The development of New Genomic Techniques (NGT) wheat, utilizing CRISPR technology to reduce asparagine levels — a precursor to acrylamide formation — has garnered significant attention in the agricultural and scientific communities.
This article critically examines Rothamsted Research’s gene-edited wheat project, focusing on the technical challenges of foreign DNA removal, regulatory implications, and the viability of natural alternatives.
The NGT wheat project and Its challenges
The Rothamsted Research team, led by Professor Nigel Halford, has been developing gene-edited (NGTs) wheat varieties with reduced levels of asparagine, an amino acid that serves as a precursor to acrylamide formation during high-temperature cooking processes (Kaur et al., 2024). Asparagine plays a crucial role in plant nitrogen metabolism and transport, but when wheat products are heated at high temperatures, it can be converted to acrylamide, which has been classified as a ‘probable carcinogen’ by some health authorities though Cancer Research UK has described the idea that acrylamide in burnt food causes cancer as a ‘food myth’ (Cancer Research UK, 2024).
Recent reports indicate that researchers are experiencing difficulties removing foreign DNA introduced during the gene-editing process. As reported in Euro News and cited by GMWatch, ‘Once the edit is complete, the GM components are bred out, leaving a genome-edited but GMO-free plant. Removing the GM elements, however, turned out to be challenging‘ (GMWatch, 2025). The researchers have acknowledged this challenge, with Professor Michael Antoniou noting that ‘It is well known among genetic engineering scientists that foreign DNA, either in the form of complete genes or fragments introduced during the gene editing process, is very difficult to remove from gene-edited products‘.
This is not the first hurdle for the project. Previous testing revealed an additional issue: poor germination rates in the gene-edited seeds. Interestingly, this problem ‘can be reversed by treatment with low concentrations of asparagine‘. This creates a paradoxical situation where wheat engineered to contain low levels of asparagine requires asparagine supplementation to germinate properly.
The science behind the gene-edited wheat
The technical approach used by the Rothamsted team involves the CRISPR-Cas9 gene-editing tool to target the asparagine synthetase gene, TaASN2, in wheat. The methodology employed in the research was detailed in several scientific publications, including the seminal work by Raffan et al. (2021) and the field trial results published in 2023.
In the laboratory phase, researchers used a targeted genome editing approach to knock out the TaASN2 gene, which is primarily expressed in the grain and is responsible for asparagine synthesis. The technique involved introducing genes encoding the Cas9 nuclease, guide RNAs (gRNAs), and a marker gene into wheat embryos through particle bombardment. This process resulted in plants with modified TaASN2 genes, particularly affecting all six alleles (both alleles in each of wheat’s three genomes) (Raffan et al., 2021).
Initial glasshouse trials were promising, showing substantial reductions in free asparagine concentrations in the grain of plants carrying edits in all six TaASN2 alleles. One plant demonstrated more than a 90% reduction in asparagine levels. Even plants with modifications only in some genome copies showed lowered asparagine levels compared to wildtype plants (Raffan et al., 2021).
Following these promising results, the research progressed to field trials — Europe’s first field trial of gene-edited wheat — to assess performance under real-world conditions. The trials, conducted at Rothamsted Research farm in Harpenden, UK, included several edited lines along with control varieties. The field trials showed the low-asparagine trait was maintained under field conditions, with up to 50% reduction in asparagine levels compared to control varieties and corresponding reductions in acrylamide formation of up to 45% when the flour was baked (Raffan et al., 2023).
However, field trials also revealed that the gene-edited lines produced smaller grains, though with more seeds per plant, resulting in comparable overall yields to non-edited varieties. Researchers speculated that ‘perturbations of asparagine metabolism affected seed set, with the increased number of seeds in the GE lines being compensated for by reduced resource allocation to each seed‘, though they noted this required further investigation (Raffan et al., 2023).
Regulatory implications and foreign DNA challenges
The issue of foreign DNA removal has significant implications for the regulatory classification of these wheat varieties. Under various regulatory frameworks, including the UK’s 2023 Genetic Technology (Precision Breeding) Act, the presence or absence of foreign DNA can determine whether a genetically modified organism faces stringent GMO regulations or receives more lenient treatment as a ‘precision bred organism‘ (or New Breeding Techniques, NBTs) (Brock et al., 2025).
