Revisions to USDA biotechnology regulations: The SECURE rule.

In keeping with the directive in Executive Order 13874 (Modernizing the Regulatory Framework for Agricultural Biotechnology Products) to adopt regulatory approaches that are proportionate to risk and avoid arbitrary distinctions across like products, the US Department of Agriculture (USDA) revised its biotechnology regulations by promulgating the Sustainable, Ecological, Consistent, Uniform, Responsible, and Efficient (SECURE) rule. Specifically, the SECURE rule 1) establishes exemptions for plants modified by genetic engineering where the modification could otherwise have been made through conventional breeding, 2) uses risk posed by the introduced trait to determine whether an organism is regulated, rather than relying on whether the organism was developed using a plant pest, and 3) provides a mechanism for a rapid initial review to efficiently distinguish plants developed using genetic engineering that do not pose plausible pathways to increased plant pest risk from those that do. As a result of the focused oversight on potentially riskier crops developed using genetic engineering, USDA is expected to improve the efficiency and effectiveness of its oversight program. The reduced regulatory burden is expected to promote innovation by expanding the number and diversity of developers to include smaller businesses and academics and to increase the number and variety of traits being developed through biotechnology.

CRISPR/Cas systems: opportunities and challenges for crop breeding.

Increasing crop production to meet the demands of a growing population depends largely on crop improvement through new plant-breeding techniques (NPBT) such as genome editing. CRISPR/Cas systems are NPBTs that enable efficient target-specific gene editing in crops, which is supposed to accelerate crop breeding in a way that is different from genetically modified (GM) technology. Herein, we review the applications of CRISPR/Cas systems in crop breeding focusing on crop domestication, heterosis, haploid induction, and synthetic biology, and summarize the screening methods of CRISPR/Cas-induced mutations in crops. We highlight the importance of molecular characterization of CRISPR/Cas-edited crops, and pay special attentions to emerging highly specific genome-editing tools such as base editors and prime editors. We also discuss future improvements of CRISPR/Cas systems for crop improvement.

New plant breeding techniques and their regulatory implications: An opportunity to advance metabolomics approaches.

Over the previous decades, biotechnological innovations have led to improved agricultural productivity, more nutritious foods and lower chemical usage. Both in western societies and Low Medium Income Countries (LMICs). However, the projected increases in the global population, means the production of nutritious food stuffs must increase dramatically. Building on existing genetic modification technologies a series of New Plant Breeding Technologies (NPBT) has recently emerged. These approaches include, Agro-infiltration, grafting, cis and intragenesis and gene editing technologies. How these new techniques should be regulated has fostered considerable debate. Concerns have also been raised, to ensure over-regulation does not arise, creating administrative and economic burden. In this article the existing landscape of genetically modified crops is reviewed and the potential of several New Plant Breeding Techniques (NPBT) described. Metabolomics is an omic technology that has developed in a concurrent manner with biotechnological advances in plant breeding. There is potentially further opportunities to advance our metabolomic technologies to characterise the outputs of New Plant Breeding Technologies, in a manner that is beneficial both from an academic, biosafety and industrial perspective.

Fruit crops in the era of genome editing: closing the regulatory gap.

The conventional breeding of fruits and fruit trees has led to the improvement of consumer-driven traits such as fruit size, yield, nutritional properties, aroma and taste, as well as the introduction of agronomic properties such as disease resistance. However, even with the assistance of modern molecular approaches such as marker-assisted selection, the improvement of fruit varieties by conventional breeding takes considerable time and effort. The advent of genetic engineering led to the rapid development of new varieties by allowing the direct introduction of genes into elite lines. In this review article, we discuss three such case studies: the Arctic® apple, the Pinkglow pineapple and the SunUp/Rainbow papaya. We consider these events in the light of global regulations for the commercialization of genetically modified organisms (GMOs), focusing on the differences between product-related systems (the USA/Canada comparative safety assessment) and process-related systems (the EU "precautionary principle" model). More recently, genome editing has provided an efficient way to introduce precise mutations in plants, including fruits and fruit trees, replicating conventional breeding outcomes without the extensive backcrossing and selection typically necessary to introgress new traits. Some jurisdictions have reacted by amending the regulations governing GMOs to provide exemptions for crops that would be indistinguishable from conventional varieties based on product comparison. This has revealed the deficiencies of current process-related regulatory frameworks, particularly in the EU, which now stands against the rest of the world as a unique example of inflexible and dogmatic governance based on political expediency and activism rather than rigorous scientific evidence.

