The Autoimmune Epidemic: Bodies Gone Haywire in a World Out of Balance--and the Cutting-Edge Science that Promises Hope (No Series) (10 page)

(One caveat here for nursing moms: no matter how contaminated breast milk may be, it is still the best food for babies. Not only does bottle feeding pose its own problems because of possible contaminants in the water used to make it, but for reasons we do not fully understand, breast-feeding provides protective measures against diarrhea and ear infections and even some childhood cancers.)

As if all that weren’t enough for Zachary and his family to swallow, there is growing evidence that the sum of chemicals accumulating within us may be more toxic in combination than each chemical is alone. Think back to Becky’s day. Now think of the multitude of trace chemicals such as chlorine, benzene, nitrate, and perchlorate documented to be in the tap water in many areas of the United States (with which Becky makes her cup of tea), the chlorine bleach toilet cleanser, the dry-cleaning solvents in her newly cleaned clothes, the contact cement Becky uses to fix a broken toy, the benzene in the gasoline that she puts into her hybrid SUV, the new wooden pirate-ship climber that Selena clambers on, which has been treated with pesticides, and you can begin to get an idea of the chemical soup that researchers worry is circulating through our bodies.

Recently, scientists from the Environmental Protection Agency wondered whether contaminants that harm the endocrine system might produce a more toxic effect when they act in combination. As it turns out, blends of certain synthetic compounds do create a synergistic effect; two weakly estrogenic compounds create a more potent hit than one compound on its own. The harmful effects of endocrine disruptors are increased two-to threefold when these different chemicals act in unison to block endocrine receptors from normal functioning. Nevertheless, the Environmental Protection Agency is waiting to study the effects of low-dose exposure to endocrine-mimicking chemicals further, believing it “would be premature to require routine testing of substances for low-dose effect.”

However, cautions Silverstone, “We know low levels of chemicals in the environment can cause many negative health consequences, including immune alterations, in animal studies. Funding for research to study these effects is still relatively small. As our knowledge of how the immune system works becomes ever more sophisticated, it seems reasonable to put more research dollars into how subtle alterations of the immune system can be caused by these simple and complex mixtures of environmental chemicals.”

UNDERSTANDING HOW CHEMICALS TRIGGER AUTOIMMUNITY

At what level of contact do humans, versus lab rats, need to be concerned about such environmental hits? This is a question scientists in the field of autoimmune-disease research have attempted to answer only in the past five to ten years. In 2005, researchers from the National Institute of Environmental Health Sciences (NIEHS) and the Lupus Foundation of America cosponsored a meeting entitled Workshop on Lupus and the Environment: Disease Development, Progression, and Flares. This meeting followed on the heels of a 2003 meeting of nine such government agencies to address growing concerns about environmental factors in autoimmune disease. Likewise, a 1998 NIEHS conference also brought together immunologists, clinicians, epidemiologists, molecular biologists, and toxicologists to review current knowledge about links between chemicals in the environment and rising rates of autoimmune disease.

During these three conferences, investigators shared dozens of papers investigating links between industrial chemicals and autoimmunity, as well as data showing how damage is done to the tiniest immune cells by exposure to an array of environmental agents. Scientists linked exposure to compounds such as vinyl chloride—used in making plastic pipes (PVC), wire and cable coatings, and packaging materials—to a higher risk of developing mixed lupus, scleroderma, and rheumatoid arthritis in people. Silica dust, a by-product in ceramic factories, quarries, and construction sites, has also been linked to a higher risk of developing lupus and scleroderma.

One contaminant, trichloroethylene (TCE), a particularly troublesome chemical, received special attention at each of these gatherings. The most common contaminant in Superfund cleanup sites, TCE is a pervasive environmental pollutant that has leached into groundwater through industrial runoff in cities and suburbs across the United States. On military bases, TCE has frequently been used as a cleansing solvent to hose down planes, tanks, trucks, and other machinery, often draining off into streams or groundwater. Other common sources of TCE runoff range from dry-cleaning companies to airplane and machine manufacturers, where TCE is used in stripping metal parts, to leather production, as well as through household use of everything from paint thinners and strippers to many glues and adhesives. (Travel back again through Becky’s day and think of her paint stripping and gluing projects, her dry cleaning hanging on her closet door, and the traces of TCE in the water in her afternoon tea and you get the gist of just how pervasive our exposure to TCE is.)

