Thursday, April 5, 2012

Genetic Reductionism in Autism: Deliberate Marginalization of Environmental Contributions?

Majia here: I am getting tired of this narrative that autism is directly caused by genes.

Yes, genes play a role in autism. 

However, the evidence strongly suggests that environmental factors are what impacts the genetic processes that lead to autistic symptoms.

I'll explain below, but the reason I'm writing this once again (I've posted on this subject many times) is because another headline is circulating that frames autism as a genetic disorder. The framing implies that autism is hereditary and that environment plays little-to-no-role.

Here is the headline and the first few sentences. Notice how the role of genes is emphasized: 

Scientists Link Gene Mutation to Autism Risk. The New York Times. By Benedict Carey.

[excerpted] "Teams of scientists working independently have for the first time identified several gene mutations that they agree sharply increase the chances that a child will develop autism. They have found further evidence that the risk increases with the age of the parents, particularly in fathers over age 35.

The gene mutations are extremely rare and together account for a tiny fraction of autism cases — in these studies, only a handful of children. Experts said the new research gave scientists something they had not had: a clear strategy for building some understanding of the disease’s biological basis.

Scientists have been debating the relative influence of inherited risk and environmental factors in autism for decades, and few today doubt that there is a strong genetic component....

Majia here: Notice in the text I've quoted above that genetics is separated from environment as if genes and environment were two distinct forces. The text implies that genes have emerged in the research as triumphant over environment. 

This is a fallacious framing and Benedict Carey who wrote the article should know better as he has been writing science for the NYT for a very long time. 

The framing of genes as a force separate, distinct, and ascendant over environment is fallacious.

The research being cited in the article has found correlations between de-novo mutations in a particular gene and autism.

Here is the quote from the NYT article above that explains these findings:

"In all three studies, the researchers focused on rare genetic glitches called de novo mutations.

De novo mutations are not inherited but occur spontaneously near or during conception. Most people have at least one, and the majority of them are harmless...."
Majia Here: De novo mutations are NOT inherited, as the article acknowledges. 

De Novo mutations appear random. 

People with autism have been found to have more de novo mutations than the general population, but usually do not share the same ones (see Geschwind, 2008).

One of the studies reported in the NYT article (by Matthew State) found 2 unrelated children with de novo mutations in the same gene out of 200 people. I'm not even sure if that is a statistically significant finding.
What I think is more important is that the research has found that the father's age is correlated with the mere presence of de novo mutations in kids with autism.

The relationship between the father's age and de novo mutations seems to me a very clear indicator of environmental contributions.

As we age our bodies' abilities to repair genetic damage wanes. Damage to germ cells from radiation or chemicals could potentially result in de-novo mutations in offspring. 

Hence, the CAUSE of the GENETIC MUTATIONS could very well be ENVIRONMENTAL.

For example, look at this study.

Ionizing radiation-induced mutant frequencies increase transiently in male germ cells of older mice  Guogang Xua, C. Alex McMahanb, Kim Hildretha, Rebecca A. Garciaa, Damon C. Herberta, Christi A. Walter Mutation Research/Genetic Toxicology and Environmental Mutagenesis Available online 31 January 2012


Spontaneous mutant frequency in the male germline increases with age, thereby increasing the risk of siring offspring with genetic disorders. In the present study we investigated the effect of age on ionizing radiation-induced male germline mutagenesis. lacI transgenic mice were treated with ionizing radiation at 4-, 15- and 26-month-old, and mutant frequencies were determined for pachytene spermatocytes and round spermatids at 15 days or 49 days after ionizing radiation treatment.

Cells collected 15 days after treatment were derivatives of irradiated differentiating spermatogenic cells while cells collected 49 days later were derivatives of spermatogonial stem cells. The results showed that (1) spontaneous mutant frequency increased in spermatogenic cells recovered from nonirradiated old mice (26-months-old), particularly in the round spermatids; (2) mutant frequencies were significantly increased in round spermatids obtained from middle-aged mice (15-months-old) and old age mice (26-months-old) at 15 and 49 days after irradiation compared to the sham-treated old mice; and (3) pachytene spermatocytes obtained from 15- or 26-month-old mice displayed a significantly increased mutant frequency at 15 days post irradiation.

