Horizon scanning of potential environmental applications of terrestrial animals, fish, algae and microorganisms produced by genetic modification, including the use of new genomic techniques.

With scientific progress and the development of new genomic techniques (NGTs), the spectrum of organisms modified for various purposes is rapidly expanding and includes a wide range of taxonomic groups. An improved understanding of which newly developed products may be introduced into the market and released into the environment in the near and more distant future is of particular interest for policymakers, regulatory authorities, and risk assessors. To address this information need, we conducted a horizon scanning (HS) of potential environmental applications in four groups of organisms: terrestrial animals (excluding insects and applications with gene drives), fish, algae and microorganisms. We applied a formal scoping review methodology comprising a structured search of the scientific literature followed by eligibility screening, complemented by a survey of grey literature, and regulatory websites and databases. In all four groups of organisms we identified a broad range of potential applications in stages of basic as well as advanced research, and a limited number of applications which are on, or ready to be placed on, the market. Research on GM animals including fish is focused on farmed animals and primarily targets traits which increase performance, influence reproduction, or convey resistance against diseases. GM algae identified in the HS were all unicellular, with more than half of the articles concerning biofuel production. GM algae applications for use in the environment include biocontrol and bioremediation, which are also the main applications identified for GM microorganisms. From a risk assessor's perspective these potential applications entail a multitude of possible pathways to harm. The current limited level of experience and limited amount of available scientific information could constitute a significant challenge in the near future, for which risk assessors and competent authorities urgently need to prepare.

Challenges for the Post-Market Environmental Monitoring in the European Union Imposed by Novel Applications of Genetically Modified and Genome-Edited Organisms.

Information on the state of the environment is important to achieve the objectives of the European Green Deal, including the EU's Biodiversity Strategy for 2030. The existing regulatory provisions for genetically modified organisms (GMOs) foresee an obligatory post-market environmental monitoring (PMEM) of potential adverse effects upon release into the environment. So far, GMO monitoring activities have focused on genetically modified crops. With the advent of new genomic techniques (NGT), novel GMO applications are being developed and may be released into a range of different, non-agricultural environments with potential implications for ecosystems and biodiversity. This challenges the current monitoring concepts and requires adaptation of existing monitoring programs to meet monitoring requirements. While the incorporation of existing biodiversity monitoring programs into GMO monitoring at the national level is important, additional monitoring activities will also be required. Using case examples, we highlight that monitoring requirements for novel GMO applications differ from those of GM crop plants previously authorized for commercial use in the European Union.

Strategies for Traceability to Prevent Unauthorised GMOs (Including NGTs) in the EU: State of the Art and Possible Alternative Approaches.

The EU's regulatory framework for genetically modified organisms (GMOs) was developed for "classical" transgenic GMOs, yet advancements in so-called "new genomic techniques (NGTs)" have led to implementation challenges regarding detection and identification. As traceability can complement detection and identification strategies, improvements to the existing traceability strategy for GMOs are investigated in this study. Our results are based on a comprehensive analysis of existing traceability systems for globally traded agricultural products, with a focus on soy. Alternative traceability strategies in other sectors were also analysed. One focus was on traceability strategies for products with characteristics for which there are no analytical verification methods. Examples include imports of "conflict minerals" into the EU. The so-called EU Conflict Minerals Regulation requires importers of certain raw materials to carry out due diligence in the supply chain. Due diligence regulations, such as the EU's Conflict Minerals Regulation, can legally oblige companies to take responsibility for certain risks in their supply chains. They can also require the importer to prove the regional origin of imported goods. The insights from those alternative traceability systems are transferred to products that might contain GMOs. When applied to the issue of GMOs, we propose reversing the burden of proof: All companies importing agricultural commodities must endeavour to identify risks of unauthorised GMOs (including NGTs) in their supply chain and, where appropriate, take measures to minimise the risk to raw material imports. The publication concludes that traceability is a means to an end and serves as a prerequisite for due diligence in order to minimise the risk of GMO contamination in supply chains. The exemplary transfer of due diligence to a company in the food industry illustrates the potential benefits of mandatory due diligence, particularly for stakeholders actively managing non-GMO supply chains.