Rhizogenic agrobacteria as an innovative tool for plant breeding: current achievements and limitations.

Compact plant growth is an economically important trait for many crops. In practice, compactness is frequently obtained by applying chemical plant growth regulators. In view of sustainable and environmental-friendly plant production, the search for viable alternatives is a priority for breeders. Co-cultivation and natural transformation using rhizogenic agrobacteria result in morphological alterations which together compose the Ri phenotype. This phenotype is known to exhibit a more compact plant habit, besides other features. In this review, we highlight the use of rhizogenic agrobacteria and the Ri phenotype with regard to sustainable plant production and plant breeding. An overview of described Ri lines and current breeding applications is presented. The potential of Ri lines as pre-breeding material is discussed from both a practical and legal point of view.

Options to Reform the European Union Legislation on GMOs: Scope and Definitions.

We discuss options to reform the EU genetically modified organisms (GMO) regulatory framework, make risk assessment and decision-making more consistent with scientific principles, and lay the groundwork for international coherence. The first in a three-part series, this article focuses on reform options related to the scope of the legislation and the GMO definition.

Will the EU stay out of step with science and the rest of the world on plant breeding innovation?

Innovations in plant breeding like genome editing methods raised questions about the adequacy of established regulatory policies for plant breeding and biotechnology in view of these new breeding methods and the resulting products. Most countries follow the principle approach that only those plants will be regulated under biotech regulations that include a novel combination of genetic material following the Cartagena protocol. In contrast to this, the European Court of Justice interpreted the current EU biotech regulations in a way that these also apply to plants resulting from new mutagenesis breeding, even if these plants are indistinguishable from conventionally bred plants. This ruling created strong reactions and concerns stating that recent technical developments have made the EU GMO Directive no longer fit for purpose. The article describes ongoing policy developments on EU level that might result in an update of current regulations.

Canadian regulatory aspects of gene editing technologies.

The development of gene editing techniques, capable of producing plants and animals with new and improved traits, is revolutionizing the world of plant and animal breeding and rapidly advancing to commercial reality. However, from a regulatory standpoint the Government of Canada views gene editing as another tool that will join current methods used to develop desirable traits in plants and animals. This is because Canada focusses on the potential risk resulting from the novelty of the trait, or plant or animal product entering the Canadian environment or market place, rather than the process or method by which it was created. The Canadian Food Inspection Agency is responsible for the regulation of the environmental release of plants with novel traits, and novel livestock feeds, while Health Canada is responsible for the regulation of novel foods. Environment and Climate Change Canada, in partnership with Health Canada, regulates modified animals for entry into the environment. In all cases, these novel products may be the result of conventional breeding, mutagenesis, recombinant DNA techniques or other methods of plant or animal breeding such as gene editing. This novelty approach allows the Canadian regulatory system to efficiently adjust to any new developments in the science of plant and animal breeding and allows for risk-appropriate regulatory decisions. This approach encourages innovation while maintaining science-based regulatory expertise. Canadian regulators work cooperatively with proponents to determine if their gene editing-derived product meets the definition of a novel product, and whether it would be subject to a pre-market assessment. Therefore, Canada's existing regulatory system is well positioned to accommodate any new innovations or technologies in plant or animal breeding, including gene editing.

Genome Editing in Agriculture: Technical and Practical Considerations.

