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ETHICAL ISSUES AT THE INTERSECTION OF IMAGING AND GENOMICS JUDY ILLES, PH.D., SENIOR RESEARCH SCHOLAR STANFORD CENTER FOR BIOMEDICAL ETHICS AND DEPARTMENT OF RADIOLOGY, STANFORD UNIVERSITY INTRODUCTION Consideration of the ethical challenges introduced by advanced capabilities in medical imaging has been identified as a key priority for the new discipline of neuroethics [1-3]. Although debate about brain, mind and behavior dates well back to the ancient philosophers, neuroethics in its broadest modern definition embodies the examination of theoretical and practical issues in the neurological sciences that have moral and social consequence in the laboratory, in health care, and in the public domain. At many levels, the challenges faced by the new discipline have already been confronted in genomics [4,5]; where these challenges intersect and where they diverge with respect to biomedical imaging and brain function specifically is the focus of the discussion here. EMERGING TRENDS IN IMAGING BRAIN FUNCTION AND BEHAVIOR In a recent report, Illes et al. [6] provided empirical validation of the expanding terrain of brain imaging studies using functional magnetic resonance imaging (fMRI). FMRI is a powerful new imaging tool based on noninvasive measures of cerebral blood oxygenation during task-related activity, and has had a particularly significant impact on the imaging neurosciences given its wide availability and unprecedented coupling of spatial resolution and safety. Through an analysis of the more than 3400 peer-reviewed papers examining the application of fMRI, alone or in combination with other neuroimaging modalities in the decade between 1991 (the genesis of fMRI) and 2001, a steady growth in studies with evident social and policy implications was demonstrated. These included studies of human cooperation and competition, brain differences in violent people, judgments about race, genetic influences, and variability in patterns of brain development. As fMRI continues to mature today and ongoing research seeks to define its methodological scope and limits, outstanding issues about individual reliability of such findings and their diagnostic and predictive validity for real-world behaviors, especially those that are potentially value-laden or culturallydetermined, are becoming steadily addressed. Nonetheless, there is already growing regard for the novelty and breadth of information that neuroimaging can deliver about the complexity of human behavior – a scientific and popular acceptance that provides a compelling need for critical thinking about the related ethical issues. To ensure that the enthusiasm for and benefits of such new information outweigh associated risks in any of the areas in which neuroimages may play a practical role, this thinking needs to harness knowledge from lessons learned in the past, and leverage multidisciplinary perspectives of all stakeholders – neuroscientists, scholars in the humanities and law, bioethicists, journalists, patients, consumers and others. A FRAMEWORK FOR CRITICAL THINKING ABOUT ETHICAL ISSUES IN IMAGING In this early phase in the life of imaging and ethics inquiry, a first step towards the development of a framework for critical ethical thinking in the discipline is identification of key issues. We have begun to structure our own thinking to achieve this goal according to three domains: advancement of science and basic knowledge about the human condition, translation in clinical medicine, and translation outside health care. Issues that have already come to the foreground are as follows: Advancement of science and basic knowledge: In this first domain, the prima facie question of moral and social acceptability of neuroimaging research topics and study design immediately intersect with similar questions posed for genomics. We must ask, for example, whether all studies of normative neurobehavioral phenomena are ethically acceptable. How might social or racial biases affect applications of the technology, the conditions under which scans are performed, or the way interpretations are made? By contrast, specific to neuroimaging, are questions such as what a statistically normal activation pattern of moral behavior really means. Extending this theme, what would the implications of an abnormal brain activation pattern be in a study of healthy subjects performing a task that involves moral reasoning, deception or sexual responsiveness? Dilemmas posed by incidental findings of structural anomalies in medical research have been raised in the past and have surfaced recently for research MR scans specifically [7,8], but incidental findings of functional anomalies may give rise to an entirely other kind of challenge related both to the interpretation and appropriate use of data. Ensuing questions relate to whether such findings should be communicated to a participant. Here it is imperative that we return to genomics and other areas of biomedical research and consider what a participant would want to know, and what are the risks of inadvertent disclosure or