Investigating the (un)acceptability of human germline gene editing: engaging the public and exploring worldview-based perspectives

Human genome editing is advancing rapidly. CRISPR-Cas9, discovered in 2012, has transformed the field. Somatic gene editing (SGE) is moving toward clinical use, but human germline gene editing (HGGE) remains largely prohibited. Because HGGE could affect all of humanity, it raises ethical and societal questions that cannot be addressed by scientists alone. This thesis maps and evaluates whether and how public engagement regarding HGGE has been conducted in practice (Part I) and examines worldview-based values shaping perspectives regarding HGGE to inform dialogue and policymaking (Part II). Part I: Reflection on public engagement regarding human germline gene editing Chapter 2 presents a systematic scoping review of public engagement studies on HGGE (2012–2023), assessed through three points of attention: inclusion of underrepresented groups, reported outputs (values versus acceptance), and reported objectives regarding societal impact. A systematic literature search identified 3464 records; after screening, 36 articles remained, covering 31 engagement studies. We conclude that co-created efforts are needed to better include underrepresented groups, to elicit values rather than acceptance levels, and to clarify how engagement could lead to impact. Chapter 3 provides directions for broad and inclusive public and stakeholder engagement (PSE) by emphasizing futures literacy: the skill to imagine multiple futures and use these as lenses to view the present anew. Starting with “what if” questions can broaden conversations before moving to “whether” or “how” questions about HGGE. Chapter 4 outlines the goals of our Dutch project De DNA dialogen (The DNA dialogues). We argue that setting explicit goals in advance is essential for meaningful PSE and evaluation. Our goals are to deliberate on “what if” questions, map agreement and disagreement in values and beliefs, involve diverse publics with attention to those typically underrepresented, and support societally aligned policymaking by conveying how values are weighed in relation to democratic rule of law and fundamental rights. Part II: Worldview-based perspectives regarding the (un)acceptability of human germline gene editing Chapter 5 explored views of carriers of autosomal dominant disorders on SGE and heritable genome editing (HGE) and the role of secular or religious worldviews. Ten interviews were analyzed using reflexive thematic analysis. Participants balanced a desire to prevent serious disease through HGE with fear of harmful impact on society and nature. They were positive toward safe SGE, and most supported HGE only to prevent severe conditions; a few opposed HGE in any case based on religious beliefs. Overall, perspectives were often ambivalent, indicating that engagement should make space for weighing values. Chapter 6 reports interviews with religious Dutch midwife counselors about worldview in counselling for prenatal anomaly screening and perspectives on HGE. Counselors described tensions between professional norms and worldview-based values, and concerns about slippery slopes around treatment versus enhancement, severity assessments, and societal views on disability and quality of life. Chapter 7 presents interviews with Dutch Christian faith leaders (2019 and 2024) about values, pastoral counselling, and legislation regarding HGGE. Views were underpinned by human dignity, humility, alleviation of suffering, acceptance, compassion, and justice. Participants described offering unconditional support in counselling while reflecting on motivations, and called for great caution and restrictions against enhancement. Concluding remarks Despite repeated global calls for public engagement on HGGE, actual engagement efforts remain limited. Our work suggests that explicit exploration of worldview-based values and genuinely co-created approaches to include underrepresented groups are needed to better align policymaking with what people find important. Stakeholders expressed cautious support for HGGE limited to very serious conditions, alongside concerns about societal consequences. As the technology advances, more co-created, value-focused, transdisciplinary engagement is needed so that policy decisions reflect public values, not only safety and efficacy.