The advent of precise genome-editing tools has revolutionized the way we create new plant varieties. Three groups of tools are now available, classified according to their mechanism of action: Programmable sequence-specific nucleases, base-editing enzymes, and oligonucleotides. The corresponding techniques not only lead to different outcomes, but also have implications for the public acceptance and regulatory approval of genome-edited plants. Despite the high efficiency and precision of the tools, there are still major bottlenecks in the generation of new and improved varieties, including the efficient delivery of the genome-editing reagents, the selection of desired events, and the regeneration of intact plants. In this review, we evaluate current delivery and regeneration methods, discuss their suitability for important crop species, and consider the practical aspects of applying the different genome-editing techniques in agriculture.

Maximum vs minimum harmonization: what to expect from the institutional and legal battles in the EU on gene editing technologies.

New plant-breeding technologies (NPBTs), including gene editing, are widely used and drive the development of new crops. However, these new technologies are disputed, creating uncertainty in how their application for agricultural and food uses will be regulated. While in North America regulatory systems respond with a differentiated approach to NPBTs, the Court of Justice of the European Union (EU) has in effect made most if not all NPBT subject to the same regulatory regime as genetically modified organisms (GMOs). This paper discusses from a law and economics point of view different options that are available for the EU's multi-level legal order. Using an ex-ante regulation versus ex-post liability framework allows the economic implications of different options to be addressed. The results show that under current conditions, some options are more expensive than others. The least costly option encompasses regulating new crops derived from NPBTs similar to those used in 'conventional' breeding. The current regulatory situation in the EU, namely making the use of NPBTs subject to the same conditions as GMOs, is the most costly option. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Certain new plant breeding techniques and their marketability in the context of EU GMO legislation - recent developments.

The comparatively low adoption rate of GMO products in the European Union (EU) market seems to be connected with the strictness of authorization regulations and inefficiency of the authorization process itself. These problems will apply to any product deemed to be a GMO that could potentially be marketable in the EU. Since modern methods of plant breeding involving oligonucleotide-directed mutagenesis (ODMs) or site-directed nucleases (SDNs), including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), are becoming ever more popular, it is crucial to establish whether the products of such new breeding techniques (NBTs), in particular those which involve precise methods of mutagenesis, are exempted from the EU legislation on GMOs or not. Legal uncertainty as to their status may result in reluctance to invest in such methods and develop them further. Here, developments are presented in the legal classification of certain NBTs products in the context of recent decisions and jurisprudence. The socioeconomic aspects of GMO adoption in both global and European contexts are discussed. The legal and practical landscape of GMO regulation in the EU is presented and how it may pose an obstacle to investment and the development of new products. The latest jurisprudence (e.g., Case C-528/16) [1] on the interpretation of the legal concept of GMOs and the scope of the legislation are analyzed, with the conclusion that the strict regulations will probably also apply to products of the NBTs involving precise methods of mutagenesis. This in turn will probably result in the restriction of their application in the development of new plant varieties in the EU.

The evolving EU regulatory framework for precision breeding.

Plant breeding has always relied on progress in various scientific disciplines to generate and enable access to genetic variation. Until the 1970s, available techniques generated mostly random genetic alterations that were subject to a selection procedure in the plant material. Recombinant nucleic acid technology, however, started a new era of targeted genetic alterations, or precision breeding, enabling a much more targeted approach to trait management. More recently, developments in genome editing are now providing yet more control by enabling alterations at exact locations in the genome. The potential of recombinant nucleic acid technology fueled discussions about potentially new associated risks and, starting in the late 1980s, biosafety legislation for genetically modified organisms (GMOs) has developed in the European Union. However, the last decade has witnessed a lot of discussions as to whether or not genome editing and other precision breeding techniques should be encompassed by the EU GMO legislation. A recent ruling from the Court of Justice of the European Union indicated that directed mutagenesis techniques should be subject to the provisions of the GMO Directive, essentially putting many precision breeding techniques in the same regulatory basket. This review outlines the evolving EU regulatory framework for GMOs and discusses some potential routes that the EU may take for the regulation of precision breeding.

