Pharmacogenomics: hype, hope, or metamorphosis of molecular medicine and pharmaceuticals

Pharmogenomics: The Search for Individualized Therapiesedited by Julio Licinio and Ma-Li Wong, Wiley-VCH, 2002. £40 (paperback) (559 pages) ISBN 3527303804In the past ten years, genomics has rapidly integrated into processes involving drug discovery, drug development and clinical outcome. The field of genomics is primarily fueled by automation in genomic technologies, which involve efficient, high-throughput data collection and analysis of genes, transcripts and proteins, thus allowing the generation of unprecedented quantities of biological information in the post-genomic era. The generation of these new data and their sub-categorization into different fields is often given an ‘-omic’ suffix. One of these is pharmacogenomics.Pharmacogenomics: The Search for Individualized Therapies is a timely publication that provokes a change in our grossly naive view of genetic determinism (that complex traits are caused by a single gene) to the obvious reality that most human diseases are complex entities: genes make a necessary, but partial, contribution to diseases, and environmental factors and lifestyles also impact gene epistasis.There is widespread indiscriminate use of the terms ‘pharmacogenetics’ and ‘pharmacogenomics’ but there is differential connotation of the two terms with no universally accepted definition, as described by Klaus Lindpaintner in this book. Pharmacogenomics is a science that addresses drug interactions at the genomic level, particularly in complex diseases with complex traits. The book discusses these complex paradigms and discusses how gene–drug interactions have combined effects on several single nucleotide polymorphisms (SNPs) in different genes. Furthermore, the book describes two main approaches taken to uncover pharmacogenomics markers, which include whole genome-linkage disequilibrium mapping and candidate gene studies, and shows concrete examples of linkage disequilibrium between markers located close together, affording an opportunity to examine combinations of SNPs, or haplotypes, within genes in diseases.The success rate of drugs is ∼70% with variable efficacy based on the genetics of the target protein and safety testing in animals, but a significant number of promising drugs fail to reach the market. Approximately 30% of patients treated with statins, 35% of patients treated with β-blockers, and 50% of patients taking tricyclic antidepressants show no response to therapy. More alarming is the fact that several of the individuals treated with statins have died. Furthermore, approximately 2% of statin-treated patients acquire musculoskeletal disorder and 15% of these patients now show non-reversible nerve damage. This book discusses how some of this susceptible population can be teased out to reap the benefits of the drug. Examples of responders, non-responders, and adverse drug effects in a pharmacogenomic environment such as cytochrome P450 2D6 trait variations among ethnic groups and increased risk of adverse drug reactions are discussed along with concise, updated tables on drug targets that are associated with disorder susceptibility.Dobzhansky has integrated population genetics theory with information on the distribution of variation within populations, similar to what Mayr did for systematics. A system approach or ‘wholistic biology’ approach for bioinformatics and data analyses for SNP analysis and/or gene expression array is required to decipher information acquired in pharmacogenomics. This is important because many modern biologists, both accomplished professionals and students, are ill prepared for this changing role because of the understandable bias in their background towards experimental techniques and results. It remains to be seen how able researchers interested in studying disease-associated polymorphisms and predictive medicine in particular groups of humans will manage these challenges.Although ‘ethics–societal aspects of pharmacogenomics’ are mentioned in the book, this issue is of great concern in areas of genomic-based translational research and could have been better addressed. Despite proposed international guidelines and institutional review board guiding protocols, there is no consensus on how to deal with these ethics–societal issues, which include informed consents and public acceptance, sample collection, secured sample storage, compensation for donors, sharing of biological samples for longitudinal studies, protecting links and electronic databases, etc. These are emerging concerns in the field as we go forward.The content of the book is intended to allow researchers from many different areas to find a starting point in the literature that is related to their areas of interest. The central messages of the book are genetics, race and medicine. The book is essential reading for students and scientists, rather than the public at large. Pharmacogenomics will bring genomics into the mainstream of sociobiology and to the general public at large; however, this is not addressed in the book. This field of pharmacogenomics is in its infancy, like a newborn falcon that shows hopes of quickly learning to soar in time and be part of our social structure.