Ethical implications of new genetic technologies

Field: Medicine (Health Sciences)

The speed by which a person's genome can be analysed has increased phenomenally over the last few years, while the attendant costs have declined rapidly. Although the $1000 genome is not yet routinely available, if the pace continues, it soon will be. This has the potential to not only to transform the clinician's diagnostic and predictive ability, but clinical management will also be affected: preventative therapies, surveillance regimes, or treatments personalized according to genetic make-up mean that more people are likely to want to know about their genetic predispositions. Until recently, genetic diagnoses were often equivalent to the search for the needle in the haystack, and once found, at best offered only reproductive choices. This situation has changed over the last decade, and is beginning to impact on most all areas of medicine, and there are calls to prepare for this rapid transformation in practice.1 Any technological advance brings new challenges. The ethical and legal aspects of managing this enormous volume of person-specific biological data are not unique to genetics but there are nuances that merit consideration. A widespread perception that genetic tests deliver certainty has to be matched with the complexity of multifactorial aetiologies of disease. Whilst the technology can deliver, the interpretation of the data, in order to accurately predict clinical risk, lags behind. There are dangers of oversimplification; 'having a gene' for a condition, when in fact the increase (or decrease) in risk of the condition is subtle, or only exists in the presence of another variant or group variants, perhaps in turn in combination with environmental exposures during fetal or adult life. Research is delivering fast here; multiple risk factors have been identified and have provided important insights into disease mechanisms, but at the same time their predictive powers are not always as good as anticipated. For example, a recent study of more than 100 variants associated with coronary heart disease had no better predictive powers than taking a detailed family history.2 Interpreting the output of exomes or genomes with millions or billions of basepairs requires complex bioinformatic analysis, skills still to be acquired by sufficiently large numbers in order to keep pace with the demand. Shifting from the traditional focused 'fishing' of the genetic code (looking for particular variants suggested by clinical signs or symptoms) to 'trawling' the code (looking for any variant) will provide more 'fish' at lower cost, but will also discover 'junk' of little value or perhaps more dangerous items such as unexploded bombs. Trawling of the genetic code is in itself not new; a karyotype analysis of chromosomes could find completely unexpected abnormalities, but the level of resolution meant that such events were relatively rare. Exome and genome outputs will change this. One technique, comparative genome hybridization (aCGH), has already entered clinical practice and detects genomic imbalances on a much higher resolution than its precursor tests. It is not unusual to find genetic code anomalies that are completely unrelated to the presenting clinical features. Some will be of dubious or uncertain clinical significance, but others will predict a high chance of disease at some point in the future. Whilst findings that have clinical relevance now will usually require some sort of clinical management, and findings of uncertain significance can be reinterpreted as evidence accumulates, a fairly certain prediction of future disease, is a relatively new challenge arising from these new technologies. On the whole, research has dealt with this challenge by declaring up front that such incidental findings would not be disclosed (although this is beginning to be challenged),3 though this is harder in clinical practice. For example, a 4-year-old investigated for developmental delay is found to have a deletion of a tumour suppressor gene, which predicts if he will develop bowel polyps in about 10 years time, leading to cancer a decade later. Regular surveillance can modify the disease course, but not until early adolescence, and the finding is not apparently related to the symptoms that his parents have asked to be investigated. As such findings become more likely, we will need to develop the skills to deal with them adequately during consent to genetic investigations, as well as to communicate findings appropriately. Making a genetic diagnosis in one person can have implications for their relatives; results from one person may indicate others who might benefit from testing. We will need to develop acceptable mechanisms of disseminating such information to ensure that preventative options are not missed yet patients can still trust their health professionals to keep their medical confidences.4