The need for assessment of risks arising from interactions between NGT organisms from an EU perspective

Abstract

Background New genomic techniques (NGTs) allow new genotypes and traits to be developed in different ways and with different outcomes compared to previous genetic engineering methods or conventional breeding (including non-targeted mutagenesis). EU GMO regulation requires an assessment of their direct and indirect effects that may be immediate, delayed or cumulative. Such effects may also result from the interactions of NGT organisms simultaneously present in a shared receiving environment or emerge from a combination of their traits. This review elaborates such potential interactions based on a literature review and reasoned scenarios to identify possible pathways to harm. Main findings NGT organisms might be introduced into the environment and food chains on a large-scale, involving many traits, across a broad range of species and within short periods of time. Unavoidably, this would increase the likelihood that direct or indirect effects will occur through interactions between NGT organisms that are, for example simultaneously present within a shared environment. It has to be assumed that the cumulative effects of these NGT organisms may exceed the sum of risks identified in the distinct ‘events’. Consequently, risk assessors and risk managers not only need to consider the risks associated with individual NGT organisms (‘events’), but should also take account of risks resulting from their potential interactions and combinatorial effects. In addition, a prospective technology assessment could help the risk manager in defining criteria to minimize potential unintended interactions between NGT organisms through limiting the scale of releases. Conclusions If genetically engineered (GE) organisms derived from NGTs are released into the environment, their potentially negative impacts need to be minimized. As with all GE organisms, it is, therefore, crucial to not only assess the risks of the individual events, but also their potential interactions which can trigger direct and indirect effects with adverse impacts. It is necessary to develop hypotheses and specific scenarios to explore interactions between NGT organisms and possible pathways to harm from the perspective of the precautionary principle. In addition, the introduction prospective technology assessment could provide an instrument for the risk manager to control the scale of releases of NGT organisms.

A perspective from the EU: unintended genetic changes in plants caused by NGT—their relevance for a comprehensive molecular characterisation and risk assessment

“…Thus, in most cases, the result of the first step of the CRISPR/Cas application is a transgenic plant which may show a broad range of unintended genetic changes, which may be different to those emerging from conventional breeding, as for example discussed by Latham et al, 2006 and more recently confirmed by Yue et al (2022) . As recently summarized by Koller et al (2023) , such effects may be linked to epigenetic regulation, the disruption of genes, position effects, open reading frames, the unintended introduction of additional genes, changes in gene expression, genomic interactions which can involve plant constituents, or plant composition and agronomic characteristics ( Forsbach et al, 2003 ; Makarevitch et al, 2003 ; Windels et al, 2003 ; Rang et al, 2005 ; Gelvin, 2017 ; Jupe et al, 2019 ; Liu et al, 2019 ; Chu and Agapito-Tenfen, 2022 ; Yue et al, 2022 ). There are several studies showing that the problem of unintended insertion of transgenes is relevant to NGT applications in plants ( Li et al, 2015 ; Braatz et al, 2017 ; Biswas et al, 2020 ; Michno et al, 2020 ) or also animals ( Norris et al, 2020 ).…”

“…In short, and as summarized also by Kawall (2019) and Koller et al (2023) , site directed nucleases (SDN), such as CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR associated) ( Jinek et al, 2012 ), are highly relevant in this context: they are designed to target specific DNA sequences in the genome to knock out gene functions (i.e. SDN-1) or to introduce specific changes of particular nucleotides (i.e.…”

“…It should not be overlooked that several databases show that there are dozens of current NGT projects using species such as oilseed rape ( Brassica napus ), tomato ( Solanum lycopersicum ) or wheat ( Triticum aestivum ) [for example see ( Koller et al, 2023 )]. In this respect, it is necessary to consider the overall gene pool of the species concerned.…”

“…For the purposes of this review, we use the same specific terminology as Koller et al, 2023 to distinguish between several categories of GMOs belonging to plants ( Koller et al, 2023 ): 1) EU GMO regulation refers to GMOs which have to undergo mandatory approval processes and other GMOs which are exempt from these approval processes, e.g. plants derived from physical and chemical mutagenesis.…”

The recent possible strategies for breeding ultraviolet-B-resistant crops

“…Thorough risk assessments need to be carried out in order to assess potential threats to the environment and public health. This involves determining whether the modified crops are allergenic and whether there may be unforeseen side effects [ 102 ]. It is important to put strategies like monitoring and containment measures into practice to lessen these risks.…”