Teresa Binstock exposed the mindset that directed funding almost exclusively towards genetic based autism research over a decade ago. Years later, and with little to show for the nearly cult like belief that autism is, that autism must be, that autism just has to be, 100% genetic, and public autism research funding dollars still flow almost exclusively toward genetic based autism research. This one way flow of research funding has prevented us from greater understanding of the environmental factors that might be causing or triggering autism in children's prenatal and neonatal development. This week, in the Children's Health Subcommittee of the US Senate Senate Committee of Environment and Public Works, the "autism is 100% genetic myth" was busted. Despite few research dollars flowing toward environmentally based autism research it is environmental factors that are beginning to provide some understanding of autism and other neurodevelopmental disorders.
| 1. Paul Anastas Ph.D. |
Assistant Administrator for Research and Development and Science Advisor U.S. Environmental Protection Agency (EPA)
Dr. Anastas gave a very careful and conservative review of existing environmental research with implications for autism and other developmental disorders. By way of background he noted:
"children are especially susceptible to the effects of chemicals in the environment because they eat, drink and breathe in more for their body weight than adults. They absorb a greater proportion of many chemicals in the environment than adults do, and due to hand to mouth behaviors, young children tend to have higher exposures to contaminants in dust and soil, such as pollutants deposited from the surrounding air, dust from lead paint, tobacco smoke, cleaning products, pesticides and other chemicals.3, 4 Because of its extraordinary complexity, prenatal and early postnatal brain and nervous system development can be disrupted by environmental exposures at much lower levels than would affect adults.5,6,7,8,9 We are learning that there are critical windows of susceptibility both prenatally and in early childhood, during which the effects of exposures to environmental contaminants, depending on dose and timing, can be significantly more severe and can lead to permanent and irreversible disability.10,11,12 For these and many other reasons, EPA is especially concerned about potential effects of environmental chemicals on children’s health and neurodevelopment.
It has been suggested that improvements in diagnosis may be contributing to the perceived increase in ASDs. However, one recent publication from researchers supported by EPA and the National Institute of Environmental Health Sciences (NIEHS) evaluated the rise in autism incidence in California from 1990 through 2006. They found that even when factors such as earlier diagnosis, changes in diagnostic criteria and inclusion of milder cases were taken into account, these did not fully explain the observed increase, and as a result the extent to which the continued rise represents a true increase in the occurrence of autism remains unclear.13 Additionally, through a recent evaluation of autistic disorder (AD) data from long-term (~ 10 years) studies , ORD scientists found significant and surprisingly uniform timing of increases in AD cumulative incidence (1988-1989) in Danish, California and worldwide data sets.14 It is not clear if the observed increase in AD is real, and if so, for what reason; or whether the apparent increase is due to improved diagnosis, increased observations, or other factors. However, these researchers concluded that it seems prudent to assume that at least some portion of the observed increase is real and results from environmental factors interacting with susceptible populations.14 Such exposures may be preventable; identification of candidate environmental factors should be a research priority.
The challenge is to determine what specific environmental factors may contribute to the onset or severity of autism and other neurodevelopmental disorders, so that exposure to these can be prevented."
2. Linda Birnbaum, Ph.D., D.A.B.T., A.T.S. Director, National Institute of Environmental and Health Sciences and National Toxicology Program National Institutes of Health, United States Department of Health and Human Services
Dr. Birnbaum commented on the emerging emphasis on genetic and environmental interaction in understanding neurodevelopmental disorders:
"Scientists have made tremendous progress in understanding how the brain and nervous system grow and function. Research supported by NEIHS has clearly shown that it is not just genetics, but the complicated interplay of both genes and environment that determines the risk of many neurodevelopmental disorders. We now have new information on the role that early environmental exposures may play in the development of a broad spectrum of childhood and adult disorders, including autism, attention deficit hyperactivity disorder (ADHD), and learning disorders."
...
