TWN Info Service on Biosafety
23 January 2024
Third World Network
www.twn.my
Dear Friends and Colleagues
Robust Risk Assessment Urgently Needed for All New Genetically Engineered Plants
The Environment Agency of Austria has co-published a study which analyses the potential risks of products of new genomic techniques (NGT). Like classical genetic engineering, NGTs are also based on biological processes that cannot guarantee absolute precision. A wide range of unintended genetic changes are possible; these include smaller or larger genetic changes adjacent to the target sequence, i.e. unintended “on-target” mutations. Unintended effects are also caused by the fact that the intended genetic changes will often not only result in the expression of a specific desired characteristic, but will simultaneously affect other functions or traits in the modified cells or organisms.
According to a 2018 ruling by the European Court of Justice, a risk assessment is currently mandatory for NGT products in the EU. However, in July 2023, the European Commission (EC) presented a draft regulation that would deviate significantly from the existing approach.
The study stresses the urgent need for a uniform, robust risk assessment of all NGT plants. To address risk issues of NGT plants comprehensively, a precautionary, case-specific approach, taking into account the available experience with comparable products, is needed. The risk assessment for NGT products should be based on similar principles as adopted for GMOs and should address nutritional safety and quality, as well as effects on the environment. The assessment also needs to address off-target modifications and other unintended genetic changes, which remain in the final NGT product and might result in adverse effects.
The current regulatory proposal by the EC would result in significant undesirable effects on a whole range of aspects including, but not limited to safety and consumer rights. These include adding significant additional economic burdens on all agricultural production systems that are not allowed to use GMOs and NGT plants or refrain from using them, such as organic farming, while the abolition of labeling for food and feed products from NGT plants would severely restrict consumers’ freedom of choice. The study concludes that it is important to ensure that the weaknesses of the proposed regulation are addressed by a comprehensive revision and that any further proposals aimed at an even more far-reaching deregulation be rejected.
With best wishes,
Third World Network
NEW GENETIC ENGINEERING – POSSIBLE UNINTENDED EFFECTS
Michael Eckerstorfer, Andreas Heissenberger
INFORMATIONEN ZUR UMWELTPOLITIK Volume 28
AK Wien and the Environment Agency of Austria
https://emedien.arbeiterkammer.at/viewer/image/AC16982244/6/
November 2023
SUMMARY
How potential risks of NGT products are dealt with is an essential aspect of the application of “new genetic engineering” techniques (or “new genomic techniques” or NGTs, as they are called by the European Commission) in agriculture and food production. Although the safety of NGT products is of considerable importance for developers, consumers and legislators, respectively, this aspect is not in the focus of the current debate concerning a proposal of the European Commission for a new regulation for NGT products. Therefore, this study examines this aspect on the basis of selected, representative examples of NGT products. The analysis intends to direct the focus on the issue of unintended effects, which may be associated with NGT products.
In public, the developers argue that new genetic engineering, in contrast to classical genetic engineering, is much more targeted than other approaches. They also emphasize that the genetic changes induced by such techniques would be comparable to changes that could also occur in conventionally bred varieties. However, such arguments ignore the fact that NGTs are also based on biological processes that cannot guarantee absolute precision. In addition, the level of precision for the introduction of genetic changes at specific locations in the DNA of the modified organisms bears no relation to the safety or the risk of the traits, which are developed in these NGT organisms. The present study therefore underlines previous statements of scientists and consumer organisations that unintended and not fully predictable effects can also occur with NGT products.
