Pharmacogenetics: past, present and future

The subject area of pharmacogenetics, also known as pharmacogenomics, has a long history. Research in this area has led to fundamental discoveries, which have helped our understanding of the reasons why individuals differ in the way they handle drugs, and ultimately in the way they respond to drugs, either in terms of efficacy or toxicity. However, not much of this knowledge has been translated into clinical practice, most drug–gene associations that have some evidence of clinical validity have not progressed to clinical settings. Advances in genomics since 2000, including the ready availability of data on the variability of the human genome, have provided us with unprecedented opportunities to understand variability in drug responses, and the opportunity to incorporate this into patient care. This is only likely to occur with a systematic approach that evaluates and overcomes the different translational gaps in taking a biomarker from discovery to clinical practice. In this article, I explore the history of pharmacogenetics, appraise the current state of research in this area, and finish off with suggestions for progressing in the field in the future.

Introduction

The term pharmacogenetics was coined by the German Pharmacologist Friedrich Vogel [1] in 1959, two years after Arno Motulsky [2] wrote his seminal paper on how ‘…drug reactions…may be considered pertinent models for demonstrating the interaction of heredity and environment in the pathogenesis of disease’. Pharmacogenetics can be defined as the study of the variability in drug response because of heredity. In 1997, Marshall introduced the term ‘pharmacogenomics’ [3]. Both terms are used interchangeably; however, the latter term, phamacogenomics, signifies that we have the knowledge and technology to evaluate the whole genome and we have the ability to interrogate multiple genes on drug response, rather than having to concentrate on a single gene at a time [4]. Although there are constant debates in the literature as to which term should be used, both refer to the need to improve the way we use drugs, to change the current ‘trial-and-error’ approach to one where we can be more precise as to how a patient is going to respond to a drug, where efficacy is maximised and toxicity is minimised. However, the transition from empirical approaches to better precision in drug therapy is not going to be easy, and will require a consolidated approach that will involve expertise from all sectors. It is also important to mention at the outset that genetics and genomics are not the sole determinants of drug response. Many other factors have to be taken into account including clinical and environmental factors. A combinatory approach evaluating all factors, including disease subphenotypes, is going to be crucial if we are going to succeed in personalising or stratifying drug therapy.