First published December 2004
Warning: This is a story about the mysterious disorder known as autism. About an epidemic that steals the minds of babies and young children. About noise in the brain, genes, environmental poisons and willful ignorance. About misconception and struggle. This is not a story about a cure. Or a surefire treatment. But it could be the first chapter in a much longer tale that ends with both.
Mysteries can do this to people, particularly mysterious diseases that strip away that warm blanket of unbridled promise that settles over the newly born. Autism, though, is a precise word for a very imprecise "spectrum disorder" that leaves children, usually between the ages of 18 and 36 months, with a range of mental, language, behavioral and social deficits. Still, the very breadth of the diagnosis and the varied collection of symptoms used to support it have led some to suspect that the presumed autism epidemic -- in California, the number of persons with diagnosed autism doubled to 20,000 in just four years -- is a statistical mirage.
It is undoubtedly true that parental fury over the alternate diagnosis -- namely, "mentally retarded" -- and the improved detection of autism's many shadings, along with the availability of treatment dollars in the nation's school districts have contributed to the surge. Yet they do not fully explain the dramatic rise in autism cases both nationally and worldwide. Countries as culturally diverse as Israel, Japan and Scotland, for example, all report increases on a par with, or worse than, the California figures. Nor do such semantic tussles change the cruel and alarming fact that an estimated 400,000 people in the US now lack the innate ability to communicate and learn normally or form social bonds. And with the incidence of autism estimated at anywhere from 4.5 to 20 of every 10,000 live births, more of the severely impaired are joining their ranks every day.
What is going on? And is there something about modern life that is fueling the autism fire? Across the country, scientists, including UCSF neuroscientist Mike Merzenich and neurogeneticist John Rubenstein, are looking for answers in the fetal development of the brain and the factors that may disrupt it. Clinical researchers, such as UCSF Autism Clinic director Bryna Siegel, are approaching the problem from the other direction by studying autistic children themselves and letting them provide practical cues as to how they might still learn and communicate -- cues that offer insight into their disordered brains.
It is painstaking, slow, theoretical, pragmatic and often discouraging work, but it is far from pointless. It seems clear, for example, that the roots of autism lie in malfunctioning genes. How else to explain why it runs in families? Statistics further cement the connection. When one identical twin is profoundly autistic, there is a more than 70 percent chance the second will be as well. And in those cases where the second twin is not similarly autistic, the child still displays inherited problems with language and social skills. Like other developmental disorders with a genetic twist, autism also strikes boys more often than girls: The ratio is now 4 to 1. These clues and the related warning signs, which include the onset of brain seizures in otherwise normal children, challenge scientists to devise a model for autism that explains the symptoms and grasps their underlying cause.
It is a risky and sometimes thankless task. Unified theories of any spectrum disorder, let alone something so baffling as autism, are easy targets for critics. Yet they must be proposed, if only to provide a structure against which new evidence can be judged. The task for non-scientists seeking to join them on this quest is equally hard, if for different reasons. To understand what may be going wrong requires that they first appreciate what normally goes right. And to that end, they must inevitably probe that wondrous stew of genes and proteins that turns a fertilized egg into a smiling baby of staggering evolutionary endowment.
The human brain arises in overlapping layers of nerve-rich tissue, beginning with the brainstem, home to the control regions of our most basic survival systems, such as breathing and heart rate. From about the 20th to 27th week of gestation, the developing fetus is able to distinguish different sound frequencies and respond to loud sounds pulsing through its mother's abdomen. Driving the process is the expression of genes, which in a complex dance with other genes and their workhorse proteins spell out the instructions for constructing everything from nerve fibers to cell surface receptors, down to the tiniest electrical detail. It is blindingly fast work. A baby's brain has an estimated 100 billion brain cells at birth and trillions upon trillions of connections by the age of three. Moreover, a single cell can connect with as many as 15,000 others. No wonder that the consequences of genetic errors can create a spectrum of problems.But what kind of errors could contribute to the particular range of communication and comprehension deficits seen in autistic children? And why do some of these children isolate themselves so profoundly from the external world, while others engage with it more readily?
UCSF neuroscientist Merzenich has spent his career pondering the complexities of brain function and studying the relationships among brain disorders, neural development and behavior. Merzenich is well-respected for his pioneering work in developing cochlear implants -- a medical device that has restored useful hearing to thousands of the previously deaf -- and in validating and expanding the concept that the brain rewires itself as it develops and learns, a concept known as brain plasticity. But it is the therapeutic implications he has drawn from his work that have made him a sometimes controversial figure.
Merzenich has always relished a good conceptual fight and his more than 50 patents and the two companies he has founded attest to his success at defying both the odds and naysayers. Autism may be his riskiest theoretical venture yet. Yet he has jumped into the ring wearing his characteristic Mona Lisa smile. "Talk to 10 different autism experts and you'll get 10 different stories. But what has been lacking in all of them is the tracking of the brain development process. It's clear to me that autism is the product of a developmental catastrophe."
Not surprisingly for someone who moves so fluidly from human behavior to neural circuits and back again, Merzenich has taken the language and learning deficits so common to many autistic children as his starting point. Building upon other work that pinpoints how and where these problems arise in the fetal brain, Merzenich -- in close collaboration with John Rubenstein -- has devised a model that both believe provides a plausible explanation for autism. "What it comes down to is noise in the brain," Merzenich asserts. Put another way, as the two wrote in their October 2003 article ("Model of Autism") published in Genes, Brain and Behavior, "It is highly likely that the brain systems that underlie language and social skills are at the core of autism."