Page - 108 - in Critical Issues in Science, Technology and Society Studies - Conference Proceedings of the 17th STS Conference Graz 2018

• analysis/assessment of opportunities for shaping science and technology and technical or socio-technical alternatives • reflection on normative issues, values and interests involved. In the following, I will address several of these aspects in order to demonstrate the need for such exercises of technology assessment. Potentials and development risks We have already seen laboratory experiments with relevant mosquito species based on gene drives constructions using CRISPR-Cas9. Up to now four gene drive constructs have been engineered in the lab: one in the fruit fly Drosophila melanogaster (Gantz/Bier 2015), one in yeast (DiCarlo et al. 2015), two in mosquitos (Gantz et al. 2015, Hammond et al. 2016), which transmit malaria (Anopheles stephensi, Anopheles gambiae). However, it turned out that after several mosquito generations the chain reaction slowed down in most of the cases, the engineered gene drives became unstable. Thus, a potential, which could be exploited in principle, has been made visible, but not more. What has been achieved scientifically are steps towards a theoretical proof of concept in the laboratory. In general, two main development paths of gene drives which are relevant for combatting malaria vectors are envisioned: • suppression drives aim at dramatically reduce malaria transmitting mosquito populations regionally or globally – probably eradicate them • modification/manipulation drives strive to manipulate mosquitos (or probably the pathogen) so that malaria infection of humans is reduced or disabled. The principle potential of gene drives is seen as advantageous by the scientists involved in R&D. They believe that the efficacy of gene drive strategies could be much more target specific with much lower “collateral damages” than for other technological approaches currently in use. However, first of all, it is unclear so far whether gene drives in mosquito wild populations will be feasible: • The observed slow down of gene drives can be partly explained with the occurrence of resistance against the gene drive construct (Unckless et al. 2017, Champer et al. 2017). The mechanism can be roughly explained as follows. CRISPR-Cas9 finds appropriate locations of the mosquito´s DNA by specifically designed short guide-RNA strains. At these sites a cleavage of the DNA is induced and specifically designed “homing endonuclease genes” are copied into these cleavage sites thereby creating a construct which is inherited at a super Mendelian rate if copied into the germ line. Prerequisite for that result is that a repair mechanism for the DNA is working in a suitable manner. This wanted repair mechanism is called Homology Directed Repair (HDR). But there is a competing repair mechanism called Non Homologous End Joining (NHEJ). If the repair is done by NHEJ the target site cannot be recognized anymore by the gene drive. Therefore, CRISPR-based gene drives have the propensity to generate resistance alleles which cannot be converted anymore to drive alleles. Eventually the mutagenic chain 108