Saturday, February 16, 2008

NEJM Article on Genomic Variation and Personalized Medicine

The latest issue of the New England Journal of Medicine has this interesting article by Charles Lee and Cynthia Morton entitled "Structural Genomic Variation and Personalized Medicine". The article appears in the section for "Clinical Implications of Basic Research". The authors note the importance of this recent study which revealed that the almost exclusive attention given to qualitative differences in the genome is unwarranted. As Lee and Morton note, "quantitative differences, such as deleted and duplicated genomic sequences, and large-scale rearrangements (collectively referred to as structural genomic variant architecture) are just as — or more — relevant".

These empirical insights have important implications for an account of genetic justice. For example, in this recent paper I argued that genetic inequalities were qualitative rather than quantitative inequalities. Well, now I know this is not the case after all (though I think it is safe to say that this was the standard scientific view at the time I actually wrote the article!). And so this empirical fact is worth noting as it could impact our determination of what kind of intervention is required (e.g. one that remedies qualitative versus quantitative differences). And it is precisely these kinds of discoveries that have lead me in the direction of arguing that the demands of genetic justice are provisional- they are open to new moral insights and empirical discoveries. Furthermore, I don't think these issues necessarily undermine or pose a serious problem for the central principle of genetic justice I defend. That is, the lax genetic difference principle which states that genetic inequalities (important to the natural primary goods) are to be arranged so that they are to the greatest reasonable benefit of the least advantaged.

Here is a sample from the NEJM article:

The ultimate goal of personalized medicine is to comprehensively identify genetic differences among persons and to correlate specific genetic features (or combinations of genetic features) with the differential risk of human diseases or the efficacy of certain therapeutic interventions. This goal is likely to be achieved when we are able to identify all relevant forms of genetic variation in each person and are able to interpret this information in a clinically meaningful manner.

The Human Genome Project revealed a very high degree of similarity between the DNA sequences of any two persons. These similarities unite us as a species. On the other hand, the differences in our DNA sequences (combined with the effects of our environment) make each one of us unique. Until recently, qualitative differences in the genome — in the form of single-nucleotide polymorphisms — have enjoyed the limelight. However, a recent study by Korbel and colleagues1 reinforces the notion that quantitative differences, such as deleted and duplicated genomic sequences, and large-scale rearrangements (collectively referred to as structural genomic variant architecture) are just as — or more — relevant.

....Physicians may eventually be able to use a person's genetic-variation profile to determine the optimal intervention for the patient's condition (Figure 1), although such a strategy will depend on genetically informed clinical trials. Of course, there will continue to be a struggle to provide this type of information so that a patient and a physician can make informed health-related decisions, while minimizing its effect on insurance-related discrimination. Nevertheless, we are currently witnessing an exciting discovery phase in human genetics that will undoubtedly affect the way physicians ultimately practice medicine.