According to the federal government, one in every 88 American children now has an autism spectrum disorder (ASD), and not all of the increase, most officials concede, can be traced to better diagnosis or awareness. The actual incidence of the disorder is increasing, they say, and the question is why.
Scientists have been on the hunt, and have rolled out a spate of new studies over the past several years. Is it genetic? Is it environmental? Is it perhaps both, an environmental factor that pulls the genetic trigger? What role do vaccines play?
The raft of recent studies link autism to any number of factors, from older mothers to older fathers to maternal obesity to pesticides to routine household cleaning chemicals to taking antidepressants during pregnancy.
Through the years, though, most of the research - and most of the money for research - has focused on trying to prove that autism is a genetic disorder, and, just this past week, three research papers published in the scientific journal Nature again pointed to the role played by genetics, this time by genetic mutations, also called de novo mutations. Essentially, a de novo mutation occurs spontaneously and is not an inherited defect.
What researchers with the Autism Sequencing Consortium found was a link between such mutations and the risk of autism. In Nature, they write that they studied 928 people, finding that "de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects."
In one paper, as The New York Times reported, reviewing 200 diagnoses of autism, as well as looking at parents and siblings without an autism diagnosis, the researchers impressively found two unrelated autistic children with de novo mutations in the same gene.
That gene-specific genetic glitch could be a coincidence, but it's also like lightning striking twice, and the papers have heartened genetic investigators. Still, while some hailed the studies as a breakthrough, confirming the considerable role genetics play in autism, others did not quite jump on the bandwagon.
For one thing, because a de novo mutation is not an inherited one, something else actually caused it. One of the new Nature papers implicated older male sperm as a potential culprit, but mutations could also be caused by a variety of factors, including such things as radiation, viruses and chemicals - in other words, an environmental cause.
Dr, Thomas Insel, the director of the National Institute for Mental Health, put it this way on his blog:
"It is important to understand that de novo mutations may represent environmental effects," Insel wrote. "In other words, environmental factors can cause changes in our DNA that can raise the risk for autism and other disorders."
Beyond the search for de novo mutations common to those with autism, other new research has recently widened the look into environmental factors as a cause. Indeed, and very significantly, a new study of twins last year points to nongenetic factors as well.
Published in the Archives of General Psychiatry, and entitled "Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism," the paper set out to "provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment."
The study was carried out by researchers at Stanford University and the University of California-San Francisco, and is the largest twin study of the genetic component of autism.
Other participants included Kaiser Permanente, UC Davis, the Autism Genetic Research Exchange and the California Department of Public Health. The research was funded by the National Institute of Mental Health, one of 27 institutes and centers of the National Institutes of Health, and by Autism Speaks.
The researchers looked at twins born between 1987 and 2004 in California, in which at least one of the siblings was diagnosed with autism.
The results? According to the paper, for male identical twins, ASDs were diagnosed in both twins in 77 percent of the cases; for females, the figure was 50 percent. For fraternal twins, the numbers were lower: 31 percent for males and 36 percent for females.
On the face of it, the finding of autism in one identical twin and not in another points to something other than genetics at work, since identical twins essentially share 100 of the same genes.
But the results of the researchers' mathematical modeling found something else even more surprising: The children's environment represented more than half of total susceptibility - 55 percent in the most severe form of autism and 58 percent in the broad spectrum of the disorder, the researchers stated - while genetics was involved in 37 percent and 38 percent of the risk, respectively.
"Autism had been thought to be the most heritable of all neurodevelopmental disorders, with a few small twin studies suggesting a 90 percent link," said UCSF geneticist Neil Risch, director of the UCSF Institute for Human Genetics and senior author of the paper. "It turns out the genetic component still plays an important role, but in our study, it was overshadowed by the environmental factors shared by twins."
So what are those environmental factors?
That, said Dr. Joachim Hallmayer, first author of the paper and an associate professor of psychiatry and behavioral sciences at Stanford University, was the "multimillion dollar question." He said the disorder's manifestation in very young children indicated a cause early in life and possibly during pregnancy.
And what about the role of vaccines?
While most researchers in the scientific establishment have long dismissed a link between vaccines and autism, the topic rages on within the autism community and among a minority of scientists. That's because many parents see the disorder manifest itself after various childhood vaccinations, when previously the child had appeared to be developing normally.
Most recently on this front, in 2011, Dr. Helen Ratajczak, herself a former pharmaceutical scientist, published a paper in the Journal of Immunotoxicology reviewing the collected body of science concerning autism and found that vaccines could not be ruled out as at least one cause or contributing factor.
"The incidence and prevalence data indicate the timing of introduction of vaccines and changes in the type and increasing number of vaccines given at one time implicate vaccines as a cause of autism," she concluded in her paper. "The current recommended immunization schedule for persons aged 0-6 years in the United States includes six vaccines at 2 months and nine vaccines at 12-15 months (Advisory Committee on Immunization Practices, 2010). This is an increase over recommendations 6 years before, with five vaccines at 2 months and 8 at 12-15 months (Advisory Committee on Immunization Practices, 2004)."
That's significant, she wrote, because the immune system is particularly sensitive at two months of age. Because the immune system of an infant is compromised at two months, "(a) challenge by so many vaccines while the immune system is compromised might contribute to an onset of autism."
Vaccine antigens might be complicit as well, Ratajczak wrote.
"There are many controversies about vaccines and autism, especially since many parents cite normal development of their children until they receive vaccines at about the age of 18 months (Lewine et al., 1999)," she wrote. "The vaccine organism itself could be a culprit."
For example, she wrote, some speculate that a cause of autism is the pertussis toxin in the DPT vaccine, while others have pointed to the live measles virus. Still others point to mercury that remains in some vaccines - "in trace amounts," according to the federal government - and in multi-dose formulations if popular flu shots.
Others point to other chemical additives in vaccines, such as aluminum adjuvants. Aluminum has been linked to neurological disease.
Chasing the cost
Meanwhile, based on prevalency numbers, scientists are chasing autism's cause or causes with scarce dollars compared to research in other areas. For example, of the 2011 National Institutes of Health's budget of $30.5 billion, only $169 million went directly to autism research.
That comes to about 25 percent of what the NIH will spend on breast cancer research and $50 million less than what it will spend on asthma, according to Autism Speaks, an advocacy group.
Such advocacy groups themselves have contributed more than $300 million in additional funding, about a third of which goes to the search for the causes of autism.
More children will be diagnosed with autism this year than with AIDS, diabetes and cancer combined, and ASD costs the nation an estimated $126 billion per year.
Autism receives less than 5 percent of the research funding of many less prevalent childhood diseases, Autism Speaks points out.
Richard Moore may be reached at firstname.lastname@example.org