Autism Research and Treatment been expressed, these objections are easily dealt with [1]. Several candidate species are well adapted to humans, asymptomatic in low numbers, and thus are obvious candidates for initial and immediate test- ing. Further, new technologies might be developed which could improve on species that are naturally occurring. For example, irradiation of organisms to achieve sterility and eliminate the possibility of trans- mission, or cultivation of human-speciﬁc helminths in ultraclean and immunodeﬁcient rodents or even in vitro might improve the utility of helminths for widespread medical use. (iv) What medical conditions such as a suppressed immune system, anemia, or coagulopathy might be contraindications for biome reconstitution? (v) Does optimal biome reconstitution vary with human genotype or other factors such as age, gender, and body size/composition? (vi) In addition to the restoration of helminths to the biome, what steps should be taken for restoration and maintenance of the microbiome? (vii) How will a reconstituted biome aﬀect other areas of medicine, including aging, immunosuppression, infectious disease, cancer biology, and vaccine tech- nology? 13. Is Autism a Postindustrial, Hyperimmune-Associated Epidemic? The idea that autism is a result of evolutionary mismatches is predicated on the idea that autism is epidemic in postin- dustrial society. Thus, if the incidence of autism is the same in preindustrial societies as it is in postindustrial societies, then biome depletion is not a factor in the pathogenesis of autism, and biome reconstitution will not aﬀect the incidence of autism. The epidemiology of autism has been hotly debated. Some changes in diagnostic criteria and awareness of autism have certainly aﬀected changes in the reported incidence of autism over time. However, debates regarding the changing diagnosis of autism over the past few decades have little bearing on the idea that biome depletion profoundly inﬂuences autism. Rather, the pertinent question is whether the prevalence of autism has changed over the past 150 years as various cultures have transitioned from pre to postindustrial over the course of several generations. Although it may be very diﬃcult if not impossible to estimate the prevalence of autism prior to the industrial revolution in countries that are currently postindustrial, it might still be possible to examine the prevalence of autism in some preindustrial societies. One very recent study by Schieve et al. is particularly informative in this regard: using a phone survey technique to obtain data on 4,690 Hispanic children, a “striking heterogeneity” in the prevalence of autism spectrum disorder between US-born Hispanic children with 2 US-born parents (autism spectrum disorder prevalence 2.39%) and otherwise similar children with 2 foreign- born parents (autism spectrum disorder prevalence 0.31%; 7 P = 0.05) that autism is a consequence of evolutionary mismatches in postindustrial society and is consistent with the idea that the parental immune status is important in the development of autism. Further assessment of autism in preindustrial cultures may, however, prove unnecessary; the easiest way to evaluate the idea that autism is related to biome depletion is probably to conduct the experiment. Whether prophylactic biome reconstitution does or does not aﬀect the incidence of autism will answer all questions conclusively, just as the eﬀects of biome reconstitution [49, 87] and vitamin D supplementation [88] on multiple sclerosis, if conﬁrmed by future studies, will eﬀectively end long-standing debates about the etiology of that disease. The idea that autism is a result of evolutionary mis- matches is predicated on the idea that autism often occurs in genetically “normal” individuals. Thus, if autism can be attributed to genetic factors which dictate the presence of disease even in individuals living in a preindustrial society, then biome depletion is probably not a factor in the pathogenesis of autism, and biome reconstitution will probably not aﬀect the incidence of autism. Certainly there are cases where autism is associated with genetic mutations which are deleterious, such as fragile X syndrome, but at present most individuals with autism appear genetically normal [89]. However, it remains unknown what percentage of autism can be attributed directly to genetics, and the idea that biome depletion and other evolutionary mismatches aﬀect mutation rates is speculative and unexplored. Again, the most eﬀective approach to resolving the debate regarding the role of genetics may be to prophylactically reconstitute the biome of a sample population and await the results. The epidemiology and the genetics of autism are inextricably woven together. It is anticipated that one of two pictures will emerge. Either a postindustrial epidemic of autism with normal genetics will be identiﬁed, or autism will be eventually deﬁned as a “normal” part of the human condition, potentially associated with certain genes or combinations of genes that predispose to disease regardless of the environment. In the former view, autism is due to an evolutionary mismatch, whereas in the latter view, autism is due to evolution itself. It is of critical importance not to accept the latter view prematurely since such acceptance may disable eﬀorts at compensating for evolutionary mismatches or discourage work on identifying postindustrial triggers for disease, with potentially tragic consequences. Fortunately, several lines of evidence argue against the idea that autism is a “normal” part of human biology. First, a general consideration of the nature of human evolution argues that evolution is not responsible for autism. The social interactions disrupted by autism are fundamental to survival of not only humans, but also a wide range of mammalian and nonmammalian species, pointing to the ancient evolutionary origins of those interactions. Given the intense selection pressures on early human populations, it seems unlikely that an error rate of 1% in social interactions would have developed and then persisted for many tens of thousands of years. However, the idea that autism was tolerated during human evolution because it is essentially a tradeoﬀ, an inherent “side-eﬀect” of human brain function