The Proto-Liver Origin of Life (PLOL) Hypothesis: A Metabolism-First Model of Prebiotic Regulation and the Ancestry of the Liver

Contact: via the website www.theliverbrain.com

The Proto-Liver Origin of Life (PLOL) Hypothesis proposes that life began when metal–organic catalytic clusters in mineral micro-pore environments self-organized into metabolic regulatory networks capable of buffering redox states, suppressing destructive reactions, stabilizing intermediates, and maintaining chemical gradients. These networks functioned as “proto-livers,” representing the first form of metabolic intelligence.

This regulatory-first model resolves long-standing contradictions in origin-of-life research by demonstrating how chemistry can self-stabilize without genetic information, membranes, or researcher intervention. It explains why universal metabolic enzymes preserve ancient iron–sulfur motifs, why metabolism is more conserved than genetic machinery, and why detoxification logic appears early in evolution.

The PLOL Hypothesis integrates geochemistry, systems biology, and evolutionary theory and provides explicit testable predictions. It reframes LUCA as a descendant of proto-regulatory networks and positions the modern liver as the evolutionary continuation of the earliest stable chemical architecture, with the brain evolving later as an extension of metabolic intelligence.