The Electronome: The New Central Dogma Of Biology
We have long sought to understand biology through the central dogma of biology proposed by Sir Francis Crick in 1952. The central dogma of biology – where understanding DNA, RNA, and Protein structures as the key information architecture of biology may just be at the wrong level of abstraction to predict exactly what happens in biology.
The electronome is a concept that may just upend all of this, which is that electrical patterning acts as a type of molecular informational memory to guide the goal of cells, organs, organisms in a holistic way. Rather than being defined at the hardware level – like genes, molecules, and proteins, the electronome is defined at the software level - at the voltage level, where patterns of changes in electrical signals serve as the blueprint for the goal of a collection of cells. In a single cell electrical voltages are generated by the passage of Sodium and Potassium ions across the cell membrane via Ion Channels, and then this information is communicated to adjacent cells via gap junctions. The resulting system of ion channels, whose output can be changed by shifting the distribution of ions and the resultant electromagnetic changes at the cell level, cascade through collections of cells via gap junctions creating an emergent informational architecture which communicates at the cell level, the tissue level, the organ level and the organism level in an elegant hierarchical way. As such changes in the software or voltage level can cascade down resulting in a different molecular outcome. This is striking because it suggests a new way for biological information to flow where changes in the electronome can generate changes in the molecular level, even with an identical genome.
What I find elegant about this idea is that it explains a number of biological phenomena - for example cancer can be described as a situation where a cancer cell loses electrical congruence with its neighboring cells, and hence acts in isolation. In experiments in xenopus levi, an overexpression of p53 in a particular location induced tumorigenesis, but the expression of the cancerous cell was kept in check by simply changing the electrical signal at the local level to maintain the pattern memory that bound the cell to its neighbours. This is striking because a change in the electrical voltage at the local level by manipulating ion channels can keep cancer in check.
In regenerative medicine if we want to stimulate the regrowth of an organ, we can restimulate the cells using the same pattern memory of electrical signals meaning we can regrow a leg or an arm or a finger back in the pattern that the organ already had. The changes in the electrical memory reminds the cells to regenerate in the pattern required of them before the organ was removed. Also developmental events like how embryos mature or reversing birth defects can have similar impact through manipulation of electronomic signals. In aging – we move between different morphogenetic states from childhood to adulthood to old age. Can we remind our cells to act like the pattern of the previous morphogenetic state to stimulate repair and reverse aging. In infectious disease pathogens may manipulate electrical signalling in order to manipulate cells into differentiating differently - so can we explain infectious disease or the impact of the microbiome on our health through the lense of the electronome?
And further afield – environmental stressors which create trauma – may also be mediated through changes in the electronome which lead to molecular changes leading to stored stressed states in our nervous system. Can electrical repatterning reverse these signatures?
In conclusion – the elegance of the ideas behind the electronome – from the details of how ion channels and gap junctions generate and propagate electrical signals, through how these cascade hierarchically through cells and organs - and can explain phenomena as diverse as cancer, developmental biology, infectious diseases, aging and even trauma warrant deep investigation as a topic. The electronome could be a new way to understand biology and the information that is encoded at the software level rather than the hardware level.