Scanning the Horizon for Environmental Applications of Genetically Modified Viruses Reveals Challenges for Their Environmental Risk Assessment.

The release of novel genetically modified (GM) virus applications into the environment for agricultural, veterinary, and nature-conservation purposes poses a number of significant challenges for risk assessors and regulatory authorities. Continuous efforts to scan the horizon for emerging applications are needed to gain an overview of new GM virus applications. In addition, appropriate approaches for risk assessment and management have to be developed. These approaches need to address pertinent challenges, in particular with regard to the environmental release of GM virus applications with a high probability for transmission and spreading, including transboundary movements and a high potential to result in adverse environmental effects. However, the current preparedness at the EU and international level to assess such GM virus application is limited. This study addresses some of the challenges associated with the current situation, firstly, by conducting a horizon scan to identify emerging GM virus applications with relevance for the environment. Secondly, outstanding issues regarding the environmental risk assessment (ERA) of GM virus applications are identified based on an evaluation of case study examples. Specifically, the limited scientific information available for the ERA of some applications and the lack of detailed and appropriate guidance for ERA are discussed. Furthermore, considerations are provided for future work that is needed to establish adequate risk assessment and management approaches.

Recommendations for the Assessment of Potential Environmental Effects of Genome-Editing Applications in Plants in the EU.

The current initiative of the European Commission (EC) concerning plants produced using certain new genomic techniques, in particular, targeted mutagenesis and cisgenesis, underlines that a high level of protection for human and animal health and the environment needs to be maintained when using such applications. The current EU biosafety regulation framework ensures a high level of protection with a mandatory environmental risk assessment (ERA) of genetically modified (GM) products prior to the authorization of individual GMOs for environmental release or marketing. However, the guidance available from the European Food Safety Authority (EFSA) for conducting such an ERA is not specific enough regarding the techniques under discussion and needs to be further developed to support the policy goals towards ERA, i.e., a case-by-case assessment approach proportionate to the respective risks, currently put forward by the EC. This review identifies important elements for the case-by-case approach for the ERA that need to be taken into account in the framework for a risk-oriented regulatory approach. We also discuss that the comparison of genome-edited plants with plants developed using conventional breeding methods should be conducted at the level of a scientific case-by-case assessment of individual applications rather than at a general, technology-based level. Our considerations aim to support the development of further specific guidance for the ERA of genome-edited plants.

Genome-Edited Plants: Opportunities and Challenges for an Anticipatory Detection and Identification Framework.

It is difficult to trace and identify genome-edited food and feed products if relevant information is not made available to competent authorities. This results in major challenges, as genetically modified organism (GMO) regulatory frameworks for food and feed that apply to countries such as the member states of the European Union (EU) require enforcement based on detection. An international anticipatory detection and identification framework for voluntary collaboration and collation of disclosed information on genome-edited plants could be a valuable tool to address these challenges caused by data gaps. Scrutinizing different information sources and establishing a level of information that is sufficient to unambiguously conclude on the application of genome editing in the plant breeding process can support the identification of genome-edited products by complementing the results of analytical detection. International coordination to set up an appropriate state-of-the-art database is recommended to overcome the difficulty caused by the non-harmonized bio-safety regulation requirements of genome-edited food and feed products in various countries. This approach helps to avoid trade disruptions and to facilitate GMO/non-GMO labeling schemes. Implementation of the legal requirements for genome-edited food and feed products in the EU and elsewhere would substantially benefit from such an anticipatory framework.

Biosafety of Genome Editing Applications in Plant Breeding: Considerations for a Focused Case-Specific Risk Assessment in the EU.

