Rethinking the origin of chronic diseases

Since 1980, connections have been sought between chronicespecially autoimmunediseases and possible microbial actions that might promote or suppress immune responses. Here, we propose that the pathogenesis of some chronic diseases is linked to ancestral infections or exposure to noxious agents: Some modern-day diseases reflect the capacity of organisms to "memorize" responses to external signals and transmit them across generations; the resulting information can be subsequently made functional under certain conditions, through stimulation by a relevant secondary influence. The proposal is supported by observations of transgenerational epigenetic inheritance. Therefore, autoimmune hepatitis (AIH) could be a recollection of our ancestors' long-term affliction with viral hepatitis; the original causative agent may not be extant today, but "memory" of the infection has persisted. A similar argument could apply to other chronic diseases. In this article, we discuss evidence supporting this idea, with an emphasis on the exemplar pair of viral hepatitis and AIH, and outline a mechanistic hypothesis.