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Towards a systemic paradigm in molecular, evolutionary and biomedicine biology

Ernesto Burgio

In a brief article published on Bioessays in 1996, written on the occasion of Kuhn’s death, Adam WIlkins, wondered why in the twentieth century theoretical physics had faced its Kuhnian Revolution (from the Newtonian model to quantum mechanics and the theory of relativity) whereas biology had not yet experienced its paradigm shift. According to Wilkins, in fact, neither the Darwinian model in evolutionary biology, nor the Mendelian theories, nor even the DNA model described by Watson and Crick had paved the way for a real Kuhnian revolution in biology. A few months later, a well-known molecular biologist, Richard Strohman, replied to Wilkins by an article published on Nature Biotechnology: in short, Strohmann criticized the dominant reductionist model according to which the DNA would be considered as the store of the genetic program containing all the necessary and sufficient information for the construction of an organism (a linear model in which the information travels, so to speak, one-way, from DNA to proteins and phenotype). The essential meaning of my talk is an introduction to the increasingly necessary and urgent Kuhnian revolution of biology invoked by Wilkins and Strohman. The key words on which we will reflect are epigenome / epigenetics, microbiome / metagenomics, hologenome, connectome, all terms emerged in recent years that we should apply to better connect human and comparative biology, developmental biology and embryology, evolutionary biology and bio-medicine.  The main key-word in this context is certainly epigenetics: a term that has become fashionable in recent years, but which can be interpreted in various ways. The traditional one is the reductionist explanation, by which epigenetics is considered the part of genetics that studies how some specific marks on DNA and histones (the histone code) modulate chromatin’s shape, conditioning the expression of the genome. A very different model is emerging, by which epigenetics should be recognized as the most suitable and powerful tool to build the whole genome as a systemic, dynamic, fluid, unitary and interactive molecular network interacting with the environment. I will try to propose a model of genome in which the epigenome (which some have defined the software of the genome) behaves as a compensation chamber: the specific space where the flow of information coming from the outside meets the information that have been encoded for millions of years in the DNA (the hardware), orchestrating the main molecular processes that determine all the structural and functional changes of cells and tissues, causing the continuous transformation of the human phenotype (both physiological and pathological). We must think of these molecular changes as reactive and defensive mechanisms to environmental factors. As the genome is unremittingly and increasingly menaced by bad environmental factors, the (epi)genome is forced to mutate in a reactive and defensive way. However, at a certain point, if the environment changes too fast compared to the ability of the (epi)genome to adapt all these molecular changes become dangerous for the single organism. Pathologies do not occur by accident: they are the product of this epigenetic instability and even DNA mutations should be seen as the consequence of this instability.

 Wilkins AS. (1996). Are there ‘Kuhnian’ revolutions in biology? Bioessays 18:695–696