Hopkins, discussed my test results with me a few days later. My biopsies showed that I had suffered damage to my small-fiber sensory nerves, the tiny nerves that tell us whether what we touch is soft or rough, hot or cold. The disease, known as small-fiber sensory neuropathy, was, he elaborated, “probably the result of a recent virus.”
“How does a virus attack my nerves?” I wanted to know.
“An autoimmune reaction,” he said. “Most likely a protein on the surface of a molecule of the virus you had looks like a protein on the surface of the molecules of your nerve tissue. The body gets tricked by their similarity and attacks the small-fiber sensory nerves as it fights the virus. We call it molecular mimicry.”
It was the first time—in that summer of 2000—that I fully grasped precisely what “autoimmune” meant. Our immune cells could mistake our body’s own tissue for a virus or bacteria or other foreign invader, or antigen, and the mechanisms by which the immune system should prevent such cases of mistaken identity from happening could fail abysmally. I had always known, theoretically, that hypothyroidism, which I also had, was autoimmune in nature, but I had never fully understood before how autoimmunity actually occurred within the human body.
Hoke reassured me that, in my case, my biopsies showed that something quite hopeful had occurred. In some patients with small-fiber sensory neuropathy, the nerves, after degenerating, regenerate to some degree. My sense that my skin had fallen asleep and only partially reawakened was more accurate than I could have known.
Small-fiber sensory neuropathy would turn out to be the least distressing of the three autoimmune reactions I would experience over the next six years—each of which Ahmet Hoke would tie back to infections I’d had a month or so prior to the episode. In 2001, and again in 2005, after having had a seemingly innocuous bout of vomiting, I developed Guillain-Barré syndrome, or GBS, and became paralyzed as my immune system systematically damaged the myelin sheaths that coated my nerves, the same sheaths that are injured in multiple sclerosis.
Once again my immune fighter cells were flubbing up, making similar molecular mistakes—each time with more disturbing consequences.
Yet something puzzled me. Although a virus had triggered each of my autoimmune episodes, I knew that viruses had to be only part of the story. I had had many feverish flus prior to the one in 2000 that led to small-fiber sensory neuropathy. And I had had many stomach flus in my life prior to 2001. While I clearly possessed the genetic predisposition to autoimmunity, and, yes, a virus had attacked, these two factors had been true for me many, many times before, yet I had never demyelinated and undergone the “flaccid paralysis” of Guillain-Barré syndrome after having had the stomach bug. Clearly, like most people who develop autoimmune disease after a virus, something else in my environment had to have been slowly pushing my immune system to this precipice—a precarious edge from which one viral hit could send me tumbling, like Jill, all the way down the hill. Nevertheless, in my case—as well as for the majority of patients with autoimmunity—keen attention had to be paid to the catalytic role of viruses in my disease and the astonishing manner in which viruses are somehow able to pull that final switch that tricks the immune system into attacking the cells of the body it is meant to safeguard.
THE LUPUS HUNTERS
For decades, researchers investigating Guillain-Barré syndrome have held the suspicion that GBS might be linked to infectious pathogens—not only because patients so often report having been ill in the six weeks prior to getting the disease, but also because clusters of cases have been linked in timing and locale to large, national vaccination programs with vaccines containing viral antigens. Yet the idea that autoimmune diseases as a broader group might be triggered in part by viruses has been anathema to most researchers.
Ironically, the first scientists to emerge with startling lab evidence that lupus might be triggered by a ubiquitous virus almost all of us are exposed to by adulthood was a professor and grad student team that wasn’t even looking to make that connection.
Dr. John Harley, a transplanted West Virginian whose dry, quick humor and deep smile wrinkles soften his exacting edge, today manages a research staff of two hundred as chief of the Arthritis and Immunology Research Program at the Oklahoma Medical Research Foundation (OMRF). Most days he can be found more or less racewalking through the halls of his research institute as he moves between his research lab, teaching classroom, and the hospital, often shadowed by a handful of students and an assistant towing a cart full of files. Harley also serves as a professor and chief of the Rheumatology, Allergy and Immunology Division at the University of Oklahoma Health Sciences Center and as a staff physician at the Oklahoma City VA Medical Center, where he cares for patients with lupus and other autoimmune diseases.
For the past thirty-two years, Harley has committed himself to pinpointing the first step that goes awry in the pathway that leads patients to develop lupus. He has deep personal reasons for pursuing the triggers for the disease. When Harley was working toward his MD/PhD at the University of Pennsylvania three decades ago, his best friend at Penn died of lupus. They were working together as senior lab partners when his friend’s kidneys began to shut down. Harley, who often stopped by to visit his friend at the hospital in the evenings, found him lapsing in and out of consciousness one night, suffering from kidney failure. Although treatment for lupus has not progressed much in the intervening decades, there were even fewer options for lupus patients in 1974, even at Penn, considered one of the best hospitals in the world. That night, Harley held his friend to comfort him. Not long after, his friend died in Harley’s arms.
