A plenary debate, entitled “Current and Emerging Sequencing Technologies: Changing the Practice of Medical Genetics,” provoked strong and divergent opinions at the combined American Society of Human Genetics (ASHG) and International Congress of Human Genetics (ICHG) conference held recently in Montreal.
Han Brunner, M.D., Ph.D., a clinical geneticist and professor of human genetics at University Hospital and Radboud University, moderated the debate, which in the end generated more questions than answers, highlighting the strong opinions and emotions surrounding the role of genome sequencing in medicine today and into the future.
The panelists represented a range of viewpoints, expressing the perspectives of industry, researchers, clinicians, and patient advocates. They included Joris Veltman, Ph.D., associate professor, department of human genetics, Radboud University; Radoje Drmanac, Ph.D., co-founder and CSO at Complete Genomics, Ségolène Aymé, a medical geneticist and epidemiologist, director of research at INSERM and coordinator of the Orphanet platform for rare disease registries; Louanne Hudgins, M.D., professor and chief, division of medical genetics in the department of pediatrics at Stanford University School of Medicine; Michael Hayden, Ph.D., director and senior scientist, Centre for Molecular Medicine and Therapeutics, and University Killam professor, department of medical genetics, University of British Columbia; and Ming Qi, Ph.D., director and professor, Zhejiang University Center for Genetic and Genomic Medicine, China.
The panelists each had an opportunity to respond to four statements, and then to discuss and debate each others’ responses: 1) Targeted sequencing will remain the norm for diagnostic medical genetics because whole exome and whole-genome sequencing (WGS) will yield an excess of information that is useless, counterproductive, and possibly damaging to the patient. 2) Personal genome sequencing creates an unacceptable risk to the privacy of people. 3) Cytogenetics will cease to be. Sequencing is the only future technology in diagnostic labs. 4) Personal genomes will be incorporated in the standard of care for all medicine. Therefore, medical genetics will disappear as a separate medical specialty.
Han Brunner summed up the main challenge implicit in all of these statements, asking the panelists, “How do we take this beast of a new technology and use it for the advantage of our patients?” And that, above all else—how to use WGS to improve human health—was the facet on which the panelists could all agree, that ultimately, the use of next-generation sequencing (NGS) technology in clinical medicine had to benefit patients and their families.
Notwithstanding that the ability to do targeted DNA sequencing, exome sequencing, or whole-genome sequencing accurately and cost effectively is a remarkable scientific achievement and is here today, or that the data generated has incalculable value from a scientific and research perspective, are we ready to share this information with clinicians and patients, do we really know what it means in terms of predicting inherited disease risk, diagnosing disease predisposition, providing reproductive counseling, or managing disease, and do we know how to interpret and apply sequence information to impact prognosis, treatment, or quality of life?
The areas of consensus were quite clear, the points of disagreement less so, as the panelists debated: whether genome sequencing technology should be implemented simply because it is available; whether it is immoral not to gather the most information you possibly can about a patient’s disease; who “owns” and has a responsibility to store, protect, and reanalyze individuals’ genomic data; what do patients want to know; and where is the line (and how do you keep it from blurring) between clinical research and clinical medicine and when is it appropriate to cross the line from applying NGS information for scientific discovery to using it to guide clinical decision making; and how do we maintain a clear distinction between disease-related sequencing and screening, and should clinicians handle incidental findings.