Complexity Meets Risk-The Next Generation of Genome-Edited Plants Challenges Established Concepts for Environmental Risk Assessment in the EU.

For 20 years, the environmental risk assessment (ERA) of genetically modified plants (GMPs) has used a comparative assessment approach, comparing the GMP to presumably safe and familiar non-modified plant varieties. With new genomic techniques, it is now possible to design complex GMP applications with systemic metabolic changes, resulting in novel plant phenotypes. These plant phenotypes can exhibit profoundly altered morphological, physiological, or compositional characteristics, intentionally lacking equivalence with parental plants and non-modified comparators. Through the analysis of case studies involving GMPs with modifications of complex metabolic pathways, we evaluate the current practice of the comparative safety assessment approach applied in ERA in the European Union and its ability to inform ERA, particularly regarding environmental risks. Our findings show that the existing approach has notable weaknesses when applied to complex GMP applications. We suggest complementing ERA with a hypothesis-driven assessment approach that considers various protection goals and relies on whole-plant experimental assessments to draw risk conclusions. As plant modifications become increasingly complex, such as the development of synthetic biology plants, conducting ecologically realistic assessments will be crucial for future ERA.