Development of the nervous system begins in the womb and extends through childhood. During these periods of rapid development, the brain is vulnerable to some environmental exposures that may have the potential to disrupt the chemical signals that organize development. Even small changes in the timing of critical development events can potentially have major consequences for brain structure and function. Thus even brief exposures at these vulnerable stages can have lasting effects on adult brain function. We refer to "windows of susceptibility: to mean the life stage at which the brain is exposed, during which different agents can effect the brain in specific and deleterious ways. For example, the dose of lead that is neurotoxic to an infant is much less than the dose that would be neurotoxic for an adult, so infancy in this case is a "window of susceptibility",
Director Birnbaum commented specifically on the effect of environmental exposures on children's intelligence. The "vast majority", to use the expression of CDC autism expert Dr. Yeargin-Allsopp, of children with Autistic Disorder (which does not include Aspergers) also have intellectual disabilities. I have photocopied Director Birnbaum's summary of the research on this important subject:
Dr. Pessah began his testimony before the subcommittee with a direct challenge to the view that diagnostic change is a full explanation for autism increases and that autism is 100% genetic:
"Although autism risk has strong heritability, no single locus alone appears to be sufficient to account for the full clinical phenotype. Results from many genomewide autism screens indicate that potential susceptibility genes are spread across the entire genome. Recently several very rare genetic mutations, single nucleotide polymorphisms (SNPs), de novo copy number variations, and epigenetic factors that influence DNA methylation were shown to contribute complexity in the transmission of autism risk. Yet genetics alone cannot account for the majority of autism cases currently being diagnosed. There is lack of full concordance between monozygotic twins, with some estimate ranging as low as 60%, and the prevalence of ASD among siblings has been reported as high as 14%. Interactions among multiple genes are likely to contribute to various types of autism, and heritable epigenetic factors and/or non-heritable environmental exposures are likely to significantly contribute to susceptibility and variable expression of autism and autism-related traits. It is therefore likely that constellations of epigenetic and environmental factors are contributing to the increasing prevalence of ASD, a rise that cannot be fully accounted for by changes in diagnostic criteria.
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There is a critical need to identify environmental factors, including exposure to xenobiotic chemicals and changes in diet that contribute to autism risk and severity. The vast majority of public and private resources has, and continues, to support work on identifying genetic impairments associated with autism risk. From these studies we have learned that genetics alone cannot predict the majority of autism cases, the patterns of impairments, severity, nor can they predict success for current treatment modalities. Moreover, we have learned that many of the molecular and cellular systems that are associated with autism are the very same ones that are the target of environmental chemicals currently of concern to human health because of their widespread use.
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We know that autism prevalence continues to increase dramatically clearly implicating environmental factors in autism risk. We must identify which environmental exposures and combination of exposures are contributing to increased overall risk in the population and identify the most susceptible groups. Only by bringing together the concerted effort of multidisciplinary teams of scientists can we identify which of the >80,000 commercially important chemicals currently in production promote developmental neurotoxicity consistent with the immunological and neurological impairments identified in individuals with idiopathic autism. It is clear that there is a critical need to identify which chemicals in the environment that influence the same biological pathways known to be affected in autism. Limiting exposure to these chemicals is the only way to mitigate or prevent autism in susceptible individuals. (Bold emphasis added - HLD)
....
There is a critical need to identify environmental factors, including exposure to xenobiotic chemicals and changes in diet that contribute to autism risk and severity. The vast majority of public and private resources has, and continues, to support work on identifying genetic impairments associated with autism risk. From these studies we have learned that genetics alone cannot predict the majority of autism cases, the patterns of impairments, severity, nor can they predict success for current treatment modalities. Moreover, we have learned that many of the molecular and cellular systems that are associated with autism are the very same ones that are the target of environmental chemicals currently of concern to human health because of their widespread use.
..