If you were to visit the National Library of Medicine’s
TOXMAP
online and enter “trichloroethylene,” a diagram of the United States would pop up showing 312 current sites where TCE has been improperly disposed of and where efforts are under way to clean it up—in addition to 360 TCE-contaminated Superfund sites. From Dallas, Texas, eastward, state lines on the U.S.
TOXMAP
are nearly obliterated by overlapping red and yellow dots and white squares, indicating TCE sites in every region. Military sites pose yet another source of contamination: today there are about 1,400 Department of Defense sites where the soil or water is contaminated by TCE. In many locations, especially those with porous ground that allows vapors to seep upward, TCE lingers in the air, particularly inside buildings. (Trichloroethylene is a highly volatile chemical, meaning that, like many chemical particles, it is easily released as a vapor into the atmosphere around us when used in industry or manufacturing.)

One of the most famous TCE hot spots of the past is that of Woburn, Massachusetts, where runoff from area tanneries ended up in the rivers, wells, and the general water supply. The story of the litigation surrounding the site became the basis of the book and movie
A Civil Action
. In other cities, including both Tucson and Phoenix, Arizona, as well as a small community in Georgia—three places where studies have been conducted to date—contamination of the water supply by trichloroethylene has been closely related to cluster epidemics of patients with lupus.

TCE is regularly detected in breast milk, and 10 percent of Americans now have detectable levels of TCE in their blood, from exposure through drinking water as well as breathing it in from the air around us. One of our most significant contacts, however, comes from taking showers. Exposure from breathing TCE released when shower water converts into shower steam is even higher, say experts, than what we get through drinking tap water or breathing TCE. (Exposure rate is so much higher because you are getting multiple types of exposure at once: direct contact with the water at the same time that you are breathing in vaporized TCE from the shower steam.) The National Academy of Sciences recently released a detailed study of how worrisome our daily exposure to TCE actually is, warning that evidence is growing stronger that the chemical is causing a range of disturbing human health problems. Nevertheless, the Department of Defense—which is responsible for cleaning up more than a thousand properties contaminated with TCE—has argued vigorously against the need to change regulations regarding TCE use and cleanup. Senators, including Hillary Rodham Clinton and Barbara Boxer, have appealed to the EPA, writing that TCE is not only a carcinogen but is also known to “damage the nervous and immune systems” and warning that “thousands of Americans may be exposed to unhealthful levels of TCE.” As one epidemiologist put it, “It is a World Trade Center in slow motion. You would never notice it.”

One immunotoxicologist has done much more than just take notice. Dr. Kathleen Gilbert, a forty-eight-year-old associate professor in the Department of Microbiology and Immunology at the Arkansas Children’s Hospital Research Institute in Little Rock and coauthor of much of today’s groundbreaking work on TCE and autoimmunity, has devoted the last decade to helping scientists understand how chemicals like TCE precipitate an autoimmune reaction at the cellular level in the body.

On any given Saturday afternoon, Gilbert’s industrial white-walled and windowless lab on the fourth floor of the Children’s Hospital is humming with activity like the inside of a well-run submarine. Manning the stations are seven scientists—six women and one man. Gilbert, along with her team of graduate students, postdoctoral fellows, and lab technicians—most of them young mothers—can be found here even on most weekends. Although the tools scientists like Gilbert and her team have to understand how autoimmunity is triggered by exposures at the cellular level have improved in recent years, they still remain fairly crude, explains Gilbert, a willowy woman whose sweeping red bangs frame piercing brown eyes. They are crude, she says, “because the field of immunotoxicology itself is still so new.”