The UK’s Genetic Technology (Precision Breeding) Act enables any GM plant or animal that the developer declares could have arisen by traditional processes like breeding to evade the GMO regulations and be treated the same as a conventional organism. On the issue of foreign DNA, while the Act itself doesn’t specify requirements, guidance documents suggest that some foreign DNA may be permissible under certain circumstances.
In the European Union, the situation differs. While the EU has not traditionally defined GMOs based on the presence of foreign DNA, a deregulation proposal for New Genomic Techniques (NGTs) deregulation currently working its way through EU institutions may allow gene-edited plants without foreign DNA to be exempted from some or all regulatory safeguards that currently apply to GMOs (Kaur et al., 2024).
Natural alternatives to NGT wheat
An important question arising from these developments is whether the gene-edited (NGTs) approach is necessary or whether natural alternatives exist. Evidence suggests that there are indeed naturally low-asparagine wheat varieties already available.
GMWatch notes that ‘naturally low asparagine non-GM wheat varieties have long been available to farmers‘ (GMWatch, 2025). Research has identified natural genetic variation in the asparagine synthetase gene family in wheat, including a natural deletion of the TaASN-B2 gene in some varieties. Studies have shown that varieties lacking this gene tend to accumulate less free asparagine in their grain under normal growing conditions. For example, researchers have identified what they term a ‘natural ASN-B2 deletion‘ that could represent ‘a valuable genetic variant for wheat breeders to exploit in order to reduce free asparagine content in the grain‘ (Oddy et al., 2021). Moreover, the stability of this natural deletion phenotype under field conditions suggests that it could be a viable alternative to gene-edited varieties.
Additionally, evidence suggests that the asparagine content of wheat is significantly influenced by environmental factors and agronomic practices. In particular, sulphur deficiency has been identified as a major contributor to increased asparagine levels in wheat. Studies have demonstrated dramatic effects of sulphur availability on asparagine accumulation, with sulphur-deficient wheat showing substantially higher free asparagine concentrations (Muttucumaru et al., 2006).
Research has shown that grain from plots with no added sulphur had an average free asparagine content significantly higher than grain from wheat grown with adequate sulphur supply. Even modest sulphur deficiency can lead to marked increases in asparagine levels and consequently higher acrylamide formation when the grain is processed. This suggests that ensuring proper sulphur nutrition during wheat cultivation could be a simpler and more immediate approach to reducing acrylamide-forming potential in wheat-based foods (Elmore et al., 2008).
The acrylamide controversy
The significance of reducing acrylamide in foods has itself been subject to debate. While acrylamide is classified as a ‘probable human carcinogen‘ by the International Agency for Research on Cancer (IARC), the actual risk posed by dietary acrylamide remains uncertain.
Cancer Research UK states that ‘eating acrylamide in burnt toast and other burnt starchy foods is unlikely to increase the risk of cancer‘ and that ‘good quality studies of people have found no link between eating foods high in acrylamide and cancer‘. They further note that while animal studies have shown acrylamide to have cancer-causing effects, these studies used very high levels of the compound, far exceeding typical human dietary exposure (Cancer Research UK, 2024).
The World Cancer Research Fund similarly states that ‘studies on acrylamide and cancer in humans show that the amounts of acrylamide we consume probably doesn’t increase the risk of cancer significantly‘ (World Cancer Research Fund, 2025). This raises questions about the urgency and necessity of developing gene-edited wheat varieties specifically to address acrylamide concerns, especially given the availability of natural alternatives and agronomic approaches.
Financial considerations and public investment
The gene-edited (NGT) wheat project represents a significant investment of public resources. As Claire Robinson, GMWatch co-director, pointed out, the project ‘has already swallowed hundreds of thousands of pounds in taxpayer money at a time when ordinary people are struggling to pay for food and heating‘ (GMWatch, 2025). This raises questions about the allocation of research funding, particularly if simpler and less costly approaches to addressing acrylamide concerns exist.
