How much of a condition can be explained by environmental influences and how much can be explained by genetic factors? This has been an outdated polemic within the life sciences that is now making rounds in autism. The new take on the old debate is a third alternative that combines both Nature and Nurture; that is, one that takes into consideration the fact that both genes and environment influence each other. This concept belongs to the new field of “epigenetics”.
There are some 5,000 risk genes for autism out of a total of some 22,000 expressed by human DNA. This means that one out of approximately every 4 genes within our chromosomes, if changed or altered, may provide some type of susceptibility to autism. Our state of ignorance is so large that for some of these genes we do not even know if they are expressed in the brain vs. other parts of the body.Establishing mechanism(s) by which both genes and environment affect the brain is therefore difficult. In a previous article our group has discussed a commonality among defined autism risk genes, which is their ability to mutate. Autism risk genes, in general, have large elements within them (called transposable elements or “jumping genes”) that make them susceptible to mutations (Williams et al. Translational Neuroscience 4(2):172-202, 2013). Our work indicates that when focusing on autism risk genes we should look not only at their role in any particular biochemical pathway but also at their composition and 3D structure.
Figure above. Although it makes no sense to study genes in isolation from the environment funding provisions by the NIH are extremely biased in autism. This is more striking when considering the fact that autism is readily acknowledged to be a multifactorial condition. Not surprisingly, after spending all of the money on purely genetics research, results have been disappointing. (Double click on the image to make the same larger).
Environmental research has not been less confusing than genetic studies. The Childhood Autism Risks for Genetics and the Environment (CHARGE) study from the MIND institute was launched in 2003. The problem with the study and others similar is not in their ability to flag down suspects, but rather, they have flagged down way too many; be it pesticides, fever during pregnancy, prenatal vitamins like folic acid, living close to main roads (freeways), etc. At this rate it seems possible that the number of environmental triggers will likely surpass the total number of gene risk factors! These discoveries are made without taking into account the genetic make-up of participants. Worse still, these discoveries are made without adequate explanations to the known pathology of autism. Do they in any way explain changes in brain volume size during postnatal growth? Do they disturb neuronal migration to the cortex? Do they reduce long connections from disparate areas of the brain? If they do not explain anything we know about autism, are they capable of explaining things we did not know about the condition (predictive ability)? It is easy to postulate results from a massive database when you do not feel compelled to explain how your own findings relate to previous ones in the literature.
There are many limitations to environmental studies. I think the most important is the inability to use quantitative tests that differentiate environments. You can live closer to a freeway but as a result of having a better job that takes you closer to the metropolitan commerce hub. Living closer to a freeway may also be related to your accessibility to bookstores or fast food places (junk food), how many books you have at home, or even the type of vocabulary you use at home with your children. The end point is that people are not randomly assigned to environments and, who knows, this self- selection may be partly genetic. Environmental factors are rarely independent of social/educational variables.
The current trend for research should be towards looking at mechanisms that affect the brain in autism from both the genetic and environmental perspective. This perspective emphasizes that autism is a neurological condition and that early interventions (behavioral techniques) work by changing the brain. Although controversial, I imagine that if we knew the mechanism underlying the effects of education on the brain we could bypass or significantly diminish the necessity of long hours of education training by directly modulating the underlying brain pathways. Educational experience could be enhanced and made available to all individuals in need of the same. The 20-40 hours necessary for ABA therapy could be reduced to 10 hours in a manner financially accessible to most parents.
The idea that early intervention (enriched environment) could have an effect in autism is an offshoot of the war on poverty started during the Johnson administration sometime in the 1960’s. It was said that early intervention could overcome the disparity in educational resources among social classes. Some programs like Head Start were a direct result of this movement.
In 1969 Arthur Jensen wrote what is probably the most influential article in the field of psychology: “How Much can we Boost IQ and Scholastic Achievement?” The article re-stated a popular theory stemming from Francis Galton whose “Hereditary Genius” claimed that intelligence was primarily an inherited trait. Both Galton and Jensen believed that genes were our destiny. Back then nobody had epigenetics in their mindframe. Jensen himself underestimated the potential of compensatory/early education. Although initial results from available programs at the time were counterintuitive and somewhat depressing, he never considered whether more intense efforts could make a difference. I think that having learned from this lesson ABA therapists/advocates, like Lovaas, started with the most intensive interventions and then lowered their required total number of hours according to research results.
It is still not known whether early intervention provides for changes in diagnosis or whether benefits are due to factors related to achievement, e.g. better social interactions, diminished behavioral problems, improved rates for entering mainstream schools (even college). And again we come back to the Nature-Nurture debate, how much can we achieve by interventions that only tackle one side of the argument? Taking broad brush strokes with either environmental or genetic research takes away the individuality of the patient.
Williams EL, Casanova MF, Switala AE, Li H, Qiu M. Transposable elements occur more frequently in autism-risk genes: implications for the role of genomic instability in autism. Translational Neuroscience 4(2):172-202, 2013.