Such effects may be due to unintended genetic changes caused by cell culture and transformation methods, which are also used for the production of classical GMOs (genetically modified organisms containing transgenic DNA). For example, in the case of hornless cows which were produced by means of targeted mutagenesis (genome editing), a later independent review by experts from the US Food and Drug Administration (FDA) found that foreign DNA sequences, including an antibiotic resistance gene, had been unintentionally introduced into the DNA of the modified cows. Moreover, due to the technique used for the editing plant genomes mutations can also be induced at DNA sites that are similar, but not identical to the intended target site – so-called “off-target” mutations. However, the occurrence of such off-target mutations is rarely investigated comprehensively enough and at the right time of the development process of a NGT plant. Many of these studies are conducted to rather optimize the genome editing approach than to monitor whether off-target mutations which may lead to adverse effects are still present in the NGT plant immediately prior to commercialisation of the NGT product. In any case, a growing body of scientific research indicates that a wide range of unintended genetic changes are possible through the application of NGTs. These include smaller or larger genetic changes adjacent to the target sequence, i.e. unintended “on-target” mutations. In extreme cases, the changes to the target sequence can trigger cascading rearrangements of parts of the affected chromosomes. Although unintended off- and on-target mutations with adverse effects do not occur in all genome editing approaches, the probability is high enough to conclude that the occurrence of unintended DNA changes needs to be addressed during a risk assessment.
In addition to these technology-related changes, unintended effects are also caused by the fact that the intended genetic changes will often not only result in the expression of a specific desired characteristic, but will simultaneously affect other functions or traits in the modified cells or organisms. These unintended “side effects” are often not predictable, mainly due to the limited knowledge regarding the complex interactions within higher organisms and the manifold interactions between different organisms in the environment. If a number of different, independent modifications is introduced simultaneously, the possibility for unintended side effects is even higher. Such multiplexing approaches which allow for the simultaneous targeted mutagenesis of several different DNA target sites are currently possible without too much technical difficulty and plants harboring complex modifications can be produced relatively quickly. However, plants with similar genetic modifications may not be produced by conventional breeding approaches at all or they could only be produced with a disproportionately high effort.
ARE LOWER SAFETY STANDARDS TO BE EXPECTED FOR NGT PRODUCTS?
Under the existing legislative framework for GMOs in the European Union, a risk assessment must be carried out prior to authorisation for deliberate release or commercialisation to determine whether GM products may cause adverse effects on human and animal health and the environment as a result of unintended modifications. According to a 2018 ruling by the European Court of Justice, such risk assessment is currently mandatory for NGT products as well. However, in July 2023, the European Commission presented a draft regulation that would deviate significantly from the existing approach. The draft regulation would create two categories of NGT plants:
- NGT plants of the first category (NGT 1) – which includes more than 90% of all NGT plants according to the proposed definition – would no longer be subject to the obligations that currently exist for GMOs, e.g. with regard to risk assessment, post-authorisation environmental monitoring, labeling of all GM products, and cultivation requirements (coexistence and “opt-out measures” proposed by EU Member States).
- NGT plants of the second category (NGT 2) comprise a smaller group of NGT products with very complex modifications, i.e. plants with more than 20 different genetic modifications. In principle, similar provisions as for GMOs apply, but the respective requirements for NGT 2 plants may be less robust regarding risk assessment, monitoring, re-authorisation and the provision of detection methods by the developer.
EXAMPLES SHOW THAT THE ASSESSMENT OF UNINTENDED EFFECTS OF NGT PLANTS IS URGENTLY NEEDED
In order to assess how current standards for risk assessment of NGT products may be adversely impacted by the proposed new regulation, four NGT products were considered as examples. These examples include NGT plants that are already marketed in other non-EU countries, such as Japan, as well as plants whose development is described in the scientific literature, and which could be marketed in the future. The examples include three NGT 1 plants and one NGT 2 plant. They cover different areas of application, including two NGT plants with changes in their composition (NGT 1 and NGT 2), an NGT 1 plant with increased tolerance to environmental stress, and an example of a NGT 1 tomato plant, which was rapidly developed of from a wild tomato species. The selected examples only partially cover the wide variety of developments; however, the conclusions derived are relevant for all NGT plants.
- NGT Tomatoes with increased gamma-aminobutyric acid (GABA) content – NGT 1
This NGT tomato is an example of a “functional food”; the increased GABA content is thought to have beneficial effects in people suffering from high blood pressure.
It is however unclear, whether adverse effects on other populations, especially vulnerable groups, may be associated with the consumption of these tomatoes. In tomato plants, GABA also influences a variety of different metabolic processes, and exerts effects on microorganisms and insects; unintended effects of elevated GABA levels on plant shape and growth have been shown.