exploitive use of such information. Translation in clinical medicine: With sharp increases in numbers of fMRI studies with clinical applications demonstrated in the Illes et al. [6] database, and more than 50% of review articles devoted to clinical issues, the imperative for translating advancements in basic research to clinical neurological environment is evident. But, akin to genetic testing, what moral reasoning will be needed to determine the trade-offs of risk and benefit of such complex new information – a visual activation image – for a patient diagnosed, for example, with a major depressive disorder? What impact might quantitative “hard” evidence provided by a brain image have on a patient’s understanding about his or her own disorder? What are the risks of a scan that is nondiagnostic and therefore disconcordant with results obtained using qualitative gold standards? What are the risks of medicalizing behaviors that have been previously considered antisocial but not pathologic? The issues for predictive imaging are no less trivial. Well known to genetics is the ethical quandary of diagnosing a disease, such as Alzheimer’s, for which there is no cure. But how we will manage brain activation information that might predict a propensity for violent behavior? Guidelines are needed to ensure that such data are utilized for the benefit of early intervention while the risks of misuse in profiling or stigmatization are averted. At the heart of the issues is who will have access to intervention programs, who will pay and, as with genetic information, what is the duty to inform third parties. Similar moral quandaries arise as the emergence of self-referred body scanning in the open consumer marketplace may lead to real prospects for self-referred neuroimaging to justify or predict, for example, remedial training or enrichment for children in the educational setting. Might advanced new medical capabilities such as those afforded by diagnostic prenatal MR imaging even become adopted for predictive screening for complex behavioral traits? Translation outside health care: In an era of increasing violence in our society and increasingly powerful imaging capabilities for detecting neurobehavioral phenomena such as lying and deception, the implications for responsible application of the technology in the criminal justice system quickly surface. With the predilection for juries to put great credence into expert testimony and evidence [9], appropriate dismantling of information available from visual activation images is critical to the appropriate communication of the information they provide. In parallel, and as the ubiquity of neuroimaging technology such as fMRI becomes even further realized, screening in airports and schools may become a real possibility. Who will be screened, who will interpret the data, and how the data will be used are but a few of the challenges familiar from genomics with which we will be faced. SUMMARY COMMENTS One of most profound lessons we have learned from the past is that whether we are dealing with biological facts, as in genetics, or computational estimates, as in neuroimaging, the expression of behavior is a function not only of the physiologic predisposition of an individual, but the individual’s complex social and emotional whole. Once critical ethical issues are identified, a further framework for a responsible approach to addressing them will evolve through broad acceptance of the issues, a common language for engaging in dialogue about them, and precedent- and evidence-based process and consensus. If we are to engage in such a new form of “neurodeterminism,” whatever shape it may take, it behooves us to think proactively about how we will adjudicate between outcomes determined by behavioral genetics, those that are self-fulfilling and those that are a combination of both, and the impact on our society at large. [1] Marcus SJ. (ed.) Neuroethics: Mapping the Field Conference Proceedings, The Dana Foundation, New York, 2002. [2] Illes J, Raffin TA. Neuroethics: An emerging new discipline in the study of brain and cognition. Brain and Cognition. 2002;50(3):341-344. [3] Moreno J. Neuroethics: An agenda for neuroscience and society. Nature Reviews Neuroscience. 2003;(4):149-153. [4] Carson RA, Rothstein MA. Behavioral Genetics, 1999, Johns Hopkins University Press, Baltimore, MD. [5] World Health, Organization, Genomics and World Health. Report of the Advisory Committee on Health Research, Geneva, 2002. [6] Illes J, Kirschen M, Gabrieli JDE. From neuroimaging to neuroethics. Nature Neuroscience. 2003;6(3):250. [7] Illes J, Desmond J, Huang LF, Raffin TA, Atlas SW. Ethical and practical considerations in managing incidental neurologic findings in fMRI. Brain and Cognition, 2002;50(3):358-365. [8] Kim BS, Illes J, Kaplan T, Reiss A, Atlas SW. Neurologic findings in healthy children on pediatric MRI: Incidence and significance, Amer J Neuroradiol. 2002;(23):1-4. [9] Broyles K. Taking the courtroom into the classroom: A proposal for educating the lay juror in complex cases. George Washington Law Rev. 1996;(64):714, 721-722.