This study indicates that age modulates the mutagenic response to ionizing radiation in the male germline.

[excerpt from article] "Advanced paternal age (about 40 years or older at the time of conception) is associated with an increased incidence of a wide range of genetic and epigenetic diseases in offspring [2]. For example de novo mutations (C to G in fibroblast growth factor receptor 2 (FGFR2) gene) in 57 Apert cases were all of paternal origin…In addition to several diseases with clear Mendelian inheritance, advanced paternal age is also linked to an increased risk for diabetes with a genetic component such as childhood cancers [5-7], diabetes mellitus type [8], multiple sclerosis [9], autism [10] and congenital malformations [11], and others. The association between paternal age and increased risk for diseases in offspring may be at least partially ascribed to mutagenesis in male gametes [12-16]."

MAJIA HERE: This study suggests that mutagenesis in male gametes CAN BE CAUSED BY IONIZING RADIATION.

Hence, although autism involves genes, it is the role of environment in causing genetic errors that should be studied.

below find an excerpt from a chapter I've written on autism, genetic reductionism, and the environment:

New DNA imaging technologies have revealed de novo (not seen in parents) structural variations, such as microdeletions and duplications in DNA segments linked to autism, particularly on chromosome 16. However, most of the copy number variations detected in microarray research appear to be “rare, essentially private, mutations in simplex (one affected child) autism families” (Geschwind, 2008, p. 394). Viruses, environmental contaminants, and ionizing radiation all emerge as potential exogenous factors figuring into susceptibilities for mutations.
Despite the ambiguity about the role of genes in causing autism, the public has been educated to regard autism as a hereditary disorder. Popular websites such as WebMd typically prioritize genetics in their introductory accounts of autism, as illustrated here at WebMd’s “Autism Symptoms, Causes, Treatments, and more”: “The exact cause of autism is not known, but research has pointed to several possible factors, including genetics (heredity), certain types of infections, and problems occurring at birth.” 

Likewise, Parenting Magazine notes in their section on “New Autism Facts and Figures” that “We're getting closer to understanding the possible causes. Groundbreaking research last year pinpointed what scientists are calling autism ‘susceptibility’ genes, which regulate how the brain develops and how connections between cells are made. . . .” Although, the article does acknowledge that individuals who have the susceptibility genes do not necessarily have autism.
This framing of autism as a genetic disorder has dominated public research priorities, expert discourse about autism in the media, and commercial product developments pertaining to autism. For instance, the same WebMd article explains under the heading of “What Autism Research Is Being Done?” that “The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, is studying brain abnormalities that may cause autism and is looking for genes that may increase the risk of autism” (ADD REFERENCE). 

Funding agencies such as the NIH have prioritized the research goal of finding autism susceptibility genes. For instance, in 2004 the NIH issued a Request for Proposal for Identifying Autism Susceptibility Genes” (RFA-MH-05-007) that would make $4,295,000 available in FY 2005.
Furthermore, in 2007, three of the six Autism Centers of Excellence  research awards focused on brain imaging studies, two focused on genetic based causes (one of which also used neuroscience), and one focused on behavioral interventions.  In 2008, the ACE program Center award was for a study seeking to identify rare genetic variations believed to play a role in autism.  In 2008, ACE program Network award recipients included three grants studying: genetics; pharmaceutical treatment with Buspar; and, atypically, an environmental risk study. 

A study of NIH funding priorities for autism from 1980 to 2007 by Blaxill, Bernard and Wrangham (n.d.) found that genetic and imaging grants were strongly favored. Treatment using pharmaceuticals and screening were also prioritized, while environment-only studies were strongly de-emphasized when funding was allocated. In 2009, Johns Hopkins University announced receipt of an ACE award to study the intersection of genetics and autism. 

This list of funded research priorities illustrates the strong emphasis placed on genetic research and neuroscience and, to a lesser extent, research on biomarkers, screening, and drug treatment. It also illustrates the de-emphasis on environmental factors, which, when investigated at all, are cast in relation to genetic susceptibilities. Funding prioritizes research that simply aims to identify genes linked to the disorder and/or brain anomalies that deviate from the neural profiles of “normal” populations. 

