Some causal limitations of pharmacogenetic concepts

Abstract

Pharmacogenetics and pharmacogenomics are related facets of cutting edge therapeutic research in a field that relates pharmacological properties to the genetic characteristics of human beings. An optimistic interpretation suggests that “One-Size-Fits-All” therapeutics, whose effects can only be predicted in probabilistic terms, will give way eventually to individual tailor-made therapies with entirely predictable properties in each patient. Yet the concept of anticipating individual pharmacotherapeutic response appears to disregard some of the fundamental limitations of causal understanding in the biological world of structure–action relationships. It is not simply a problem of confronting complexity – which might be overcome in time with advances in biotechnology and computing power – but the inescapable paradox of the genetic characteristics of individuals within the human species. The aleatory process of evolution ensures that with the exception of monozygotic twins, every human being is genetically unique. At the same time there appears to be more in common than divides. Pharmacogenomics provides a climate in which to explore and better understand the variable causal relationships between genetic element, protein and therapeutic or toxic actions, but can only do so in abstraction. Thus␣predictive power may be enhanced but is ultimately constrained by insuperable probabilistic considerations.