The Open Source Seed Licence: A novel approach to safeguarding access to plant germplasm.

The laws to secure intellectual property rights on plant germplasm have been strongly developed in parallel to the ongoing seed market consolidation. Germplasm as a commons, i.e., a natural resource accessible to all members of a society, receives almost no legal protection. On the other hand, the use of germplasm and released cultivars in breeding is increasingly restricted by intellectual property rights. In this study, approaches to open source plant germplasm are discussed, and the Open Source Seed (OSS) Licence is introduced and analysed. The OSS Licence was developed by an interdisciplinary working group of plant breeders, agricultural scientists, lawyers, and commons experts in Europe. The aim is to protect germplasm as a commons, support the free exchange of germplasm, stimulate plant breeding, reduce costs, and accelerate innovation. The OSS Licence is a legal tool and novel approach that extends its reach on derivatives of licenced germplasm. It is compatible with current seed laws. Effects on the access to plant germplasm, on breeding for diverse pedoclimatic environments, socioeconomic systems, and on biodiversity as a whole can first show after a few breeding cycles. The impact of open source germplasm on these aspects needs to be monitored carefully.

Responsible decision-making for plant research and breeding innovations in the European Union.

Plant research and breeding has made substantial technical progress over the past few decades, indicating a potential for tremendous societal impact. Due to this potential, the development of policies and legislation on plant breeding and the technical progress should preferably involve all relevant stakeholders. However, we argue here that there is a substantial imbalance in the European Union (EU) regarding the influence of the various stakeholder groups on policy makers. We use evidence from three examples in order to show that the role of science is overlooked: 1) important delays in the decision process concerning the authorization of genetically modified (GM) maize events, 2) the significance attributed to non-scientific reasons in new legislation concerning the prohibition of GM events in EU member states, and 3) failure of the European Commission to deliver legal guidance to new plant breeding techniques despite sufficient scientific evidence and advisory reports. We attribute this imbalance to misinformation and misinterpretation of public perceptions and a disproportionate attention to single outlier reports, and we present ideas on how to establish a better stakeholder balance within this field.

Genome editing of crops: A renewed opportunity for food security.

Genome editing of crop plants is a rapidly advancing technology whereby targeted mutations can be introduced into a plant genome in a highly specific manner and with great precision. For the most part, the technology does not incorporate transgenic modifications and is far superior to conventional chemical mutagenesis. In this study we bring into focus some of the underlying differences between the 3 existing technologies: classical plant breeding, genetic modification and genome editing. We discuss some of the main achievements from each area and highlight their common characteristics and individual limitations, while emphasizing the unique capabilities of genome editing. We subsequently examine the possible regulatory mechanisms which governments may be inclined to use in assessing the status of genome edited products. If assessed on the basis of their phenotype rather than the process by which they are obtained, these products will be categorized as equivalent to those produced by classical mutagenesis. This would mean that genome edited products will not be subject to the restrictions imposed on genetically modified products, except in some cases where the mutation involves a large sequence insertion into the genome. We conclude by examining the potential of societal acceptance of genome editing technology, reinforced by a scientific perspective on promoting such acceptance.

A research program for the socioeconomic impacts of gene editing regulation.

Gene editing technologies are a group of recent innovations in plant breeding using molecular biology, which have in common the capability of introducing a site-directed mutation or deletion in the genome. The first cases of crops improved with these technologies are approaching the market; this has raised an international debate regarding if they should be regulated as genetically modified crops or just as another form of mutagenesis under conventional breeding. This dilemma for policymakers not only entails issues pertaining safety information and legal/regulatory definitions. It also demands borrowing tools developed in the field of social studies of science and technology, as an additional basis for sound decision making.