The Autoimmune Epidemic: Bodies Gone Haywire in a World Out of Balance--and the Cutting-Edge Science that Promises Hope (No Series) (6 page)

“People don’t see what lies behind the scenes in most autoimmune diseases,” she says. “Because we go through ups and downs, you might see us on a good day, between severe flares, when we seem to be perfectly fine. You don’t know that we’ve just spent six weeks in hell.” Few can imagine, she adds, that behind her bedroom door even on one of these good days, Kathleen has to take twenty-two medications about an hour before she tries to get up, just so she can handle the pain when her feet hit the floor. “By the time you run into me at the grocery store at two o’clock in the afternoon and say hello to me, I’m ready to nod and say, ‘Oh, I’m fine, how are you?’” Kathleen worries, she says, that because autoimmune disease so often remains hidden from public view, she and other women like her will continue to be stigmatized as malingerers.

A CASE OF BLINDED SCIENCE

How is it that autoimmune diseases have remained so obscure? Why do so many of these diseases go undiagnosed for so long, and why do we have so little comfort and treatment to offer the patients who suffer from them? The answers to these questions require a step back in time, to half a century ago.

The medical age of wonders began seventy years ago, and what an age of miracles it was. When my own grandfather, C. Donald Larsen, a research biochemist and founding member of the National Cancer Institute, served as head of the cancer research grants program at the National Institutes of Health in 1955, he walked into medical laboratory settings every day that, world over, boasted little more than test tubes, microscopes, and Bunsen burners. As a young thirty-eight-year-old scientist in 1939, he had already become world renowned for being the first to demonstrate that cancer-causing chemicals could pass through the placenta and later cause tumors in offspring. Yet his was only one small speck of discovery in the burgeoning age of miracles.

In the span of the next thirty to forty years scientists discovered a range of antibiotics, invented vaccines that would wipe out polio and prevent hundreds of thousands of deaths from rubella and typhus, and America began the war on cancer. Heart surgeons were opening up chest cavities in living patients and transplanting hearts, pacemakers were invented, and neonatal care began to save infants so small it seemed God’s hand had reached down from heaven itself and snatched them from death.

Yet, ironically, during the same time span in which cures for ancient scourges were tumbling out of laboratories, the medical establishment had no idea that autoimmune diseases even existed. Scientists, in general, were clinging to an erroneous presumption that the body’s immune system could not turn on itself; researchers were convinced that an autoimmune response was simply not possible. This presumption—set forth in the early 1900s by Nobel laureate Paul Ehrlich, a charismatic German immunologist who termed this theory
horror autotoxicus
—stood as dogma across the immunology domain for more than half a century.

It would take a young PhD and dedicated medical student to slowly begin to turn the theory of
horror autotoxicus
upside down. In 1951, as a newly minted twenty-three-year-old PhD from the University of Pennsylvania, Noel Rose and his pregnant wife, Deborah, packed all their meager belongings into the back of an ancient, rear-dragging Oldsmobile station wagon and journeyed north from Philadelphia to the State University of New York at Buffalo. Back then, the little-explored and poorly understood domain of immunology—the study of how the immune system functions in the body—was hardly a bustling field, and few labs existed where a young PhD could go to complete his medical studies in the field, much less support a new wife and coming child.

Today Rose, a genteel seventy-nine-year-old whose generous smile spreads nearly as wide as his signature bow tie, serves as director of the Center for Autoimmune Disease Research at the Johns Hopkins School of Medicine and Bloomberg School of Public Health. Back then, Rose considered himself fortunate to receive an invitation from Ernest Witebsky and his immunology team at the University of Buffalo to serve as a junior faculty member. Part of the appeal of moving to Buffalo was the fact that Witebsky was the scientific grandson of Nobel laureate Paul Ehrlich. Ernest Witebsky was a student of Hans Sachs, who, in turn, had been one of Paul Ehrlich’s principal protégés. Witebsky was the inheritor of the Ehrlich mantle and was universally recognized as a vigorous champion of the
horror autotoxicus
theory.