An intensely debated question is whether or how a mandatory environmental risk assessment (ERA) should be conducted for plants obtained through novel genomic techniques, including genome editing (GE). Some countries have already exempted certain types of GE applications from their regulations addressing genetically modified organisms (GMOs). In the European Union, the European Court of Justice confirmed in 2018 that plants developed by novel genomic techniques for directed mutagenesis are regulated as GMOs. Thus, they have to undergo an ERA prior to deliberate release or being placed on the market. Recently, the European Food Safety Authority (EFSA) published two opinions on the relevance of the current EU ERA framework for GM plants obtained through novel genomic techniques (NGTs). Regarding GE plants, the opinions confirmed that the existing ERA framework is suitable in general and that the current ERA requirements need to be applied in a case specific manner. Since EFSA did not provide further guidance, this review addresses a couple of issues relevant for the case-specific assessment of GE plants. We discuss the suitability of general denominators of risk/safety and address characteristics of GE plants which require particular assessment approaches. We suggest integrating the following two sets of considerations into the ERA: considerations related to the traits developed by GE and considerations addressing the assessment of method-related unintended effects, e.g., due to off-target modifications. In conclusion, we recommend that further specific guidance for the ERA and monitoring should be developed to facilitate a focused assessment approach for GE plants.

Corrigendum: An EU Perspective on Biosafety Considerations for Plants Developed by Genome Editing and Other New Genetic Modification Techniques (nGMs).

[This corrects the article DOI: 10.3389/fbioe.2019.00031.].

An EU Perspective on Biosafety Considerations for Plants Developed by Genome Editing and Other New Genetic Modification Techniques (nGMs).

The question whether new genetic modification techniques (nGM) in plant development might result in non-negligible negative effects for the environment and/or health is significant for the discussion concerning their regulation. However, current knowledge to address this issue is limited for most nGMs, particularly for recently developed nGMs, like genome editing, and their newly emerging variations, e.g., base editing. This leads to uncertainties regarding the risk/safety-status of plants which are developed with a broad range of different nGMs, especially genome editing, and other nGMs such as cisgenesis, transgrafting, haploid induction or reverse breeding. A literature survey was conducted to identify plants developed by nGMs which are relevant for future agricultural use. Such nGM plants were analyzed for hazards associated either (i) with their developed traits and their use or (ii) with unintended changes resulting from the nGMs or other methods applied during breeding. Several traits are likely to become particularly relevant in the future for nGM plants, namely herbicide resistance (HR), resistance to different plant pathogens as well as modified composition, morphology, fitness (e.g., increased resistance to cold/frost, drought, or salinity) or modified reproductive characteristics. Some traits such as resistance to certain herbicides are already known from existing GM crops and their previous assessments identified issues of concern and/or risks, such as the development of herbicide resistant weeds. Other traits in nGM plants are novel; meaning they are not present in agricultural plants currently cultivated with a history of safe use, and their underlying physiological mechanisms are not yet sufficiently elucidated. Characteristics of some genome editing applications, e.g., the small extent of genomic sequence change and their higher targeting efficiency, i.e., precision, cannot be considered an indication of safety per se, especially in relation to novel traits created by such modifications. All nGMs considered here can result in unintended changes of different types and frequencies. However, the rapid development of nGM plants can compromise the detection and elimination of unintended effects. Thus, a case-specific premarket risk assessment should be conducted for nGM plants, including an appropriate molecular characterization to identify unintended changes and/or confirm the absence of unwanted transgenic sequences.

Plants Developed by New Genetic Modification Techniques-Comparison of Existing Regulatory Frameworks in the EU and Non-EU Countries.

The development of new genetic modification techniques (nGMs), also referred to as "new (breeding) techniques" in other sources, has raised worldwide discussions regarding their regulation. Different existing regulatory frameworks for genetically modified organisms (GMO) cover nGMs to varying degrees. Coverage of nGMs depends mostly on the regulatory trigger. In general two different trigger systems can be distinguished, taking into account either the process applied during development or the characteristics of the resulting product. A key question is whether regulatory frameworks either based on process- or product-oriented triggers are more advantageous for the regulation of nGM applications. We analyzed regulatory frameworks for GMO from different countries covering both trigger systems with a focus on their applicability to plants developed by various nGMs. The study is based on a literature analysis and qualitative interviews with regulatory experts and risk assessors of GMO in the respective countries. The applied principles of risk assessment are very similar in all investigated countries independent of the applied trigger for regulation. Even though the regulatory trigger is either process- or product-oriented, both triggers systems show features of the respective other in practice. In addition our analysis shows that both trigger systems have a number of generic advantages and disadvantages, but neither system can be regarded as superior at a general level. More decisive for the regulation of organisms or products, especially nGM applications, are the variable criteria and exceptions used to implement the triggers in the different regulatory frameworks. There are discussions and consultations in some countries about whether changes in legislation are necessary to establish a desired level of regulation of nGMs. We identified five strategies for countries that desire to regulate nGM applications for biosafety-ranging from applying existing biosafety frameworks without further amendments to establishing new stand-alone legislation. Due to varying degrees of nGM regulation, international harmonization will supposedly not be achieved in the near future. In the context of international trade, transparency of the regulatory status of individual nGM products is a crucial issue. We therefore propose to introduce an international public registry listing all biotechnology products commercially used in agriculture.