We know that autism prevalence continues to increase dramatically clearly implicating environmental factors in autism risk. We must identify which environmental exposures and combination of exposures are contributing to increased overall risk in the population and identify the most susceptible groups. Only by bringing together the concerted effort of multidisciplinary teams of scientists can we identify which of the >80,000 commercially important chemicals currently in production promote developmental neurotoxicity consistent with the immunological and neurological impairments identified in individuals with idiopathic autism. It is clear that there is a critical need to identify which chemicals in the environment that influence the same biological pathways known to be affected in autism. Limiting exposure to these chemicals is the only way to mitigate or prevent autism in susceptible individuals. (Bold emphasis added - HLD)
4. Bruce P. Lanphear MD, MPH Senior Scientist, Child & Family Research Institute, Professor, Simon Fraser University, Vancouver, BC, Adjunct Professor, Cincinnati Children's Hospital Medical Center
Dr. Lanphear 's prepared statement was relatively brief and to the point; and the body of the statement is reproduced below with my empahsis in bold:
Children’s environmental health -- the study and prevention of disease and disabilities in children from exposures to social, physical, biologic, and chemical agents -- has emerged as a new field of research, policy, and clinical practice (Landrigan et al. 1998). The growth of this field has been fueled by the emergence of new morbidities in children, research showing that the fetus and child are particularly vulnerable to environmental influences, and mounting evidence implicating environmental exposures as major risk factors for prevalent diseases and disabilities in children (Lanphear, 2005).
One in six American children have a developmental problem, from a subtle learning disability to overt behavioral disorders, such as attention deficit hyperactivity disorder (ADHD) or autism (Boyle et al. 1994; Hertz-Picciotto, 2009). These conditions can severely impair a child’s ability to succeed in school, elevate their risk for violent and criminal behaviors, and dramatically diminish their ability to contribute to society. The findings from some of the most thoroughly studied and widely dispersed environmental toxicants indicate that exposure to exceedingly low levels are risk factors for the “new morbidities” of childhood -- intellectual impairments, behavioral problems, asthma and preterm birth (Lanphear, 2005). Indeed, there is often no apparent threshold and, in some cases the effects appear to be greater at the lowest levels of exposure (England et al. 2001; Canfield et al. 2003; Lanphear et al. 2005; Yolton et al. 2005).
Exposures to established environmental toxicants -- such as lead, tobacco, PCBs and mercury -- have consistently been linked with higher rates of intellectual impairment or behavioral problems, such as conduct disorder and ADHD (Needleman et al. 1990; Schantz et al. 2003; Kahn et al. 2003; Wakschlag et al. 2002; Stewart et al. 2003; Needleman et al. 1979; Lanphear et al. 2005; Yolton et al. 2005). There is emerging evidence that a whole host of new environmental chemicals – such as Bisphenol A, PBDEs, pesticides, phthalates, and airborne pollutants – are associated with intellectual deficits or behavioral problems in children, but the evidence is not as conclusive (Rauh, 2006; Engel, 2010; Eskenazi, 2007; Braun, 2009; Perera 2009; Herbstman, 2010). Much of this research was done by the NIEHS/US EPA Children’s Environmental Health Research Centers working collaboratively with the Centers for Disease Control and Prevention.
Children’s developing brains are more vulnerable to certain toxicants and pollutants than adults. The central nervous systems of the fetus and young child, which are undergoing rapid changes, are particularly vulnerable to some toxicants. The fetus is a recipient of toxicants through placental transfer (Perera et al. 2003; Whyatt and Perera 1995; Bearer 2003). In some cases, such as mercury, the fetus is exposed to a larger dose than the mother (Ramirez et al. 2000). In other cases, such as organophosphate pesticides, the fetus may lack critical enzymes to metabolize environmental toxicants (Chen et al. 2003). Toddlers are often at greater risk for exposure to many environmental toxicants because they have a high degree of hand-to-mouth activity and they absorb some toxicants more efficiently (Bearer 1995).
Biomarkers are revolutionizing our ability to study the impact of environmental chemicals on neurodevelopmental disabilities (Perera, 1997; Lanphear and Bearer 2005; CDC 2003; Sexton et al. 2004). Historically, scientists and clinicians relied on indirect markers -- housing condition, poverty, questionnaires, and community-level monitoring of water and air -- to quantify the effect of environmental influences on children’s health (Sexton et al. 2004). Biomarkers are making it possible to directly measure the internal dose for many environmental chemicals and test causal associations of environmental exposures with disease and disability in children.
I wanted to share some of the results of the Cincinnati Children’s Environmental Health Center to highlight the impact of low-level toxicity on children. In a 2003 study, published in the New England Journal of Medicine, we estimated that an increase in blood levels from <1 μg/dL to 10 μg/dL was associated with a 7 IQ point decrease (Canfield, 2003). Because of the policy implications, we convened an international group of experts to conduct a pooled analysis of seven cohort studies. We estimated that an increase in blood levels from <1 μg/dL to 10 μg/dL was associated with a 6 IQ point decrement (Lanphear, 2005). These studies have been confirmed by over ten studies conducted around the world.
