How to gain evidence for causation in disease and therapeutic intervention: from Koch’s postulates to counter-counterfactuals

Abstract

Researchers, clinicians, and patients have good reasons for wanting answers to causal questions of disease and therapeutic intervention. This paper uses microbiologist Robert Koch’s pioneering work and famous postulates to extrapolate a logical sequence of evidence for confirming the causes of disease: association between individuals with and without a disease; isolation of causal agents; and the creation of a counterfactual (demonstrating that an agent is sufficient to reproduce the disease anew). This paper formally introduces counter-counterfactuals, which appear to have been used, perhaps intuitively, since the time of Koch and possibly earlier. An argument is presented that counter-counterfactuals (disease-preventers) are a useful tool for identifying necessary causes of disease, and sometimes must be used in place of isolation which is not always possible. In addition, a logical sequence of causal evidence for a therapeutic intervention is presented: creating a counterfactual (demonstrating that the intervention is sufficient to change the natural course of a disease), comparisons between subjects in receipt of treatment versus those who are not (typically within a randomised controlled trial, which can quantify effects of intervention), and counter-counterfactuals (treatment-preventers, which can identify the intervention’s mechanisms of action).