6 Phase II components in what might be viewed as a tradeoﬀ between immunity and metabolism. In time of duress, when the immune system is geared to inﬂammation and defense, the energy devoted to metabolism/transport may need to be temporarily diverted to host defense. This is apparently an eﬀective strategy, but as a consequence, chronic immune activation could result in metabolic diﬃculties as outlined in Figure 1. Unfortunately, vitamin D deﬁciency is expected to make this problem worse, since vitamin D is required to upregulate both Phase I and Phase II components [85] of metabolism. Further, accumulation of toxins as a result of reduced Phase I, Phase II, or transport activity may also stimulate the immune system, adding further to the propensity for hyperimmune activity. 11. Implications of Autism as a Member of the Family of Hyperimmune-Associated, Postindustrial Diseases The implications of this model are several-fold and deserve careful consideration. The consideration of some possible assertions that are not supported by this model is probably equally as important. (i) This model indicates that prophylactic normalization of the biome will result in a profound decrease in the incidence of autism. Results with other hyperimmune-associated diseases have been promis- ing, although a true normalization of the biome as a means of prevention has never been attempted for any disease. (ii) This model is consistent with the idea that a variety of factors aﬀecting immunity and/or metabolism/ transport may strongly inﬂuence the incidence of autism. (iii) There are several potential therapeutic approaches that this model does not suggest which will necessar- ily be successful. For example, this model does not predict that helminths will necessarily work as a cure for autism. Whether helminths can be used to treat autism will depend on the extent to which autism is reversible and the extent to which ongoing problems with biome stability can be reversed. (iv) Although porcine whipworms are currently being used to treat the eﬀects of biome depletion in some studies, the model described in this paper does not predict that the porcine whipworm will prevent autism, even prophylactically. (Although the use of porcine whipworms is currently underway for a few clinical studies, the use of porcine whipworms as a means of prophylaxis is probably not economically feasible because the costs of giving the necessary biweekly doses would be prohibitive. This problem is not expected when using helminths adapted to humans, since one dose lasts for years.) It might, but this potentially depends on the extent to which this species recapitulates the presence of a normal biome. Autism Research and Treatment Thus, if porcine whipworms do not work, it does not suggest that the hypothesis is wrong. (v) This model does not suggest that helminths are the only organisms involved in biome depletion. Normalization of the microbiome may also be a critical factor. In the face of modern practices in obstetrics and of widespread antibiotic use, this is an issue that must be considered. (vi) Pharmaceuticals may never prove adequate. The complexity of the immune system and the eﬀects of biome depletion suggest that eﬀorts to readjust the system using drugs may be naive and overly opti- mistic. Biome reconstitution may be the easiest and most straight forward way to bring the system into homeostasis. Similarly, metabolic factors may not easily be compensated for by pharmaceuticals. Nor- malization and regulation rather than compensation and suppression are probably the better approaches. (vii) Genetics may be relatively unimportant from a clinical perspective because it may not provide a means to prevent or treat disease. Triggers may also be unimportant from a clinical perspective because (a) they may simply be unavoidable, and (b) even if triggers for a particular disease can be identiﬁed and avoided, such eﬀorts may simply decrease the prevalence of one disease at the expense of an increased prevalence of another. 12. The Required Approach Clinical trials are urgently needed to conclusively test a variety of questions. The approach needs to be extensive and systematic rather than timid and piecemeal. The tests required will be on a large scale, although this scale pales in comparison to the current amount of eﬀort and energy being poured into research on allergic, inﬂammatory, and autoimmune issues. This approach to medicine will not likely be supported by any committee of experts containing members with vested interests in traditional immunological approaches (either in humans or in rodents) or in the pharmaceutical industry. Rather, this approach is much more likely to be appreciated by those individuals with a broad understanding of biology and whose primary interest is in improving health care and, ultimately, the health of the population as a whole. With that in mind, the following questions need to be answered. (i) Can autism be cured or eﬀectively treated with biome reconstitution, or only prevented by biome reconstitution? (ii) How important for children is the biome of the mother prior to and during pregnancy, and while breastfeeding? (Does prevention require reconstitu- tion of the mother’s biome?) (iii) Which helminths or combination of helminths is both safe and eﬀective? Although some concerns dealing with the use of helminths for therapy have