Autism Research and Treatment pattern of central nervous system colonization during development suggest that these immune cells may have particular signiﬁcance in terms of neuroinﬂammatory eﬀects on developmental programming. Diverse early-life events may have enduring consequences for the brain and behavior of organisms via an inﬂuence on these resident immune cells, both by impacting their own intrinsic function as well as their interactions with ongoing developmental processes [40, 41]. 6. Approaching Autism as Another Member of the Family of Hyperimmune-Associated Diseases: Addressing the Underlying Causes The study of individual postindustrial associated diseases has often failed to enlighten researchers as to the underlying cause of diseases. While genetic factors associated with the epidemics of postindustrial society abound, these genetic factors have not changed over many generations, and thus are not responsible for newly emerging epidemics of disease. Almost paradoxically, even when speciﬁc triggers are iden- tiﬁed, these often cannot be said to cause newly emerging epidemics. For example, peanuts and ragweed pollen are two well-known triggers for allergy, but these substances have been present in the environment for millennia without triggering disease in humans. Similarly, viral infections and potentially some milk proteins [42] have been identiﬁed as triggers for particular autoimmune diseases, but these factors have been present for much longer than the diseases they trigger. Thus, as will be described in detail, it is not the genetics of the disease which point toward a cure, and it is generally not identiﬁcation of the triggers for disease that is most helpful. Rather, we suggest that the most eﬀective and insightful approach toward defeating autism for future generations will be the neutralization of underlying factors in postindustrial culture which render postindustrial humans uniquely susceptible to disease, despite the presence of the same genetics and many of the same triggers as found in preindustrial cultures. These factors have been identiﬁed as mismatches between normal human genetics and the environment of postindustrial culture. With that in mind, an examination of the factors in postindustrial culture which trigger the plagues of hyperimmune-associated diseases will be presented. 7. Mismatches between Normal Human Genetics and Postindustrial Culture Leading to Hyperimmune Epidemics: Biome Depletion If indeed autism ﬁts into the family of hyperimmune- associated diseases plaguing postindustrial culture, then the pathogenesis or origins of these diseases merit detailed analysis in any consideration of autism. As shown in Figure 1, postindustrial culture has several mismatches with normal human genetics (known as “evolutionary mismatches”) which have a profoundly destabilizing eﬀect on the human 3 immune system. This eﬀect is closely intertwined with an impact on metabolism and transport, as will be described later. These mismatches of postmodern culture involve some of the most cherished attributes of postmodern culture, including the widespread use of toilets, water treatment facil- ities, indoor working environments, soaps and shampoos, modern medicine, and the loss of factors which demand exercise for survival (e.g., human-eating predators, hardship in ﬁnding food and procuring shelter for most of the population). These mismatches are not a target for therapy, because reversal of any of these mismatches is untenable. Thus, these mismatches can be described as belonging to the “pretherapeutic zone” in the course of pathogenesis (Figure 1). However, these mismatches lead directly to readily measurable consequences that, in turn, lead to disease if left untended. Fortunately, these direct consequences of mismatches are readily treated or even avoided altogether. Given that these consequences can be treated or avoided, this part of the pathogenesis of hyperimmune disease can be described as the “optimal therapeutic zone” (Figure 1). In this paper we describe how mismatches between culture and genetics/biology have led to speciﬁc consequences which cause immune system hypersensitivity and/or destabiliza- tion. All of these consequences are associated with a wide range of diseases that include allergic, autoimmune, and inﬂammatory diseases. The single consequence of genetic/culture mismatches that most profoundly impacts hyperimmune-associated dis- ease has been described as a depletion of components from the natural ecosystem of the human body, or simply “biome depletion” (Figure 1). The use of modern medicine, toilets, water treatment facilities, and cleaning agents in our culture has led to a substantial alteration or even loss of living organisms that have coevolved with humans. Three primary components of the biome which are potentially important have been aﬀected [43]: (a) loss of interactions with soil bacteria, (b) alterations of the microbiome, the normal bacteria that are associated with the human body, and (c) loss of helminths, worms that typically inhabit the gut of mammalian species. Substantial evidence points toward all three of these factors as being important in stabilization of the human immune system. Although not widely appreciated, several lines of evidence point very strongly if not conclusively to the idea that helminths in particular are necessary for a stable immune system. This evidence has been reviewed extensively [1, 43] and can be very brieﬂy summarized as follows. (i) Helminths are found almost ubiquitously in prein- dustrial humans [44] and in nondomesticated mammals, including chimpanzees [45]. Even when helminths cannot be found, the immune system shows signs of stimulation by helminths [46]. (ii) Helminths produce and secrete a number of molecules which regulate the host immune system [47]. (iii) Addition of helminths to laboratory animals blocks allergic, inﬂammatory, and autoimmune diseases [47].