Herbert believes that the clues linking the obvious behavioral symptoms to more basic, but less obvious, biological dysfunction were missed early on. “What I believe is happening is that genes and environment interact, either in a fetus or young child, changing cellular function all over the body, which then affects tissue and metabolism in many vulnerable organs. And it’s the interaction of this collection of troubles that leads to altered sensory processing and impaired coordination in the brain. A brain with these kinds of problems produces the abnormal behaviors that we call autism.”
Yellow regions (top) show the enlarged
white matter found in autism patients. Red
regions (below) show the gray matter
which is relatively smaller in autism
patients.
(Courtesy of the Center for Morphometric
Analysis, MGH-Harvard)
Herbert’s full-body perspective helps make sense of the confusion surrounding the diagnosis of autism and helps justify the increasingly common use of the plural “autisms” to describe the wide variations in this disorder. As Newschaffer points out, “Children with Asperger’s syndrome certainly share a lot of the behaviors of those with more severe autism. But is it the same disease, and is it caused by the same thing? A number of significant features of autism are not part of the diagnostic schema right now, but eventually, those features may end up distinguishing one causal pathway from another. How is a child sleeping? Does he or she have gastrointestinal symptoms? By looking at those things we may see risk-factor associations pop out that we’ve never seen before.”
Herbert likens autism to a hologram: “Everything that fascinates me is in it. It’s got epidemiology, toxicology, philosophy of science, biochemistry, genetics, systems theory, the collapse of the medical system, and the failure of managed care. Each child that walks through my door is a challenge to everything I ever knew, and each child forces me to think outside the box and between categories.”
Each child’s path to autism may be distinct, she says, but they may share common inflammatory abnormalities. She has shown through morphometric brain imaging that white matter—which carries impulses between neurons—is larger in children with autism.
“It was the most absolutely outstanding piece of information in all the brain data I looked at,” Herbert recalls of the years 2001 and 2002, when she was analyzing this brain imaging data. “People were saying, don’t look at the white matter, look at the cerebral cortex, but I knew we had an important finding.”
Could white matter become chronically inflamed? It may well be, according to new research from Carlos Pardo, a neurologist at Johns Hopkins. In a 2005 study in the Annals of Neurology, he found inflammation in immune-responsive brain cells of autistic patients. “Patients with autism report lots of immunological problems. We looked for the fingerprints of those problems in the brain,” says Pardo. “We had brain tissue from autistic individuals as young as 5 and as old as 45 and we found neuroglial inflammation in all of them. Neuroglia are a group of brain cells that are important in the brain’s immune response. This inflammatory reaction appears to happen both early and late in the course of the disorder. If it happens early, it could dramatically influence brain development. We’re very excited about this research because one potential treatment approach, then, is to downregulate the brain’s immune response.” To study that approach, Pardo is collaborating on a pilot study funded by the NIH to test minocycline, an anti-inflammatory antibiotic drug, on autistic children. “Minocycline is a very selective downregulator of microglial inflammation,” he says. “Neurologists already use it in multiple sclerosis and Parkinson’s.”
“What we’ve got here is a far more comprehensive set of characteristics for autism,” says Herbert, “one that can include behavior, cognition, sensorimotor, gut, immune, brain, and endocrine abnormalities. These are ongoing problems, and they’re not confined just to the brain. I can’t think of it as a coincidence anymore that so many autistic kids have a history of food and airborne allergies, or 20 or 30 ear infections, or eczema, or chronic diarrhea.”
All this marks a Copernican-scale shift in our approach to the disorder. I myself was irresistibly drawn to the subject when viewing an online video of a heavily affected 11-year-old who, after a series of chelation treatments to remove mercury, announced to his mother, “Mom, I’m back from the living dead.” The statement was heartbreaking in its simple eloquence. Mercury chelation, in this particular child’s case, was a near panacea.
Lisa Beck, of Oviedo, Florida, tells a similar story. Her son Joshua was diagnosed with autism in 2004 at about age 2. After 18 intensive months of treatment that involved chelation—a treatment that draws heavy metals out of the body—and dietary changes, among other therapies, Josh appears neurotypical. “We took him to Dr. Leslie Gavin, a specialist at Nemours Children’s Clinic, who administers the ADOS test, a diagnostic test to see where on the spectrum a child falls,” she says. “After the two-hour evaluation, Gavin said he did not meet the criteria for autism. In her words, he was ‘responsive, curious, and active, able to engage in the test without a problem, able to express himself clearly.’ ”
But, fascinating anecdotes aside, does hard evidence exist of specific vulnerability genes or how they might impair the immune system, brain, and gut—and most important, do we have any rational, reliable approaches to help repair the damage?
The answer is a provisional yes.
