Unzipping Ethical Dilemmas regarding Parental Authority in Prenatal Gene Therapy

While targeted gene therapy in adult and pediatric patients has gained momentum in oncology and rare inherited diseases, parental pursuit of in utero gene therapy (IUGT) is more fraught. IUGT seeks to maximize therapeutic intervention to the fetus at minimal risk to the pregnant person, but few models exist to delineate the ethical distinctions between the two patients, and there are many as-yet unexplored nuances regarding therapeutic strategies, timing of interventions, and possible ramifications. Additionally, while parental authority is widely invoked in the pediatric ethics literature, the content, strength, and scope of this concept are vigorously disputed. To date no models specifically address parental decision making for IUGT, due in large part to its novelty and its limited use in research settings. However, as gene and cell therapy have advanced rapidly to regulatory approvals, the same is likely for IUGT, prompting our exploration of how best to understand and evaluate factors such as illness severity, onset of symptoms, and weighing treatment risks against therapeutic benefits. This panel will introduce and debate the merits of a gradient model of parental authority as a comprehensive tool for ethical decision making regarding IUGT, with greater decisional authority afforded for more devastating diseases with easily targetable genetic mutations, and stricter limits to parental authority applied to mild disease states with difficult genetic target sites. This ethical model will be explored from multiple professional perspectives, including clinical genetics, industry R&D, genetic counseling, and philosophy, and applied to multiple clinical scenarios where IUGT is being considered.