Herbicide resistance and biodiversity: agronomic and environmental aspects of genetically modified herbicide-resistant plants.

Farmland biodiversity is an important characteristic when assessing sustainability of agricultural practices and is of major international concern. Scientific data indicate that agricultural intensification and pesticide use are among the main drivers of biodiversity loss. The analysed data and experiences do not support statements that herbicide-resistant crops provide consistently better yields than conventional crops or reduce herbicide amounts. They rather show that the adoption of herbicide-resistant crops impacts agronomy, agricultural practice, and weed management and contributes to biodiversity loss in several ways: (i) many studies show that glyphosate-based herbicides, which were commonly regarded as less harmful, are toxic to a range of aquatic organisms and adversely affect the soil and intestinal microflora and plant disease resistance; the increased use of 2,4-D or dicamba, linked to new herbicide-resistant crops, causes special concerns. (ii) The adoption of herbicide-resistant crops has reduced crop rotation and favoured weed management that is solely based on the use of herbicides. (iii) Continuous herbicide resistance cropping and the intensive use of glyphosate over the last 20 years have led to the appearance of at least 34 glyphosate-resistant weed species worldwide. Although recommended for many years, farmers did not counter resistance development in weeds by integrated weed management, but continued to rely on herbicides as sole measure. Despite occurrence of widespread resistance in weeds to other herbicides, industry rather develops transgenic crops with additional herbicide resistance genes. (iv) Agricultural management based on broad-spectrum herbicides as in herbicide-resistant crops further decreases diversity and abundance of wild plants and impacts arthropod fauna and other farmland animals. Taken together, adverse impacts of herbicide-resistant crops on biodiversity, when widely adopted, should be expected and are indeed very hard to avoid. For that reason, and in order to comply with international agreements to protect and enhance biodiversity, agriculture needs to focus on practices that are more environmentally friendly, including an overall reduction in pesticide use. (Pesticides are used for agricultural as well non-agricultural purposes. Most commonly they are used as plant protection products and regarded as a synonym for it and so also in this text.).

Potential of genetically modified oilseed rape for biofuels in Austria: Land use patterns and coexistence constraints could decrease domestic feedstock production.

Like other EU Member States, Austria will meet the substitution target of the EU European Renewable Energy Directive for transportation almost exclusively by first generation biofuels, primarily biodiesel from oilseed rape (OSR). Genetically modified (GM) plants have been promoted as a new option for biofuel production as they promise higher yield or higher quality feedstock. We tested implications of GM OSR application for biodiesel production in Austria by means of high resolution spatially explicit simulation of 140 different coexistence scenarios within six main OSR cropping regions in Austria (2400 km2). We identified structural land use characteristics such as field size, land use diversity, land holding patterns and the proportion of the target crop as the predominant factors which influence overall production of OSR in a coexistence scenario. Assuming isolation distances of 800 m and non-GM-OSR proportions of at least 10% resulted in a loss of area for cultivation of OSR in all study areas ranging from -4.5% to more than -25%, depending on the percentage of GM farmers and on the region. We could show that particularly the current primary OSR cropping regions are largely unsuitable for coexistence and would suffer from a net loss of OSR area even at isolation distances of 400 or 800 m. Coexistence constraints associated with application of GM OSR are likely to offset possible GM gains by substantially reducing farmland for OSR cultivation, thus contradicting the political aim to increase domestic OSR area to meet the combined demands of food, feed and biofuel production.