Peter,
Then I guess I'm the moderate caught in the middle.
nejm.org
brings up some of the issues that the most fervent genomics boosters and bankers with SNP IPO's to float fail to ever mention. There is much hype about the promise of genomics/genetic medicine, and the market will at some point make them/us pay for it. Most of that hype, however, will be true (IMO), eventually. The problem for investors will be the ever so often repeated disconnect between medical science timelines and the market's expectations.
The ultimate premise of this opinion piece is that genomics will only matter to a small percentage of patients, and on this I see classic myopia. Put simply, people who've spent the better part of 30-50 years learning what they know just seem to refuse to accept that more will be accomplished in the ensuing decade than in those prior decades (even though they themselves experienced that same phenomena). The rate of technological advance is almost always accelerating (and at least during the 20th Century, dramatically).
Thus:
<Selectively snipped, reader beware>
Searches for susceptibility-conferring genotypes for breast cancer, colon cancer, rare, early-onset forms of type 2 diabetes, and Alzheimer's disease have been successful, but in each case these genotypes account for less than 3 percent of all cases. One explanation is that the risk of disease conferred by alleles at one locus depends not only on alleles at other, independently segregating loci, which by themselves do not increase the risk, but also on environmental factors. The problem of identifying susceptibility-conferring genotypes is compounded when different combinations of gene loci are implicated in a disease, for it means that finding enough patients to serve as research subjects in a study will be extremely difficult.
The first two-thirds of this paragraph are more an argument for bioinformatics than a damnation of genetic medicine. The argument that, "Oh, it's too complicated to figure out," has always made me see red. Yes, it's going to take some hard work and some significant advances in bioinformatics/pattern recognition/AI to do, but IMO we will see this accomplished in this decade (or sooner). The authors may be trying to give themselves an out by limiting the term "genotype" to denote the alleles that a person possesses at a single gene locus on homologous chromosomes.
The last sentence of the paragraph does point out one of those things that the most rabid promoters of genetic medicine fail to, the recruitment of rare alleles into clinical trials and research studies, but I have the suspicion that we'll find solutions.
Inherited differences in sensitivity to drugs may be more amenable to pharmacologic tailoring than differences in susceptibility to disease. Determining patients' genotypes before they are given certain drugs may lead physicians to avoid administering drugs that could be harmful or to lower the dosages in sensitive patients, but the overall risk of adverse reactions may not be very high because of the low penetrance or low frequency of the genotypes. Alternatively, patients could begin taking a drug, be carefully monitored, and undergo genotyping only after an adverse reaction has occurred. This approach has been recommended for women in whom deep-vein thrombosis develops while they are taking oral contraceptives and who may have a susceptibility-conferring genotype at the prothrombin gene locus.
They seem to want to ignore the potential for determining a priori probable efficacy in patients, or for even a panel to identify probable pharmacokinetics for an individual patient for a variety of pharmaceutics. Wonder what the authors would have said about antibiotic sensitivity panels two decades ago?
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.
Once again, "Oh, it's too hard." Bottom line, it's all about economics. While a genotyping panel is several hundred/several thousand dollars and we don't have the algorithms to interpret it, they're right, uptake will be slow. But by the end of this decade, when a panel is a hundred dollars or less and comes with an interpretation, we can put this next to some of the early quotes about the PC. This is fundamental medical information, as we (and physicians) learn to use it and the cost of acquiring it comes down, it will become standard. All IMO, of course.
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 than genetic differences...Those who make medical and science policies in the next decade would do well to see beyond the hype.
Ah, now I see, scared that their grant money will dry up...
biowa |
