Synthetic gene drive: between continuity and novelty: Crucial differences between gene drive and genetically modified organisms require an adapted risk assessment for their use

CRISPR/Cas accelerates the development of synthetic gene drive organisms to quickly spread a genetic modification among the target species. Both in academia and politics, the use of CRISPR/Cas gene drive to potentially control disease vectors, plant pests or invasive alien species is controversial, as exemplified by the last Conference of the Parties of the United Nations Convention on Biodiversity (CBD) and the most recent meeting of its scientific expert group on synthetic biology (Ad Hoc Technical Expert Group/AHTEG). While some argue that current risk assessment frameworks can accommodate synthetic gene drives, others call for a moratorium owing to gene drives’ potentially detrimental impact on wildlife. In essence, the question is whether we have sufficient experience and knowledge to handle this technology safely. Experience and knowledge in turn depend on the degree of continuity and novelty of synthetic gene drive organisms (GDO), compared to existing genetically modified organisms (GMO). While gene drives exist in nature, we find that GDO differ from the currently released GMO on five levels. A clear understanding and analysis of these differences is crucial for any risk assessment regime and a socially acceptable and ethical evaluation that is vital for the application of this technology. ### From nature to synthetic biology Gene drive is a natural phenomenon by which a genetic element is transferred to more than 50% of the offspring of a sexually reproducing organism: natural gene drives are selfish genetic elements that sidestep the rules of Mendelian inheritance, resulting in a so‐called super‐Mendelian inheritance. In 2003, Austin Burt proposed to use this natural phenomenon and synthetically engineer gene drives using specific enzymes called “homing endonucleases.” The discovery of the natural bacterial defence system CRISPR/Cas and its application as a highly specific nuclease eventually boosted the development of synthetic gene drives to circumvent Mendelian inheritance of both the gene drive elements itself …