8 that is required for survival, cannot be ruled out. A second line of evidence pointing in favor of autism as a result of evolutionary mismatch rather than evolution is the study, described above, showing that parental birth in a postindustrial culture seems to predispose oﬀspring to autism [86]. Third, the observations (a) that the immune system is profoundly destabilized by postindustrial culture and (b) that brain development is closely tied with immune function, when considered together, argue strongly for the idea that it is an evolutionary mismatch, not evolution, which is responsible for autism. Indeed, to the extent that human brain development is strongly tied to the immune system, it would be diﬃcult to explain the idea that postindustrial culture and the resulting consequences of evolutionary mismatches such as biome depletion do not profoundly aﬀect brain development. Finally, the strong association of autism with autoantibody production [3] and other immune abnormalities points toward the etiology of autism as straight forward: another epidemic in the long list of hyperimmune associated epidemics caused by biome depletion in postindustrial society. The fact that this particular disease aﬀects primarily the brain rather than other organs or tissues undoubtedly leads to the tremendous complexity in the pathology associated with autism, but this complexity should not blind the medical community to the simple roots that apparently underlie epidemics of all allergic and autoimmune diseases, or to the apparent solutions that can currently be implemented to prevent those diseases [1]. 14. Summary/Conclusions Autism has many of the characteristic features of hyperimmune-associated diseases which result from biome depletion and other consequences of biology/cultural mismatches in postindustrial culture, potentially sharing a common cause and potentially a common solution with those diseases. The identiﬁcation of triggers for autism (e.g., association with viral infection during pregnancy [90]) parallels that of other diseases in this family. However, the trigger that causes disease is often unrelated to the cultural mismatches with human biology which destabilize the human biome and make the trigger dangerous. The association of autism with genetic and probably epigenetic factors also parallels that of other hyperimmune-associated diseases, but oﬀers little in the hope of prevention, treatment, or a cure. The ecosystem of the human body, the human biome, is a tightly interwoven collection of factors which includes immunity, brain function, sunlight, hormones, metabolism, transport of metabolites, the microbiome, and helminths. It stands ﬁrmly to reason that if one or more of these com- ponents are profoundly altered or even deleted, the entire system may become destabilized. This view of ecosystems has long been appreciated by ecologists [91]. Although some hyperimmune diseases might be eliminated if the respective triggers for those diseases are identiﬁed and avoided, such as approach cannot be successful in eliminating the overall problem; roughly 50% of children in postindustrial society have some form of chronic health condition [92], many Autism Research and Treatment millions are aﬀected by a wide range of allergic, inﬂam- matory, and autoimmune disorders, and inﬂammation as a result of biome destabilization may play a key role in such common maladies as heart disease and dementia. With that in mind, the need for normalization of the biome cannot be overemphasized, regardless of particular diseases that might be prevented by identifying and avoiding the environmental trigger. Thus, while it is hoped that a trigger that causes autism might be conﬁdently identiﬁed in the near future, and new cases of autism might be greatly reduced as a result, it is hypothesized that normalization of the human biome will be necessary to avoid the full milieu of chronic immune-related diseases that plague postindustrial society. Acknowledgments The authors gratefully acknowledge the contribution of the Research Coordination Network in Ecological Immunology for facilitating discussion, and the Coalition for SafeMinds for providing the publication fee. The authors also thank Sharon L. Brenner, Zoie E. Holzknecht, and Susanne Meza- Keuthen for helpful discussion. References [1] S. D. Bilbo, G. A. Wray, S. E. Perkins, and W. Parker, “Reconstitution of the human biome as the most reasonable solution for epidemics of allergic and autoimmune diseases,” Medical Hypotheses, vol. 77, no. 4, pp. 494–504, 2011. [2] V. T. Ramaekers, N. Blau, J. M. Sequeira, M. C. Nassogne, and E. V. Quadros, “Folate receptor autoimmunity and cerebral folate deﬁciency in low-functioning autism with neurological deﬁcits,” Neuropediatrics, vol. 38, no. 6, pp. 276–281, 2007. [3] G. A. Mostafa and L. Y. Al-Ayadhi, “The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children,” European Journal of Pediatric Neurology. In press. [4] P. Ashwood and A. J. Wakeﬁeld, “Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine proﬁles in children with autism and gastrointestinal symp- toms,” Journal of Neuroimmunology, vol. 173, no. 1-2, pp. 126– 134, 2006. [5] P. Ashwood, S. Wills, and J. Van De Water, “The immune response in autism: a new frontier for autism research,” Journal of Leukocyte Biology, vol. 80, no. 1, pp. 1–15, 2006. [6] R. L. Blaylock, “A possible central mechanism in autism spectrum disorders, part 2: immunoexcitotoxicity,” Alternative Therapies in Health and Medicine, vol. 15, no. 1, pp. 60–67, 2009. [7] R. L. Blaylock and A. Strunecka, “Immune-glutamatergic dysfunction as a central mechanism of the autism spectrum disorders,” Current Medicinal Chemistry, vol. 16, no. 2, pp. 157–170, 2009. [8] N. C. Derecki, E. Privman, and J. Kipnis, “Rett syndrome and other autism spectrum disordersbrain diseases of immune malfunction,” Molecular Psychiatry, vol. 15, no. 4, pp. 355–363, 2010. [9] A. M. Enstrom, C. E. Onore, J. A. Van de Water, and P. Ashwood, “Diﬀerential monocyte responses to TLR ligands in children with autism spectrum disorders,” Brain, Behavior, and Immunity, vol. 24, no. 1, pp. 64–71, 2010.