NEJM as a counter-revolutionary running-dog:
nejm.org
Here are two excerpts from the introduction and conclusion (but you should really read the whole article):
On both sides of the Atlantic, revolutionary claims have been made about the ultimate impact of genetics on clinical medicine. John Bell at Oxford has asserted that "within the next decade genetic testing will be used widely for predictive testing in healthy people and for diagnosis and management of patients.... The excitement in the field has shifted to the elucidation of the genetic basis of the common diseases." (1) And in the United States the director of the National Human Genome Research Institute, Francis Collins, has stated that the good that would come from mapping the human genetic terrain "would include a new understanding of genetic contributions to human disease and the development of rational strategies for minimizing or preventing disease phenotypes altogether." (2)
Statements like these clothe medicine in a genetic mantle. The result of efforts to identify genes that have a role in common diseases suggests a different picture: the genetic mantle may prove to be like the emperor's new clothes. In this article we argue that the new genetics will not revolutionize the way in which common diseases are identified or prevented. Mapping and sequencing the human genome will lead to the identification of more genes causing mendelian disorders and to the development of diagnostic and predictive tests for them. The development of safe and effective treatments, however, will usually lag behind, (3) although occasionally a treatment does precede the discovery of the disease-causing allele, as was the case for hemochromatosis. (4) Furthermore, only a small proportion of the population has mendelian disorders, and this will limit the ultimate impact of the Human Genome Project.
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We do not want to downplay the importance of highly penetrant susceptibility-conferring genotypes or inherited drug sensitivity. Nonetheless, neither category represents a large enough proportion of the population to warrant widespread screening. (41) Testing in families with a history of the disease would be a more efficient approach but does not a revolution make.
It would be revolutionary if we could determine the genotypes of the majority of people who will get common diseases. The complexity of the genetics of common diseases casts doubt on whether accurate prediction will ever be possible. Alleles at many different gene loci will increase the risk of certain diseases only when they are inherited with alleles at other loci, and only in the presence of specific environmental or behavioral factors. Moreover, many combinations of predisposing alleles, environmental factors, and behavior could all lead to the same pathogenic effect.
In our rush to fit medicine with the genetic mantle, we are losing sight of other possibilities for improving the public health. Differences in social structure, lifestyle, and environment account for much larger proportions of disease (42,43) than genetic differences. Although we do not contend that the genetic mantle is as imperceptible as the emperor's new clothes were, it is not made of the silks and ermines that some claim it to be. Those who make medical and science policies in the next decade would do well to see beyond the hype.
I think their point is valid, but from my perspective they are missing the main issue - that treatments and drugs will eventually come from our understanding of genes and their expression. Once you understand just how a genetic defect causes a disease you are a big step along towards understanding the disease and finding a treatment, and further that treatment may well be different depending on your particular genetic makeup. Of course the article seems focused on detection and prevention rather than treatment.
A doctor friend of mine recently pointed out to me by way of caution that finding the genetic basis for a particular disease still leaves you a long way from finding an effective treatment - he cited cystic fibrosis as a good decade-old example.
Peter |
