We Live, We Learn

By Phyllis Griffin Epps

Once upon a time, I approached pharmacogenomics as a thing removed from conventional medicine.  Faced with the prospect of “designer drugs,” my thoughts went to how those who fare worst under the current system would be affected.  I was concerned that the presence of such drugs ultimately would exacerbate disparities in health status, particularly disparities linked to ethnicity or “race.”  I imagined differences in single nucleotide polymorphisms, or SNPs, that were clearly linked to ethnicity and an ability on the part of industry to exploit these differences.  In short, I imagined a “new” danger that would raise new concerns.  I warned of a fever of misinformation that would breed resistance to the integration of genetics into the practice of medicine.

We live, we learn.

I overstated the extent to which polymorphisms of pharmacological significance occur disproportionately in different social groups otherwise described as “races”.  In so doing, I fell victim to the very dangers of misinformation against which I warned.  This occurred on several levels.

First, I am guilty of overestimating the extent to which complex disease is caused or explained by genes.  In this I am not alone.  It’s not that genes have a greater influence on health than environment; the former is new and exciting while the latter reminds us of how much we don’t know.  Namely, the combination/interaction of both that underlies many more diseases than the single-gene disorders like Huntington’s disease.

This is important because undue genetic essentialism can obscure the point: the treatment of disease.  In a recent issue of Science, Walter Willet discusses the dangers of emphasizing comprehension over treatment – missing the forest for the trees, you might say. Willett, W.C., Balancing Life-Style and Genomics Research for Disease Prevention, Science 296: 695-698 (2002). In a singularly enlightening essay, he suggests that treatment or even prevention of some diseases does not require full understanding.  Put another way, understanding may not lead us to treatment.  In predicting the integration of genetic information into clinical practice and the education of medical residents, Barton Childs reached a similar conclusion. Childs, B., Medicine Through a Genetic Lens, in IMPLICATIONS OF GENETICS FOR HEALTH PROFESSIONAL EDUCATION (M. Hager ed., 1999) at http://gnn.tigr.org/articles/12_00/Childs.pdf.   Such sentiments are at once troubling and useful because treatment and even prevention is the point.

Which brings one back to “designer drugs” and those on the losing side of disparities in health status.  The very phrase is misleading.  It suggests a stage of drug manufacturing and marketing that has not yet arrived. Rees, J., Complex Disease and the New Clinical Sciences, Science 296: 698-701 (2002).  Before pharmaceutical manufacturers or, for that matter, anyone else, understands the genome enough to make real sense of it all, knowledge about a person’s genotype will inform conventional drug therapy, by directing toward or away from a drug.  This suggests better health outcomes, which, again, is the point.

As for the need to reduce disparities that appear to populations traditionally defined as “races”, comprehension of the genetic role may not be as valuable as understanding how to control or manipulate the environment in ways that will prevent or facilitate treatment of a disease disproportionately present in some groups, like Type II diabetes.  Surely this serves the objectives of those on the losing side of disparities in health status.

I do not discount either genes or environment.  Neither would I presume to know the precise nature of interaction that might explain the differences in health outcomes experienced by different ethnic groups.  I do not mean to suggest that there will be “one answer” for everyone of a single population once described as one “race” or another.  I do mean to discount the specter of being left out of as-yet-nonexistent drug, tailored to the individual.  From the perspective of those who would ameliorate differences in health outcomes, particularly where the difference is related to the propensity of adverse drug reactions or even the lack of effectiveness of conventional drug therapy, we face questions more pressing than this.