From Pharmacogenetics and Ecogenetics to Pharmacogenomics

Abstract

The origin and development of pharmacogenetics are traced with emphasis on early hints by Garrod, Haldane, and later by RJ Williams. The field was delineated by Motulsky in 1957 and described as pharmacogenetics by Vogel in 1959. Kalow's monograph (1962) definitely established the discipline. Resemblance of identical twins in drug metabolism as compared with non identical twins (Vesell, 1970's) established the general importance of polygenic inheritance in disposal of many drugs. Ecogenetics was defined by Brewer in 1971 as dealing with genetic variation affecting the response to any environmental agents with emphasis on xenobiotics. More recent developments have broadened pharmacogenetic approaches to include novel genomic techniques with introduction of the term pharmacogenomics in the 1990's. Genetic and genomic approaches (toxicogenetics and toxicogenomics) are also being applied in the "environmental genome project". The interaction of genetic variation with dietary factors led to the field of Nutritional ecogenetics (Nutrigenomics) which relates the role of genetics to nutritional requirements and nutrition-mediated susceptibility to chronic disease. The total promise of pharmacogenomics is often overstated. The field is likely to have an impact on choice of drug therapy and avoidance of adverse events but is unlikely to lead to a revolution in therapeutics. Aspects of pharmacogenomic approaches and its applications including problems of premature commercialization are discussed.