- NGT Wheat with lower gluten content – NGT 2
In these NGT wheat plants, more than 30 gluten genes were deactivated to reduce the total gluten content. However, it is uncertain whether individuals suffering from gluten intolerance due to an autoimmune disease will tolerate the NGT wheat with reduced gluten content as well as other, gluten-free cereals. It must also be assessed whether gluten protein variants expressed as a result of the genetic changes are safe and whether an increased production of other wheat proteins with potentially allergic effects would occur in the NGT wheat. Gluten proteins also positively influence the tolerance of wheat plants to environmental stress, such as heat and drought stress. It is unclear whether the NGT wheat is as tolerant to such environmental stressors as other wheat varieties.
- NGT rice with increased tolerance to climate and salt stress – NGT 1
Genetic modification of a regulatory gene in NGT rice under controlled conditions results in increased resistance to increased salt concentrations in the soil, which will occur more frequently in the course of climate change.
However, it is not clear whether under changing field conditions these positive effects can also be realised without possible yield losses. Furthermore, it is unclear which indirect changes with regard to composition and food safety occur as a result of the genetic modification.
- “De Novo Domesticated” NGT tomatoes with increased resistance to plant diseases – NGT 1
Through introducing several independent genetic changes to genes that affect the shape and development or reproductive characteristics of tomato plants, a wild tomato can be turned into a plant with high similarity to cultivated tomato varieties in a single step – the conventional development of modern tomatoes by crossing and selection by comparison has taken almost 10,000 years. Desirable traits which are present in the wild plant such as lower disease susceptibility are retained.
A comprehensive risk assessment would have to assess whether the safety and wholesomeness of the NGT tomato may be adversely affected by other traits derived from the wild plant in comparison with tomato varieties cultivated currently for food production.
RECOMMENDATIONS
An intended objective of the proposed new regulation is to ensure a high level of safety for NGT plants, taking into account the precautionary principle. However, this objective is not compatible with the proposed waiver of a comprehensive risk assessment for NGT 1 plants as currently implemented for GMOs and the possible weakening of risk assessment requirements for NGT 2 plants.
- A uniform, robust risk assessment of all NGT plants is still urgently needed.
Even a cursory examination of a few examples of NGT plants illustrates that the safety of individual products can only be guaranteed by means of a case-specific assessment that focuses on plausible hazards, which may be associated with a respective NGT plant. In this risk assessment, all possible unintended effects on health and the environment must be taken into account – regardless of whether they are caused by the technology used to generate the NGT plant or by the characteristics of the developed traits.
In view of the existing knowledge gaps and uncertainties, general, theoretical considerations and the reference to existing requirements for conventional plants are absolutely not sufficient. Neither the requirements for variety registration nor the assessment of health risks of individual NGT products in the context of the novel food legislation are suitable nor comprehensive enough to ensure the safety of NGT plants concerning all risk issues.
In addition to a reduction of safety standards – especially for all NGT 1 plants and thus for the vast majority of NGT products, which may be expected in the future – the proposed regulation would have a variety of other undesirable effects:
- The implementation of the regulation would pose significant additional economic burdens on all agricultural production systems that are not allowed to use GMOs and NGT plants or refrain from using them, such as organic farming. It would thus jeopardise precisely those production systems that are important for a further sustainable development in agriculture.
- The abolition of labeling for food and feed products from NGT 1 plants would severely restrict consumers’ freedom of choice.
- The rights of the Member States would be considerably weakened by the planned new regulation – however, they would have to assume additional responsibility, e.g. for the implementation of coexistence regulations for NGT 2 plants, without having the necessary preconditions at hands, e.g. the availability of detection methods.
- The proposed regulation does not contain measures that would ensure plant breeders’ access to plant material for further development if this access is restricted by patents.
It is therefore important to ensure that the weaknesses of the proposed regulation are addressed by a comprehensive revision and that any further proposals aimed at an even more far-reaching deregulation are rejected.