Nearly twenty years down the pike, by the early 1990s, Harley—after a residency at Yale and postdoc training at the National Institutes of Health—was in charge of the large-scale lab operation at the Oklahoma Medical Research Foundation, where he had been working for eight years. Judi James, meanwhile, was a fourth-generation Oklahoman from Pond Creek, a small northern Oklahoma town of fewer than nine hundred people, who’d come to OMRF as an undergraduate and never left. The first student of the newly established MD-PhD program at the University of Oklahoma Health Sciences Center, James wanted to pursue research in asthma. Unable to find a lab dedicated to asthma research, she headed to Harley’s lab to get experience “so that I could move on to asthma research” later on. Then she had an encounter that shifted her career focus forever. One morning she accompanied Harley on rounds at University Hospital and “met a woman with lupus in the intensive care unit who was exactly my age—twenty—who was extremely sick. She had two small children. I was struck that we still lacked anything but broad immunosuppressants to help her and that we knew so little about the disease, or what triggers it.” In an instant James was caught, she says, “by the lupus research bug.”
Harley and his lupus team were already engaged in exceedingly meticulous work trying to isolate potential triggers for lupus. All cells have many proteins contained within them. Such protein molecules are, in turn, made up of sequences of amino acids. These amino acids make up specific, codelike patterns and are present in—or sometimes on the surface of—our body’s cells, as well as in the foreign invaders that enter our bodies, be they viral or bacterial. Each sequence of amino acids forms a unique pattern, something like the bar codes on supermarket items that the scanner in the grocery store recognizes as you go through the checkout line. Let’s say a flu virus enters your body. Immune cells that are programmed to recognize the proteins from the flu virus set out to find it and attack it. They are able to recognize these proteins as dangerous because they recognize the unique code of amino acids on the surface of the virus.
Once these immune fighter cells recognize the flu virus based on its similar “identification bar code,” they send out a posse of antibodies that begin to bind with the intruders, often engulfing and destroying them.
But in a less than healthy body—one compromised by genetic predisposition, a heavy burden of chemicals, stress, a processed-food diet, or some combination thereof—the immune fighter cells and the antibodies they send forth begin to make costly mistakes. They may see a set of amino acids, or a bar code, in healthy body tissue that is very like those in the flu virus, and instead of recognizing that pattern as being similar yet distinctly different, they goof, mistaking the sequence of amino acids in the healthy body cells for those belonging to the infiltrating germ. They set out to obliterate all the cells and viruses that share the same sequences, just to be sure they are getting the job done.
Such was the case in my own episodes of neurological autoimmunity. The fighter cells of my immune system mistook the amino acid sequence in the proteins of my own healthy myelin sheaths for a similar amino acid sequence in a foreign stomach virus and attacked both in the process of trying to scourge the flu from my body. When such a scenario occurs, autoimmune disease strikes.
Broadly speaking, this drama of mistaken identity is what Harley and James suspected was happening inside the bodies of lupus patients. They knew that some antigen out there had a sequence of amino acids—or bar code—very similar to that found in lupus patients’ healthy cells. They knew this because they could identify a key sequence of eight amino acids in the actual structure of lupus patients’ autoantibodies. “Autoantibody,” the word scientists use to designate antibodies that have attacked and bound with healthy tissue in error, literally means “antibody against self.”
This particular string of eight amino acids, taken by researchers from what is known as the “Sm B amino acid sequence” was bound by the autoantibodies of lupus patients. It existed as a kind of smoking-gun evidence after a crime. Harley suggested James look at the sequence more closely. By looking at its structure, Harley hoped he and James might be able to peer into the past and see what pattern of amino acids on a foreign antigen so closely imitated the pattern of eight amino acids in the Sm B sequence that it could cause lupus patients’ immune systems to err, triggering the whole cascade of events leading to lupus.
Still, he wasn’t overly hopeful. There were literally thousands of potential antigens out there.
Yet what Judi James found was startling. James searched a database of similar amino acid sequences in hopes of finding a clue as to what might be a potential lupus antigen. She showed Harley that this Sm B sequence bore a striking resemblance to an amino acid sequence that researchers had previously identified in the Epstein-Barr virus.
Epstein-Barr virus, or EBV, is a common viral infection that ordinarily causes anything from low-grade fever and sore throat symptoms in children to mononucleosis in teenagers and adults. When Harley saw that the sequence of a part of EBV was so similar to the Sm B amino acid sequence, “bells went off in my mind,” he recalls. “I thought that if that’s really right, that would be really tremendous.” If they knew the virus did trigger the disease, could they intervene to stop it? At that point the connection remained just a virtual experiment—portrayed only on a computer screen—and Harley knew the match might have occurred as a coincidence and not show causation.
Besides, the question of whether EBV might play a role in lupus was, for any researcher of Harley’s ilk, a scientific hot potato, one best left untouched. Years earlier, researchers had wondered if there was a link between Epstein-Barr and autoimmune disease. Scientists had studied the Epstein-Barr–autoimmune connection in the early 1970s—in the news headline heyday of Epstein-Barr—and found, by and large, nothing there. That seemed to make sense—after all, by age forty 96 percent of people have been infected with Epstein-Barr, a member of the herpes family, while only a fraction develop autoimmune disease. In the world of autoimmune-disease research, the question of whether Epstein-Barr could cause lupus had been asked and answered and the answer was no.
But resuscitate it they did. Harley and James were applying much more sophisticated lab techniques than had been available to the scientists in the 1970s. They had actual amino acid sequences in hand to study and compare. Still, Harley was cautious. One doesn’t overthrow a supposedly watertight conclusion of modern science overnight. He asked Judi to replicate her results. Each time, the answer came up the same: it appeared that EBV might indeed play a direct hand in triggering autoimmunity by being a hauntingly close match to the Sm B sequence.