Assigned one part-time assistant and a ten-by-ten office that also served as his lab, Rose set to work. At Witebsky’s request, Rose was seeking to prepare a pure form of thyroglobulin, the major protein of the thyroid gland, in a natural, unadulterated form for use in other experiments Witebsky was busy conducting at the time. Rose had worked with rabbits for years, and all those long hours spent amidst rabbit cages had led him to develop a severe allergy to rabbit fur. He often had to wear a mask in order to help circumvent an asthma attack. Nevertheless, Rose quickly succeeded.

In one of the final steps involved in creating this pure thyroglobulin and assuring it was not altered, Rose injected that thyroglobulin—derived from rabbit thyroids—back into his rabbits. Later, however, when he examined the rabbit thyroids, he was shocked by what he saw. The rabbit thyroids were inflamed—and that should not have happened. They had produced antibodies to the thyroglobulin and developed lesions in their thyroids. Thyroid lesions signaled that the presence of an antigen—a foreign invader that is capable of causing the production of an antibody—had caused the rabbits’ immune systems to turn on and destroy their own thyroid tissue. Almost all of the rabbits had slowly developed a disease that mimicked the human disorder known as Hashimoto’s thyroiditis. Although Hashimoto’s was already a recognized disease in 1951, its cause had remained unknown. That Hashimoto’s might be caused by the immune system attacking the cells of the thyroid was a concept that stood completely at odds with
horror autotoxicus.
Yet in that small postdoc lab, fifty years ago, Rose was staring at proof positive of autoimmune disease—a completely revolutionary idea at the time.

“I sat there for a long time, looking at the results with a mixture of awe and fear,” Rose recalls. “It was one of those marvelous and rare eureka moments in science when you realize that you’re on the edge of an important new discovery. But I was also afraid. I realized that it would be difficult to convince my mentor as well as the world that I was right.”

For the next several years, Rose worked, at Witebsky’s urging, to run his experiments again and again to correct for any possible errors. Finally, Witebsky too became convinced: when an antigen from the thyroid gland was introduced into the body, the body’s fighter antibodies could mistakenly damage the patient’s own cells in devastating blasts of self-sabotage, resulting in thyroid diseases such as Hashimoto’s and hypothyroidism. Together, Rose and Witebsky published their findings.

By 1957, the concept of autoimmune disease was born—though it would be another ten years or more before it was accepted. Yet despite Rose’s startling discovery—and despite the growing number of scientists whose quiet work would, over the next several decades, substantiate his findings—medical schools continued to churn out specialists who were taught
horror autotoxicus
: the body’s immune system could
not
develop an autoimmune response. For Rose, it was a train wreck in the making: while fellow scientists could and should have been ferreting out potential causes for autoimmune disease, no one was even on the case.

It was a classic case of what twentieth-century scientific philosopher Thomas Kuhn once termed “normal science.” Science is conservative in nature, unwilling to abandon ideas without persuasive evidence. The overwhelming majority of scientists accept a single scientific ideology as the starting point from which they form their own viewpoint—the pathway from which they view the entire scientific landscape—to the degree that they cannot overturn that ideology, even if research begins to show that it is blatantly leading them astray.

It wasn’t for another decade that scientists around the country began to wake up—at first one by one, and then in droves—to what Rose and his colleagues had long known: autoimmune responses could be triggered to affect virtually every organ and system of the body. Meanwhile, as this startling autoimmune connection came to light, different groups of specialists quickly scrambled to claim whole sets of diseases as their own. Rheumatologists, discovering that the root cause of rheumatoid arthritis was the body attacking and inflaming its own tissue, claimed arthritis, lupus, and all other joint-related autoimmune illnesses as rheumatologic disorders. Neurologists, discovering that in a whole host of diseases—MS, myasthenia gravis, myositis, Guillain-Barré syndrome—the body was destroying parts of its neuromuscular system, became designated specialists in those diseases. Likewise, bowel disorders—Crohn’s disease, ulcerative colitis, and inflammatory bowel disease—were farmed out to the gastroenterologists.

