Spatiotemporal Controllability and Environmental Risk Assessment of Genetically Engineered Gene Drive Organisms from the Perspective of European Union Genetically Modified Organism Regulation

Abstract

Gene drive organisms are a recent development created by using methods of genetic engineering; they inherit genetic constructs that are passed on to future generations with a higher probability than with Mendelian inheritance. There are some specific challenges inherent to the environmental risk assessment (ERA) of genetically engineered (GE) gene drive organisms because subsequent generations of these GE organisms might show effects that were not observed or intended in the former generations. Unintended effects can emerge from interaction of the gene drive construct with the heterogeneous genetic background of natural populations and/or be triggered by changing environmental conditions. This is especially relevant in the case of gene drives with invasive characteristics and typically takes dozens of generations to render the desired effect. Under these circumstances, “next generation effects” can substantially increase the spatial and temporal complexity associated with a high level of uncertainty in ERA. To deal with these problems, we suggest the introduction of a new additional step in the ERA of GE gene drive organisms that takes 3 criteria into account: the biology of the target organisms, their naturally occurring interactions with the environment (biotic and abiotic), and their intended biological characteristics introduced by genetic engineering. These 3 criteria are merged to form an additional step in ERA, combining specific “knowns” and integrating areas of “known unknowns” and uncertainties, with the aim of assessing the spatiotemporal controllability of GE gene drive organisms. The establishment of assessing spatiotemporal controllability can be used to define so‐called “cut‐off criteria” in the risk analysis of GE gene drive organisms: If it is likely that GE gene drive organisms escape spatiotemporal controllability, the risk assessment cannot be sufficiently reliable because it is not conclusive. Under such circumstances, the environmental release of the GE gene drive organisms would not be compatible with the precautionary principle (PP). Integr Environ Assess Manag 2020;16:555–568. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Outcome of the public consultation on the draft Scientific Opinion on the evaluation of existing guidelines for their adequacy for the molecular characterisation and environmental risk assessment of genetically modified plants obtained through synthetic biology

“…In addition, all relevant genomic data providing information on the exact genetic changes should be collected and made publicly available in data bases, amongst others, to allow independent research. Finally, cut-off criteria will be needed to take decisions on the conclusiveness of risk assessment in the face of major uncertainties (see Then et al, 2020b Plants engineered using SynBio approaches are more likely to include complex traits controlled by multiple genes and/or multiple changes to the plant by either inserting numerous transgenes, or by deleting or editing multiple endogenous genes. The phenotypes may therefore be more complicated to assess than those considered in the case studies (e.g.…”

“…In this case, measures to prevent uncontrolled spread must be put in place. In addition, cut-off criteria will be needed to make decisions on the conclusiveness of risk assessment in the face of major uncertainties (see Then et al, 2020b Comment RIVM: We refer to our earlier comment for 3.1.5 Bioinformatic analyses. We stated in that section that the probability of HGT only needs to be determined on a case-by-case basis e.g.…”

“…At this stage it would be too early to enter a detailed discussion on what can efficiently assessed in a prospective risk assessment and in post market monitoring. Therefore, we propose to keep this point in the opinion (see also comment 169) Therefore, cut-off criteria will be needed to take decisions on the conclusiveness of risk assessment in the face of major uncertainties (Bauer-Panskus et al, 2020a, Then et al, 2020b, because such uncertainties cannot be subjected to monitoring as foreseen in EU Regulation.…”

“…In addition, cut-off criteria will be needed to make decisions about the conclusiveness of risk assessment in the face of major uncertainties (see Then et al, 2020b).…”

Outcome of the public consultation on the draft Scientific Opinion on the evaluation of existing guidelines for their adequacy for the microbial characterisation and environmental risk assessment of micro‐organisms obtained through synthetic biology

“…Also EFSA, in its draft document, states that in many cases, available information and risk assessment methodology will not be able to "fully predict the capability of a synthetic organism to survive, colonise and interact with other organisms under natural conditions, given the uncountable diversity of potential microhabitats and their temporal variability." Against this background, EFSA should introduce a set of cut-off criteria which will allow decisions to be made on the conclusiveness of risk assessment (see Then et al, 2020). If risk assessment is identified as inconclusive, no release can be permitted because it would not be compatible with the precautionary principle.…”