Research assessing the appropriateness and effectiveness of actual therapeutic practices is almost non-existent. Federal and private funding for autism privileges research that studies autism as a genetic and brain based disorder. In contrast to research funding, public funding for services for people with autism does not exist to any significant degree at the national level in the US....

The Children’s Environmental Health Center at Mount Sinai reports that only 20 percent of the more than 80,000 new chemicals produced since World War II have been tested for toxicity in children (Kristof, 2009). 

In August of 2007 the U.S. Government Accounting Office (GAO) published a report comparing the lax U.S. regulatory framework for chemicals with a recently enacted European framework, REACH. The GAO report (GAO-07-825) explains that under the current regulatory system in the U.S., companies do not have to develop information on the health or environmental impact of chemicals unless specifically required by EPA ruling. 

Consequently, the EPA relies on voluntary programs for gathering information from chemical companies in order to evaluate and regulate new chemicals under the provisions of 1976 Toxic Substances Control Act (TSCA) legislation.  The GAO report’s recommendation that the burden of risk be shifted to the chemical companies was not adopted by the George W. Bush Administration, even after former President Bush’s cancer panel found a strong link between environmental toxins and cancer (see Layton, 2010b, The President’s Cancer Panel, 2010). 

In 2010 a new regulation to overhaul the now outdated 1976 TSCA were introduced, but so far nothing has been passed (see Layton, 2010a;  “Momentum,” 2010). 
Chemicals are not the only environmental factor that may be implicated in autism. Ionizing radiation has received almost no attention in the environmental research on autism, yet in my opinion there exists considerable likelihood that it may play a role in the disorder. 

Research has demonstrated that even low-doses of ionizing radiation can cause childhood leukemia (Little, Wakeford, & Kendall, 2009). Environmental researchers have pointed out that radiation risk-exposure standards are based on adult standards and children are a sensitive subpopulation whose biological vulnerabilities have not been properly assessed for risk-management standards (see Fucic, Brunborg, Lassan, Jezek et al, 2008; Preston, 2004). 

Furthermore, natural killer (NK) cells that have been implicated as being deficient in children with autism (Enstrom, 2008) are particularly susceptible to damage from ionizing radiation (Vokurková, et al., 2010). The nuclear power/weapons industry has been very successful in deflecting attention away from radiation as an environmental risk.

Conclusion: Yes genes play a role, but that role is mediated by environment.

Balxill, M., Bernard, S., & Wrangham, T. (n.d.). NIH & Autism: A case study in barriers to progress in environmental medicine. Safeminds. Available:

Enstrom, A. M., Lit, L., Oncore, C.E., Gregg, J. P., Hansen, R. L., Pessah, I. N., Hertz-Picciotto, I., Van de Water, J. A., Sharp, F. R., Ashwood, P. (2008). Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain, Behavior, Immunology, 23(1), 124-133.
Fucic, A., Brunborg, G., Lasan, R., Jezek, D., Knudsen, L.E., Merlo, D.F. (2008). Genomic damage in children accidently exposed to ionizing radiation: A review of the literature. Mutation Research/Reviews in Mutation Research, 658(1/2), p.111-123.
Geschwind, D.H. (2008). Autism: Many genes, common pathways? Cell, 135(3), 391-395.

Landrigan, P. (2010).What causes autism? Exploring the environmental contribution. Current Opinion in Pediatrics, 22, 219-225.
Layton, L. (2010a, April 15). Lautenberg bill seeks to overhaul U.S. chemical laws. The Washington Post, p. A6.

Momentum Builds in Congress to Overhaul U.S. Chemicals Policy. (2010, July 23). Earthjustice. Available:
President’s Cancer Panel. 2008-2009 Annual Report. Reducing Environmental Cancer Risk: What We Can Do Now. Available:
Preston, J. R. (2004). Children as a sensitive subpopulation for the risk assessment process. Toxicology and Applied Pharmacology, 199(2), 132-141.  

Vokurková, D., Vávrová, R., Sinkora, A., Stoklasová A.,  Bláha, V., Rezá, M. (2010). Radiosensitivity of CD3_CD8þCD56þ NK cells. Radiation Measurements, 45, 1020-1023.


1 comment:

  1. Clarification: once acquired, de novo mutations in germline cells CAN be transmitted to the next generation.

    That said, the focus of research is on novel, or newly acquired, de novo mutations


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