Combinatorial effects increase risks in food production
Currently, more than 90 different transgenic plants (events), or their harvest, have already been approved for import into the EU as food and feed. The European Food Safety Authority (EFSA) has in each case carried out a risk assessment as part of the individual approval procedure, including determining potential effects of the import and consumption of food and feed derived from genetically engineered plants on human, animal and environmental health. The aim of this procedure is to ensure that only those genetically engineered plants are approved which are safe for humans, animals and the environment, and which will not cause any consequential damage.
The cultivation of transgenic plants has led to an increase in herbicide-resistant weeds and the adaptation of pests. The answer of the biotech industry to these developments is to rearm transgenic plants by combining several genetic engineering traits in one plant (so-called 'stacked events'). This has led to a veritable arms race in the fields, with individual varieties currently producing up to six insecticides and containing resistance to several herbicides. Stacked events now account for the clear majority of approvals, including in the EU. This also poses new challenges for the risk assessment of the food and feed produced from these plants, as interactions between multiple Bt toxins or pesticides are much more difficult to assess than the risks associated with individual active substances. The combinatorial effect of the individual insecticides and herbicides can also be mutually amplified under certain circumstances, whereby the possible health effects can exceed the sum of the individual substances. The effects can also be triggered indirectly if, for example, the composition of the microorganisms in the gut (microbiome) changes as a result of consuming these products. This is shown in numerous studies, especially for the broad-spectrum herbicide glyphosate. Amongst others, this could promote chronic inflammatory processes, e. g. in the gastrointestinal tract. Interactions can occur with the Bt toxins, amongst others, which are known to be capable of causing immune responses. So far, neither EFSA nor the industry have investigated any of these effects more closely. For example, the EU does not request empirical studies on the overall toxicity of 'stacked events', which typically contain mixtures of residues from spraying with various herbicides in combination with Bt-toxins produced by the plants. Mixtures of transgenic plants in food and feed are also not subjected to any additional risk assessment. Consequently, possible (negative) combinatorial effects of the various events in food and feed are being disregarded in the authorisation procedures.
Uncertainties with regard to the health risks of food and feed have increased since the introduction of genetic engineering – this is due to insufficient examination of combinatorial effects. The increasing number of approvals means that new cocktails of herbicide residues and insect toxins are also being imported with the plants. As a result, risks can accumulate unnoticed in the food chain, and thus lead to an increase in health problems when the corresponding products are consumed. Many metabolic or immune diseases in humans and animals have multiple and complex causes. It cannot be ruled out that the consumption of products from genetically engineered plants may play a part in this. More detailed, in-depth investigations are therefore essential. The introduction of plants from new genetic engineering also raises the question of how possible combinatorial effects can be assessed when consuming these plants.
CRISPR-Tomatoes: Combinatorial effects can jeopardise food safety
NGTs are currently being used to change the agronomic and health-related properties of tomato plants. These developments are anticipated within a few years. In contrast, conventional methods sometimes require decades of breeding or are simply not possible. The improved composition and physiological properties of the NGT tomato plants are expected to make them particularly healthy and sustainable.
There are currently a number of projects aiming to improve tomato plants: for example, several genes were knocked out in a wild tomato variety to change growth habit, composition as well as the number, size and shape of the fruits. However, because the composition of the ingredients in these tomatoes is so different compared to commercially available tomatoes, the European Food Safety Authority (EFSA) identifies the need for risk assessment of these NGT plants.
Other NGT tomatoes have been developed to have a higher concentration of vitamins or blood pressure-lowering properties. GABA tomatoes were one of the first NGT plants to be brought to market; they are sold in Japan as a lifestyle product. However, these tomatoes were not tested by the authorities for 'risks and side effects' before being authorised. GABA in plants is essential in a variety of metabolic pathways, and an altered GABA content can, therefore, influence environmental interactions as well as other ingredients in the tomatoes and their physiological compatibility.
Further objectives of new genetic engineering relate to the cultivation and harvesting of tomatoes. Some of the products that could be commercialised in the next few years include 'easy to pick tomatoes' (easier harvesting), 'small bushy tomatoes' (particularly suitable for 'urban gardening') or 'vitamin D tomatoes' (increased vitamin D content).
Apart from food safety, the risks associated with NGT tomatoes include interactions with the environment (such as interactions with pollinators or soil organisms) and sensitivity to environmental stress.
Many NGT tomatoes could soon be grown and sold for consumption. They could then, for example, be mixed into salads without first being tested for maximum dosage or combinatorial effects. At present, different tomato varieties can be arbitrarily combined in tomato salads or otherwise combined with different foods. In future, NGT tomatoes with an increased vitamin content could, for instance, cause problems if they are eaten in combination with other foods containing vitamins or with food supplements. In addition, mixing genetically engineered tomatoes, e. g. with a higher content of GABA, vitamin D or other physiologically-active ingredients, raises new questions about food safety, especially in regard to their long-term effects. Other undesirable changes in the composition of the fruits should also be taken into account, as some of these are so complex that the overall effects are difficult to assess.
Even if individual tomato varieties are considered safe, new uncertainties and risks may arise from the combination of their properties. Therefore, a mandatory approval process will continue to be necessary in the future, including risk assessment of the individual NGT tomatoes and investigation of possible combinatorial effects in relation to potential environmental interactions or other NGT organisms.