FEATURE
Ethics and Challenges of Delivering
Genomic Medicine
Michael Szego, PhD, MHSc Clinical Ethicist, Centre for Clinical Ethics (A joint venture of Providence Healthcare, St. Joseph’s Health Centre, and St. Michael’s Hospital), The University of Toronto Joint Centre for Bioethics Research Ethics Consultant, The Centre for Applied Genomics, The Hospital for Sick Children, The University of Toronto McLaughlin Centre for Molecular Medicine
I
n 2000, one of the most significant milestones in genomics was achieved: the first draft of the human genome was completed1. The genomic sequence was based on DNA samples pooled from several individuals and it established a reference genome for future sequencing projects. At the press conference announcing this achievement, Bill Clinton proclaimed that the completed genome sequence would “revolutionize the diagnosis, prevention and treatment of most, if not all, human disease”2. Francis Collins, who led the effort to complete the human genome project, may have been try-
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Since 2000, whole genome sequencing (WGS) of individual genomes has been developed, enabling the identification of new gene variants associated with disease that can subsequently be used for genetic testing in the clinical context3. The WGS is still cost prohibitive with its use and is limited to select research projects; however, its cost is decreasing rapidly and will soon be cheaper than currently employed genetic tests that assess one gene at a time. The development of affordable WGS may be the catalyst for the transformation that Dr. Collins predicted and the “revolution” that Clinton anticipated. Since WGS has the potential to unlock every person’s unique disease risk profile4, it may be one of the most significant technological breakthroughs in history. Therefore, WGS deserves special consideration from an ethics perspective. In this short article, I will focus on two key ethical topics with respect to WGS that are found in both research and clinical settings, that is (1) informed consent and, (2) return of results.
Informed consent The principle of informed consent is recognized as a main pillar in the practice of ethical research and medicine. For consent to be informed within the general research context, the research subject must be informed of the purpose for the research, its potential applications, the methods that will be employed, and any anticipated benefits and risks5,6. However, many of these criteria are
unrealistic when applied to genomic research specifically. At the time a DNA sample is taken from the research subject, all possible future research, its applications, and methods are usually not known. One main risk/benefit associated with most genomic research projects is the potential identification of incidental findings. For instance, the disclosure of a pathogenic variant that is clinically actionable which is identified over the course of research is an example of a potential benefit, while possible genetic discrimination is an example of a potential risk. However, the actual risks and benefits are not known beforehand because they depend on the research subject’s genomic sequence and the scientific knowledge at the time the analysis. In order for genomic research to be performed, the traditional informed consent process has been modified to include broad consent. In the broad consent model, participants consent to a range of possible research activities7. Under this paradigm, research subjects are educated about genomic research to ensure they understand the general risks and benefits. Consequently, they can make the most informed decision possible, even though the actual risks may not be completely known. Informed consent is a different process within clinical medicine as compared to research. In the clinical genetic testing context, patients must be told the nature of the diagnostic test, the expected risks and benefits of the test, and any alternative tests for consent to be informed. When WGS is used as a clinical genetic test, the nature of the diagnostic test and any alternative tests are known and can be described to the patient. Current standards of care for clinical genetic testing include patient counseling about the risks and benefits and potential outcomes of the proposed genetic test. However, current genetic tests can examine one or a handful of genes, making counseling more straightforward than coun-
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ing to manage expectations when he suggested that a complete transformation of therapeutic medicine would take up to 15 to 20 years2. One of the biggest hurdles that needed to be overcome before Clinton’s claims could be realized was the ability to sequence individual genomes. This feat required technological advances in sequencing and a drastic reduction in sequencing costs.