So new that ten years ago, when Gilbert first came to the Arkansas Children’s Hospital, few researchers were experts in both immunology and toxicology; indeed, an experienced immunotoxicologist was hard to find. When Gilbert first arrived on the campus as an immunologist, she was immediately approached by a colleague in toxicology to see if she would be interested in collaborating on research on chemical triggers of autoimmunity. Dr. Neil Pumford was curious about whether TCE—one of the most common and pervasive toxicants in our air, water, and soil—might be implicated in autoimmune diseases such as lupus. Pumford’s thought was that he could supply the expertise in toxicology, while Gilbert, who had made a name for herself in immunology while doing her postdoctoral research at Memorial Sloan-Kettering Cancer Center in New York, could supply the immunology know-how.

In 1997, Gilbert was fascinated by the prospect of opening one of the most tightly shut black boxes of modern medical science: she wanted to see in the lab how cellular processes break down when exposed to an environmental toxin. In particular, she wanted to pinpoint what happens when the body, unable to tolerate the toxic load, begins to destroy its own tissue in an autoimmune response.

And that was a tall order. Just to get a sense of how daunting a task that is, consider an imaginary scale of one to ten in which one represents a given environmental exposure and ten represents a person falling ill with an autoimmune disease. If we were to follow each number from one to ten to see how that exposure causes disease in our bodies, we would find that at steps four, five, and six, where we might hope to witness the precise activity of our innermost cells as they turn on self, researchers are still flying relatively blind. While we know from occupational studies that groups of people who are exposed to certain chemicals through their jobs, like those working with TCE-based solvents, have a much greater risk of developing autoimmune disease, we are still unable to see and document the cellular chain of events that causes that exposure to lead to disease. Nevertheless, the quest to make the invisible visible—and demonstrate, in lab animals, how exposure to a particular chemical causes autoimmunity—is the holy grail of autoimmune disease and immunotoxicology research.

The immune response involves one of the most complex systems in the body. Indeed, the number of cell interactions that go into one immune response—say, fighting off the microparticles that come out of a blast of diesel exhaust—would take up three consecutive chalkboards to show in its entirety. Kathleen Gilbert and Neil Pumford, however, have come about as close as anyone in giving us insight into what numbers four and five and six might look like in the human body. They began by working with young adult female mice in their Arkansas lab, to see whether TCE might stimulate an autoimmune reaction in their immune systems. Deliberately exposing human subjects to certain chemicals and waiting to see if they are more likely to develop disease would be clearly unethical, which is why rats and mice have had to stand in place of humans in autoimmune disease research, just as they do in cancer research.

First, they gave the mice drinking water that contained a fairly high dose of TCE. The dose was, in fact, about double what a worker in a dry cleaners or tannery might be “safely” exposed to under standards set by both EPA and Occupational Safety and Health Administration standards. For four weeks Gilbert and Pumford monitored the mice. “We had no idea what kind of immune-system alteration we might see,” says Gilbert. So they did a whole battery of tests to look at what was happening with some of the cells in the mice that would tell them if there was, indeed, an autoimmune reaction.

To understand what they saw, it might be helpful to have one last tutorial on how the immune system functions when T cells—our front line of defense against foreign antigens—start to hunt for, and eradicate, harmful invaders. T cells work together in exquisite collaboration with a vast array of different types of immune cells to protect our bodies from bacterial, parasitic, fungal, and viral infections—as well as from other foreign invaders, including chemicals and toxins. The process starts when special markers—known as antigen receptors, which sit on the surface of T cells—detect pieces of foreign antigens entering the body. When they find an antigen that matches their antigen receptor, they make what you might think of as a bingo match.

To use another analogy, these antigen receptors are like homeland security police on high alert, scouring the body for anything they don’t recognize as safe—anything that is “non-self.” To give you some idea of what a challenging job this policing is, consider this: immune system helper cells, known as dendritic cells, present antigens from foreign invader cells to over a million of our T cells in a single day.