Table 6.

Previously proposed risk assessment and monitoring challenges associated with the deliberate release of gene drive modified organisms into the environment

Related to	Previously proposed risk assessment and monitoring challengesa
Engineered gene drive system	Prediction of all relevant genomic effects that could emerge in the next and subsequent generations, and from interactions with the receiving environments Evaluation of off‐target changes and their consequences over time in different genetic backgrounds and their potential accumulation in populations The potential for the engineered gene drive to evolve after release, including through unexpected genetic drift Controllability of engineered gene drive systems after release
Target organism	Need for information on the potential genetic diversity of the target species Need for information on the functional role of the target organism and potential cross‐compatible species in the various ecosystems that may be encountered Consideration of the reproductive strategies, population dynamics and life cycle of the target organism Consideration of possible evolution of resistance in pathogens regarding disease vector control
Receiving environment	Need for information on the potential for hybridisation with non‐target organisms Diversity of potential receiving environments, and limited information on the potential interactions with natural receiving environments Limited information on long‐term evolutionary processes occurring in ecosystems
Risk assessment methodologies	Difficulties of applying the stepwise approach for risk assessment Challenges to the comparative risk assessment framework Assessing and taking into consideration uncertainty Need to address the broader temporal and spatial scale Higher dependency on model‐based predictions (e.g. to address the long temporal and wide spatial scale of some engineered gene drive applications and to anticipate the range of scenarios for the possible evolution of the engineered gene drive in the environment) Difficulty to predict the non‐linear, exponential effects of engineered gene drives Difficulties in assessing next generation effects of organisms containing engineered gene drives The need to develop knowledge and procedures for assessing the engineered gene‐drive's long‐term effects on ecosystems Difficulty to comprehensively assess risks prior to release
Data collection and analysis	Additional information needed on the molecular characterisation of both the engineered gene drive mechanism and the engineered gene drive‐bearing organism Information to predict off‐target effects and potential consequences in the target organism Advances in conceptual approaches are required to understanding the novel evolutionary and ecological couplings and feedbacks that gene drive modified organisms generate Lack of environmental and ecological data Difficulties with obtaining data for relevant modelling Difficulties with validation and calibration of modelling data before the occurrence of an environmental release
Risk mitigation and monitoring	Challenges pertaining to post‐release environmental monitoring Evaluation of impacts over long periods of time Need for monitoring plans at supranational level to follow the spread of the engineered gene drive Proven strategies for controlling the spread of an engineered gene drive, should monitoring data show that it has adverse effects on human, animal and plant health or the environment Unavailability of management plans for possible reversion

^aBased on NASEM (2016), CSS–ENSSER–VDW (2019), ATHEG (2020), Dolezel et al. (2020a,b) and Then et al. (2020).