By the early 1970s autoimmunity was finally an accepted precept—and yet there was no one standing on the mountaintop, looking down at these various specialists’ fiefdoms and seeing how the roads leading to them intersected or asking what the common biological origins or treatments for these diseases might be.

Certainly no one was asking what triggered these diseases. What was wreaking havoc with the intricate inner workings of the human immune system in populations throughout the industrialized world?

In fact, up until the mid 1990s, no one had bothered to figure out how many Americans had an autoimmune disease. Numbers on how many Americans have each type of cancer in each state have been collected by the National Cancer Institute since 1973; the National Center for Health Statistics and the Centers for Disease Control have collected data on cancer since the early 1900s. Yet it was only a decade ago that scientists first began to cast about for a general sense of how many Americans might be afflicted with autoimmune disease. In 1995, Noel Rose approached Virginia Ladd, president of the then fledgling American Autoimmune Related Diseases Association (AARDA), the only autoimmune advocacy organization that encompasses all of the autoimmune diseases, and said, “We have
got
to find the numbers.” Ladd, a small but determined gray-haired dynamo who had founded the organization, was able to come up with only five thousand dollars to fund the project, a paltry sum in the high-roller arena of scientific research. With that, Rose hired a PhD candidate, giving her about a month to ferret out how many patients had each of the twenty-five autoimmune diseases they would be counting. Two years later, Rose’s student came up for air with the astounding statistic that 9 million patients were suffering from those twenty-five autoimmune diseases alone—as many patients as had cancer.

In what is called the epidemiology of epidemiology, Rose and his PhD candidate were able to take those figures and extrapolate to the fifty-five other recognized autoimmune diseases that had not yet been included in their study. They arrived at the figure of 22 million—one in twelve people—who were being taken down by an enemy within. Twenty-two million, for a set of diseases no one was looking at, was a startling statistic.

Since that time, NIH has revised that number to be as high as 23.5 million as more diseases are recognized as autoimmune and are added to the tally. Still, say many advocates, the actual number of patients may be far higher: a recent NIH report states that many autoimmune patients are never properly diagnosed. And existing epidemiological studies on how many individuals have each autoimmune disease have been sparse at best.

One of the more interesting diseases that is not yet officially under the autoimmune umbrella lies in the field of cardiology, where researchers have recently shown that the autoimmune process is deeply implicated in atherosclerosis—the narrowing and hardening of the arteries from the slow buildup of plaque—which is implicated in 1.2 million heart attacks a year. In 2005, Mayo Clinic researchers reported that rheumatoid arthritis patients carry twice the risk of heart failure as other patients. Other studies show similar elevated risk of heart disease among patients with lupus, diabetes, and MS. Researchers believe that some of the genetic variants that predispose a patient to autoimmune disease are the same genetic variants that predispose a patient to heart disease.

Although the exact means by which autoimmune disease is linked to atherosclerosis is only now becoming clear, significant evidence suggests that somewhere in the disease sequence—the cascade of plaque building up on the arterial wall, inflammation, the rise of C-reactive protein levels, and the atherosclerotic plaque erupting—an immune response against the self is involved, just as in autoimmune disease in other parts of the body. Researchers believe that the triggering event may be viral. Recent studies show that in artherosclerosis the body’s immune cells mount an attack against the proteins in a common virus, cytomegalovirus, and in the process become confused, mistakenly attacking the arterial walls themselves.

Michelle Petri, who is involved in a trial to treat lupus patients prophylactically with Lipitor, a potent anticholesterol drug thought to lower the risk of heart attack, says that “the risk is fifty times greater of having a heart attack if you have lupus.”

The concern here extends beyond the autoimmune patients who may develop heart disease. It encompasses those with atherosclerosis who do not know that autoimmunity is involved in their disease and who may be unaware that they are more susceptible to other autoimmune diseases as well.