Monday, July 27, 2009

Ethical issues in personalized 'genomic' medicine

Ken was just at a very interesting conference on ethical issues that will pertain to the use of genomic data to 'personalize' medicine in the 21st century. Of course, all such conferences are presumptuous in the sense that nobody can really know what things will be like. The record of pundits and experts (scientific, economic, or political) is so poor it's a wonder there is employment for any of us. In biomedicine and genetics, we've made so many false promises that if we were Pinocchio we'd all be sprouting giant Sequoias for noses.

Nonetheless, using individual genotypes to try to predict or diagnose disease is going to be a fad for at least some years until it either proves to be a bonanza for health care, or a bust with little definitive power. So much effort is going to be invested in the effort, that if it doesn't pay off it will be for good reasons -- that is, we'll have learned a lot about biology in the process of not improving medicine very much.

Likewise, if individual genotypes do prove to be of high predictive or diagnostic value, that will mean we know the genes and hence will be able to figure out why they lead to disorders and then, presumably, we'll be able to engineer some prevention or therapy.

'Personalized medicine' is a lobbying phrase in that medicine has always been personalized, and adding the term 'genomic' is also a lobbying phrase for support to attempt to boil your and my health (and who knows what else?) to estimable, powerful genetically based effects. The fact that's it's a catch-phrase to sell personal direct to consumer genetic advice, or other clinical or commercial products, does not mean it's bad or won't work. But at this stage, we need to be aware of the vested-interest component. In principle (but not in America), we could keep quiet until we actually knew it would work before we started selling predictive genomic services.

In fact, there are many traits for which an aberrant gene is indisputably known. Many investigators are working on trying to understand them. They are the 'Mendelian' diseases that are almost always due to aberrant function in the same gene (like cystic fibrosis or sickle-cell anemia), and fractions of more complex diseases in which some cases are due to a single gene (like breast cancer associated with mutations in the BRCA1 and 2 genes) but most cases aren't. Personalized medicine, whether predictive, diagnostic, or clinical is quite important in these instances, and the main ethical issues are things like whether prenatal screening or abortion are justified, etc.

Ethical issues abound, however, in the case of most traits, where genotypes are only vaguely known or have weak predictive power. There the question is what the relationship between a known genotype and actual risk is, and at what level of risk something should be done about it. Or whether, if nothing can be done about it, it is useful to worry people.

Who gets to see the information in either case is important. Can or should it be used to force treatment or preventive measures on people as a condition of insurability? Or to adjust health insurance premiums? Or to screen relatives? Or decide about employability?

Weak predictive power often means such incomplete knowledge that the genotype may not, in fact, make reliable or replicable effect on risk. The problem here, which we are already beginning to see, is that genotyping leads people to confront their physicians with diagnoses that the physician may or may not agree with (or understand, since much of this area is quite complex), but may feel obliged to do something about.

In a country in which the health care system is already overburdened, and will become even more so as the population ages, personalized genotyping can lead to large-scale over-diagnosis, new and unnecessary testing, and lifelong costly maintenance such as multiple screening checkups, preventive medication, and so on. Much in the way of profit to the system, much in the way of distraction for lawyer-wary doctors, but not much in the way of additional health. Indeed, overdiagnosis leads to overtreatment and hence actual increase in risk.

These and other issues, like the value (or not) of 'racial profiling' in medicine, were discussed at this meeting. There aren't answers, exactly, but at least the issues are being raised. Whether the issues are being examined deeply enough -- for example, as to ask whether some of these activities should be legal, or how much research money should be invested (or wasted, depending on your viewpoint), get less discussion, because our system places vested interests across the spectrum of people from commercial to academic to clinical.

Certainly, as everyone agreed, the genomics perspective is here to stay at least for a while. Probably, much of the promise and hype will prove to be false and will simply fade away. What is discovered that is useful will become part of standard practice and a source of better diagnosis and treatment. It is usual that most of what people claim at this or any time proves to be rather worthless. That's likely to be the same in this instance. But, as is also usual, some gains are made and they set the stage for the next wave of ideas about how genes work and how health can be improved.

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