The quantitative and qualitative differences of circulating nucleic acids (cirNAs) between healthy and diseased individuals have motivated researchers to utilize these differences in the diagnosis and prognosis of various pathologies. The position maintained here is that reviewing the rather neglected early work associated with cirNAs and extracellular vesicles (EVs) is required to fully describe the nature of cirNAs. This review consists of an empirically up-to-date schematic summary of the major events that developed and integrated the concepts of heredity, genetic information and cirNAs. This reveals a clear pattern implicating cirNA as a homeostatic entity or messenger of genetic information. The schematic summary paints a picture of how cirNAs may serve as homeostatic genetic entities that promote synchrony of both adaptation and damage in tissues and organs depending on the source of the message.
Keywords: Bystander effect; Circulating nucleic acids; Extracellular vesicles; Genetic homeostasis; Genometastasis; Metabolic DNA.