We also confirmed earlier reports implicating childhood lead exposure in the epigenesis of psychopathology in children. We estimated that one in five cases of ADHD in US children were due to childhood lead exposure (Froehlich, 2009). We also found joint effects of prenatal tobacco exposure and childhood lead exposure. Although each toxicant was associated with a 2.5-fold elevated risk for ADHD, children with higher exposures to both toxicants had a 8-fold elevated risk for ADHD (Froehlich, 2009).
Finally, we confirmed that childhood lead exposure is a risk factor for criminal arrests in young adults. We found that lead exposure is associated with conduct disorder, criminal arrest and impaired brain development using magnetic brain imaging (Braun, 2008; Cecil 2008; Wright, 2008; Brubaker 2009). These and other studies suggest that much of the criminal and violent behaviors in the US can be attributed to lead toxicity (Nevin, 2000; Reyes, 2007). Gould used these studies to conduct a cost-benefit analysis of lead toxicity. She estimated that for every dollar spent to reduce lead exposure, society would benefit by $17 to $220, a net annual benefit of $30 billion to $44 billion (Gould, 2009).
Over the past century, increasing evidence has emerged linking chronic, low-level exposure to environmental influences and industrial pollutants with many of the most prevalent and disabling learning and behavioral problems in children. But questions remain. It is critical, for example, to examine the interactions of multiple environmental toxins or pollutants and to identify how genetic susceptibility or other markers of susceptibility elevate the risk for disease or disability. It is critical to discern whether the new chemicals are risk factors for autism and other emerging behavioral problems in children. Funding that is directed to children’s environmental health research – the Children’s Environmental Health Centers, the National Children’s Study and other research awards -- offers us the opportunity to resolve many of the unanswered questions and prevent some of the most serious problems that impact children’s learning abilities and behavioral problems, but much more needs to be done.
A parent Mary Moen also testified before the committee giving evidence familiar to many of us of the challenges of raising a child with an autism disorder and an 48 year old family member, suspected of being autistic, who has lived dependent on the care of her aging parents.
The evidence of the experts who testified before the Children's Health Subcommittee of the US Senate Committee on Environment and Public Works have clearly busted the myth that autism, and other neurodevelopmental disorders are 100% genetic. They have presented studies of the known toxic substances including mercury, lead and various pollutants which we inhale, consume or are exposed to and the much harsher impact these substances have on prenatal and neonatal neurological development.
It will take time for this information to permeate the public consciousness. The "it's gotta be genetic" mindset is too deeply entrenched in the culture of public health authorities in Canada and the US to change quickly. There are vested corporate interests for whom a 100% genetic theory of autism absolves them of any possible responsibility for harm caused by their products. There are traditional media sources hungry for corporate advertising dollars who will read the latest script offered up by the pharmaceutical marketing/research departments who will dutifully report that autism is 100% genetic and damn those crazy parents of autistic children who just can't accept that "fact" and take responsibility for what our genes have done to our children. The "it's gotta be genetic" mindset is also helped by the Neurodiversity ideologues for whom autism is just a natural variation, not a disorder to begin with, and who abhor any discussion of environmental causes of autism because, heaven forbid, the existence of known environmental triggers of autism might confirm that their DSM autism diagnosis is what it claims to be when it was obtained by visits to a qualified physician ... a neurologically based mental disorder.
This is one case though where the truth, as it did with the tobacco and lung cancer issues of decades past, will out. The overwhelming commitment of research dollars to genetic based autism research has yielded very, very few results and has failed to identify common genetic bases for autism. That failure, and the environmental research cited before the US Senate, which resulted from relatively limited research funding, both point to environmental factors as triggers and causes of autism disorders in interaction with genetic factors.
The truth will out but it is long past time to even out the funding , as Dr. Irva Hertz-Picciotto has called for, and direct some of the genetic based autism research dollars toward more environmentally focused autism research. The autism is 100% genetic myth is dead. It is time to fully embrace the environmental genetic interaction model of autism and find out how to help our autistic children and children not yet born.
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