Richard Kuper has extracted for Red-Green Labour the main points of this highly detailed article, the full text of which can be found here.
1. Myth: Many mutations occur in natural reproduction. So there’s no need to worry about those that occur as a result of the gene editing process.Facts in brief: In natural reproduction, certain regions of the organism’s DNA genetic material (genome) are protected from mutations (DNA damage). Also, the genetic variations that arise through rounds of natural reproduction are not random but are biased in the direction of adaptation and survival. This contrasts with the genome-wide mutations that are caused by gene editing processes, which are random and widespread. Some of these mutations could alter the composition of the gene-edited crop making it toxic or allergenic, resulting in a public health risk.
2. Myth: Compared with gene editing, far more mutations occur in chemical- and radiation-induced mutagenesis breeding, techniques that have been safely used for decades in crop breeding. Most of our crop plants have a mutagenesis-bred ancestor. We don’t regulate these techniques, so why regulate gene editing?
Facts in brief: Mutagenesis breeding has been practiced for decades, but was introduced before scientists understood the risks of creating widespread genetic damage in plant genomes. It has an unknown safety profile as no controlled studies have been done. It produces large numbers of deformed and non-viable plants – part of the reason why it has been little used and has produced relatively few crop varieties when compared with traditional plant breeding. Just because one risky technology (mutagenesis breeding) in the past escaped regulation doesn’t mean another risky technology (gene editing) should do so. Two wrongs don’t make a right.
3. Myth: Mutations are not bad or harmful, but drive evolution and are therefore to be welcomed.Facts in brief: Most mutations are harmful and living organisms have evolved mechanisms to minimise them. Legislators worldwide have established laws to minimise the exposure of living organisms to mutagenic (causing mutations) agents.
4. Myth: Research in animals shows that many new variants (that were not in parental animals) occur in natural reproduction and many of these are in genes. Therefore off-target mutations that occur in gene editing are not a concern.Facts in brief: Genetic variation (including in genes) through natural reproduction has evolved to bring about adaptation to environmental conditions. But this is different from the random genome-wide mutations that occur during laboratory genetic modification procedures (including gene editing), which are not governed by evolutionary forces or driven by the need to adapt to environmental conditions. These mutations, as well as the epigenetic changes that can arise from genetic modification procedures such as gene editing, can predispose animals to disease. Long-term and transgenerational research is needed to check that gene-edited animals do not possess them.
5. Myth: Gene-edited pigs have been engineered to contain a single gene knockout (gene disruption) aimed at preventing infection by a virus causing Porcine Reproductive and Respiratory Syndrome (PRRS). This is a boon to animal welfare that should be welcomed and facilitated by removing onerous regulations.Facts in brief: Given that new strains of any given virus are generated at a rapid rate, it is likely that variants of the PRRS virus (PRRSV) will quickly be selected for that bypass the single-gene block that has been engineered into the pigs. Also, regulations must require research to be carried out pre-commercialisation to ensure that the genetic engineering changes made to the genome won’t affect the animals’ health and wellbeing. Overall, the solution to the problem of livestock diseases is not to genetically engineer animals so that we can continue to raise them in inhumane conditions, but to improve the conditions in which we rear them.
6. Myth: Whole genome sequencing, which can accurately identify the full spectrum of unintended mutations at both off-target and on-target edit sites, including inadvertent insertion of foreign DNA, is too impractical and onerous to undertake for gene-edited plants.study).Facts in brief: Multiple reference genomes derived from whole genome sequencing of major crop plants are now in the public domain. Whole genome sequencing has yielded important information about the unintended effects of gene editing on the genome. In a study on gene-edited rice using the CRISPR/Cas gene editing tool, whole genome sequencing was used to investigate unintended mutations arising from different aspects of the gene editing procedure. The researchers found that the gene editing procedure (taken as a whole, namely, tissue culture and Agrobacterium-mediated cell transformation) resulted in several times more unintended mutations than were found in rice propagated through natural pollination (see Fig 2b in this
7. Myth: Plant genomes contain extensive regions of “repeat sequences”, so it is difficult to obtain an accurate picture of the whole genome. This is because standard genome sequencing technology produces short lengths of DNA sequence reads that then need to be linked up accurately, using computational tools. This can be difficult, given that stretches of repeat sequences can be present at different chromosomal locations.Facts in brief: It is feasible to compile an accurate whole genome sequence, despite long stretches of repeat sequences, as evidenced by the huge body of human and animal, as well as plant, whole genome sequences available in the public domain. Any remaining difficulties of accurately aligning whole genomes through areas of long repeat sequences are solved by the advent of long-read DNA sequencing, which provides unequivocal placement of any long stretches of repeat sequences.
8. Myth: Molecular compositional profiling methods (“omics” methods: gene expression-profiling transcriptomics, protein-profiling proteomics, and small biochemical molecule-profiling metabolomics), which some are asking to be carried out to ascertain if a gene-edited plant is equivalent to its non-gene-edited parent except for the intended gene editing outcome, would not be useful. They would just generate a large body of data that would be impossible to make sense of.Facts in brief: Molecular profiling multi-omics methods are now used by thousands of research groups around the world to gain a more comprehensive and deeper insight into the function of biological organisms and systems. The computational tools (bioinformatics and statistical methods) used to analyse the data from these molecular profiling methods are well established and allow scientists to make good sense of the data generated and its health and disease implications.
Conclusion: Gene-edited products should remain regulated
The government has always said it would be led by the science in its policymaking. In the context of the new bill, we have to ask ourselves what science the government has been led by.It is evident from the science presented above that the government is not paying attention to the objective science that graphically illustrates that gene editing is neither precise nor predictable. The technology consists of treating the organism with the gene editing tool and hoping that something useful emerges from it. Without detailed characterisation of the outcomes at both a gross and deeper molecular level (which should be made publicly available), no one can claim that a gene-edited crop or animal is as safe as one that is naturally bred. For the reasons listed above and many others, we advocate that gene-edited products remain regulated under current GMO legislation and are evaluated under a process- and a product-based regulatory system. Only such a regulatory approach is true to the science that underpins gene editing technology and can foster the public trust sought by GMO developers.