An Energy-Based Model of Biological Experience Tested in Computational Models and in Human Cells

Jack Devine

Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, New York, USA

Tuesday, October 13 · Poster Session 1 · Mission Bay Room

Poster

Jack Devine, Calvin Bradbury-Jost, Nirosha Murugan, Martin Picard

Jack Devine — Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, New York, USA
Calvin Bradbury-Jost — Department of Health Sciences, Wilfrid Laurier University, Waterloo, ON, Canada
Nirosha Murugan — Department of Health Sciences, Wilfrid Laurier University, Waterloo, ON, Canada / The Allen Discovery Center, Tufts University, Medford, MA, USA
Martin Picard — Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA / Robert N Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA / New York State Psychiatric Institute, New York, NY, USA / Department of Neurology, H. Houston Merritt Center, Columbia Translational Neuroscience Initiative, Columbia University Irving Medical Center, New York, NY, USA

Biological organisms are the only systems that we know to be conscious. The fundamental difference between a living organism with experiences and a dead one is the flow and transformation of energy. Sustained energy transformation takes place through a series of reactions known as metabolism. In eukaryotic cells, including humans and all animals, dozens of metabolic pathways converge on mitochondria, small cellular organelles (100-1000’s per cell) that transform food and oxygen into usable energy forms to sustain life. Therefore, energy metabolism in general, and mitochondria in particular, may be important to understanding how experience arises in living organisms. The energy resistance principle (ERP) offers a mitochondria-centered principle which outlines how energy flows and is transformed in living organisms. In short, the ERP states that the resistance to energy flow, or the inverse of conductance, enables energy transformation and patterning. The ERP outlines how two factors: the system’s energy potential (EP) and energy flux (f), relate to generate energy resistance (EP/f2=éR). In this formulation, if éR is zero, there is no life. Non-zero éR allows not only life, but also expressions of life, including subjective experiences. All sensory experiences require the transduction of energy from one form into another. From the perspective of the ERP, a conscious mind is a dynamic energy pattern, for which cellular and molecular structures constrain energy flow, and thus provide the resistance required for experience to emerge. Thus, the ERP may offer insights into the origin of experiences. To begin testing this framework, we examine ERP-derived predictions in silico using ordinary differential equation-based models of mitochondrial metabolism, and in vitro leveraging primary human fibroblast cell lines. The initial prediction in both models is that éR indexed as the system’s redox marker (NADH/NAD+) and secreted protein marker (GDF15) will increase as we elevate EP, and decrease as we elevate f. Data from the literature and preliminary evidence in our models support these predictions. The ERP provides a principled approach to explore experience from an energetic lens, predicting that changes in éR will track with changes in the experience of organisms.