Microarrays have now entered the realm of clinical diagnostics for a number of applications, including prenatal genetic testing. In this article, we focus on ethical issues in the application of microarrays to the study of complex traits, an area of increasing research that is only in the earliest stages of potential clinical application. Because complex traits are often more prevalent in the population than Mendelian traits, the use of microarrays for diagnostic purposes has much broader ethical and societal implications.
As with the advent of many new diagnostic technologies in medicine, the use of microarrays has provided unprecedented power to detect biochemical, morphological, and physiological differences, sometimes of unknown or unconfirmed clinical significance. This power also creates challenges that have important ethical implications that should be considered. Many of the ethical issues raised by microarrays are not new. For example, clinical geneticists and genetic counselors have extensive experience thinking and communicating about ethical issues with their patients, and many of the issues in microarrays parallel issues involved with other genetic diagnostic techniques. Furthermore, many of the ethical issues involved with the application of microarray technologies exist broadly for many new diagnostic technologies.
The use of microarrays raises at least four issues that exist broadly for many new diagnostic technologies. Although the ethical issues in microarray application to complex traits may not all be novel, we suggest that these issues merit consideration and reexamination in this context. First, do we understand normal variation enough to know what is “abnormal” or “pathogenic”? If not, use of the tests could cause more harm than good to patients and their families because of the probability that they provide inaccurate information that may lead to unnecessary anxiety, clinical procedures, or even termination of pregnancy.1
Second, because new technologies like microarrays allow inferences to be made about traits that are not necessarily associated with morbidity or mortality, or traits that are nonmedical (such as personality or hair color), there is concern that the availability of the technology may increase pressure on prospective parents and clinicians to screen for “imperfections” to eliminate them.2
Such screening raises the specter of eugenics3
and raises questions about the appropriate role of the clinician in providing information that is not about health and disease.
Third, new powerful technologies, like the comprehensive and detailed analysis of the genome afforded by microarray analysis, creates a greater potential for incidental findings. Incidental findings are those that are identified by the application of a new technology that were not part of the original scope of what was being examined. This is a common theme of new diagnostic technologies: their ever-increasing ability to observe phenomena before the clinical significance is known. For example, radiologists are increasingly encountering unidentified bright objects, or UBOs, in magnetic resonance images (MRI) of the brain. A study of MRI scans of healthy children found 13% with “abnormalities.” However, on follow-up examination and after re-scanning 24 months later, none of these UBOs was found to be of clinical significance.4
In addition, the rates of incidental findings in neuroimaging vary widely, including reports of 20% of scans with incidental findings among asymptomatic individuals5
or even 40% among research participants.6
However, much lower rates of findings with clinical significance suggest the possibility of high false-positive rates.7
Results like these suggest that applying these new diagnostic tools in a clinical context prematurely may be unethical because it increases the potential for harm to patients, either because of over-treatment, under-treatment, unwarranted labeling and stigmatization, or a false sense of security.
Fourth, despite our current lack of a comprehensive understanding of the implications of microarray analysis, the large number of loci analyzed will create an unprecedented volume of information for patients, counselors, and health care providers. This makes it very challenging to envision what adequate informed consent means and how to achieve it.
It is important to reiterate that these issues are not new to medical geneticists or genetic counselors. However, they do raise issues for consideration by researchers who are using the technology, especially in the examination of complex traits, because of the implications of the findings for later clinical application and translation of the technology.