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RESEARCH PRODUCT

Darwinism and pharmacogenomics: from 'one treatment fits all' to 'selection of the richest'?

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Pharmacogenomics and pharmacogenetics are relatively new fields, and have arisen from recent advances in genetic research. They offer new perspectives on the development of pharmaceuticals, allowing drug design to be targeted specifically to the genotype of selected populations. The discussion of who will be considered for the development of these tailored drugs and who will be excluded, in a situation in which both research resources and public expenditure are limited, is provoking and has led to several, still unanswered ethical questions and concerns about fairness and the potential discrimination of fringe groups. Based on the statistical analyses of population averages, patient groups are generally assumed to be homogenous. Treatment is generally given according to empirical, if not arbitrary, guidelines, often ignoring potential discrepancies in drug response. Drug therapy is targeted, therefore, to the broadest possible patient population. In view of the increasingly aging population in the western world, socioeconomic expenses for both treatment and adverse drug reactions are booming, whereas public spending is progressively under pressure. Disparities in responses to drugs are common among patients and represent a significant clinical problem. These disparities might, at least in part, result from genetic variations among individuals or populations. A drug that is well tolerated and elicits a good response in some patients might be ineffective, toxic or cause severe adverse events in others. Drug response might, of course, also depend significantly on the underlying condition being treated and could be influenced by concomitant medications and drug interactions, by patient age, sex, organ function, lifestyle, education, socioeconomic status, environmental factors and accompanying illnesses. However, many of these factors are difficult to control for and are likely to be affected by a person’s ethnic background [1,2]. Insurance works by sharing risk: the greater the risk, the higher the premium. As long as risk is equally uncertain for everyone, all insured members are asked to contribute equally to the insurance pool. If, however, different groups are at different risk, which might be the case, the more genetic disorders that are known and the more predictable the response to treatment, then individuals with a lower risk will insist on the lower risk-adapted payments and on the disclosure of private genetic information. Conversely, premiums for groups being at greater risk will rise and insurance might potentially be denied to those whose genes predict extended or expensive medical treatment. The public acceptance of pharmacogenomics, which studies genetic polymorphisms underlying the variations in drug response between individuals and individual populations, is, therefore, high because it promises individualized safe and effective treatment at lower cost [3]. Therefore, pharmacogenomics not only has an impact on the individual, but also affects whole population groups and the pharmaceutical industry. Because pharmacogenetic testing is expected to be expensive at first, it is likely to be accessible only to those who can afford both the test and the designer drug best suited to them. Companies work for profit; therefore, genotypetailored drugs will be targeted primarily for mass production to the benefit of financially sound, large, genetically homogenous populations and diseases. These circumstances will, of course, provoke numerous conflicts of values and interests, because population groups who cannot benefit or who are likely to suffer from side effects will potentially be left out, awaiting the development of new subsets of drugs that are tailored specifically to their genotype [4–6]. These populations will either be left untreated or will be treated according to the one treatment fits all policy. Many generations of researchers have tried to arrange populations on the basis of geographical, ethnic or racial characteristics and to correlate them with behaviour or intelligence, with diseases or genetic patterns and, more recently, with the phenotypic inter-individual variation of drug-metabolizing enzymes. Not surprisingly, several clinical studies have now reported differing drug responses among ethnic groups, thereby reinforcing the idea that biological differences underlie the social concept of race [1,7,8]. Discrimination on the basis of on an individual’s overt phenotype has occurred for thousands of years and has, unfortunately, also had a sad impact on medicine. Despite remarkable progress and promises resulting from pharmacogenomics, which provide options for preventing and treating inherited disorders, and avoiding adverse drug reactions, strict international regulations to the benefit of all parties involved, which avoid discrimination and prevent harm from society, industry, groups or individuals, are urgently needed. Pharmacogenomics will take us to a new level of transparency in patient care and in the management of economic resources. The availability of genetic information is Corresponding author: Ulrich Mahlknecht (Ulrich_Mahlknecht@med.uniheidelberg.de). TRMOME 145