Epigenesis and self-organization: new perspectives in Biology and Medicine

The paradigm of DNA as a genetic program has reached its limits and a new p aradigm is emerging, where DNA can be looked lather as data processed by th e cellular machinery network, working itself as a parallel distributed prog ram with properties of self-organisation and learning. As usual in the hist ory of science, experimental evidence for the new paradigm is coming from r ecent discoveries which,were made possible only by the techniques developed within the framework of the ancient paradigm. comparative analysis of geno mes, prion and prion-like phenomena, epigenetic inheritance, " reprogrammin g " of differenciated genomes by nuclear transfer: The new paradigm may be characterized as follows : i) proteins are coming buck as carriers of biolo gical information not reducible to DNA structure; ii) the picture of a unid irectional flow of information from genes to proteins and functions is repl aced by a more balanced but more complex picture of interactions between ge netic and epigenetic determinations, modulated by the geometrical, biochemi cal and ionic micro-environments of the cellular structure; iii) this pictu re is more adequately described by the formalism of complex dynamic systems than by the usual metaphor of a computer program. The role of ion transpor t in signal transduction is a particular instance of such a centriperal flo w of information. New, data on the effects of the Na+K+Cl-cotransport on th e cellular metabolism regulation are reported. In addition to its role in c ell volume re regulation, this transporter is part of a second messenger sy stem activated in cell division. Moreover, overexpression of its gene induc es a typical proliferative transformation of the cells, accompanied with an overactivation of a MAPkinase-dependent pathway. This results indicates th at a gene coding for a transmembrane ion transporter may exhibit oncogenic properties. Immunotherapy for autoimmune diseases is another field[ where n etwork analysis is being applied, with planned clinical trials in progress.