Principia ætiologica: taking causality beyond Koch's postulates

Abstract

There is no single accepted method to establish a causal relationship between an infective agent and its corresponding infectious disease. Different biomedical disciplines use a patchwork of distinct but overlapping approaches. To a greater or lesser extent these are based on criteria known as the Koch–Henle postulates, or ‘Koch's postulates' for short. Deficiencies in Koch's postulates were recognized by their principal author shortly after their formulation. Now, over a century later, a more rigorous method to test causality has still to be finalized. One contender is a method that uses molecular methods to establish a causal relationship (‘molecular Koch's postulates'). Recognizing the wider range of contemporary approaches used to build an argument for a causal relationship, the use of a more inclusive approach to establish proof of causality is proposed. This method uses an argument built from a series of assertions. Assertion 1: congruence or reproducible correlation of a taxonomically defined life form with the clinico-pathological and epidemiological features of infection. Assertion 2: consistency of the demonstrable biological response in the subject to an encounter with the prospective infective agent. Assertion 3: progressive or cumulative dissonance as an explanation for pathophysiological processes at every known level of biological organization in the subject. Assertion 4: curtailment of that pathophysiological process on the deliberate introduction of a specified biomedical intervention. Evidence to implicate the candidate biological entity as an initiator of or primer for cumulative dissonance places it in a subcategory of micro-organisms to be known as ‘priobes’. A priobe is the sufficient and necessary antecedent cause of a pathophysiological process evident as an infectious disease.