The project has received funding from various sources, including the Biotechnology and Biological Sciences Research Council’s Super Follow-on Fund, which covered preparation for the field trial and its first year. Given the challenges encountered and the uncertain timeline for commercial development, there are legitimate concerns about the return on this public investment.
Future prospects and alternatives
While the Rothamsted NGT wheat project represents a significant scientific endeavour, the challenges encountered highlight the need for a multifaceted approach to reducing acrylamide in wheat-based foods. Recommendations include:
- Exploiting natural genetic variation. Breeding programmes could focus on selecting and developing wheat varieties with naturally lower asparagine accumulation, such as those with the TaASN-B2 deletion (Oddy et al., 2021);
- Improving agronomic practices. Ensuring adequate sulphur nutrition during wheat cultivation could significantly reduce asparagine accumulation and subsequent acrylamide formation. Research suggests that applying sulphur at rates of 20-40 kg per hectare can substantially reduce free asparagine concentrations in wheat grain (Halford et al., 2012);
- Food processing modifications. The food industry continues to develop processing techniques that minimize acrylamide formation during cooking, which could complement agricultural approaches (Raffan & Halford, 2019);
- Consumer education. Promoting awareness about cooking practices that reduce acrylamide formation, such as avoiding over-browning of starchy foods, represents a direct and immediate approach to reducing exposure.
Interim conclusions
The challenges facing Rothamsted Research’s gene-edited low-asparagine wheat highlight the complexity of developing genetically modified crops for commercial application. While the technical achievements in reducing asparagine levels and consequently acrylamide formation are noteworthy, the difficulties in removing foreign DNA and addressing germination issues raise questions about the viability of this approach.
A more comprehensive and diversified approach to the acrylamide issue appears more logical and appropriate, as well as able to provide immediate benefits for food safety without the higher costs of GMO – NGTs options. Taking into account the availability of naturally low-asparagine wheat varieties, the significant impact of agronomic factors such as sulphur nutrition, and the ongoing debate about the actual health risk posed by dietary acrylamide.
Dario Dongo
Cover art copyright © 2025 Dario Dongo (AI-assisted creation)
References
- Brock, N., Kaur, N., & Halford, N. G. (2025). Advances in genome editing in plants within an evolving regulatory landscape, with a focus on its application in wheat breeding. Journal of Plant Biochemistry and Biotechnology. https://doi.org/10.1007/s13562-025-00981-w
- Cancer Research UK. (2024, 18 December). Does burnt toast cause cancer? https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/cancer-myths-questions/does-burnt-toast-cause-cancer
- Elmore, J. S., Parker, J. K., Halford, N. G., Muttucumaru, N., & Mottram, D. S. (2008). Effects of plant sulfur nutrition on acrylamide and aroma compounds in cooked wheat. Journal of Agricultural and Food Chemistry, 56(15), 6173–6179. https://doi.org/10.1021/jf0730441
- GMWatch. (2025, 30 April). Gene-edited low acrylamide wheat hits roadblock. https://gmwatch.org/en/106-news/latest-news/20543
- Halford, N. G., Curtis, T. Y., & Muttucumaru, N. (2012). The acrylamide problem: a plant and agronomic science issue. Journal of Experimental Botany, 63(8), 2841–2851. https://doi.org/10.1093/jxb/ers01
- Kaur, N., Brock, N., Raffan, S., & Halford, N. G. (2024). Low asparagine wheat – Europe’s first field trial of genome edited wheat amid rapidly changing regulations on acrylamide in food and genome editing of crops. Breeding Science, 74(1), 37-46. https://doi.org/10.1270/jsbbs.23058
- Muttucumaru, N., Halford, N. G., Elmore, J. S., Dodson, A. T., Parry, M., Shewry, P. R., & Mottram, D. S. (2006). Formation of high levels of acrylamide during the processing of flour derived from sulfate-deprived wheat. Journal of Agricultural and Food Chemistry, 54(23), 8951-8955. https://doi.org/10.1021/jf0623081
- Oddy, J., Alarcón-Reverte, R., Wilkinson, M., Ravet, K., Raffan, S., Minter, A., Mead, A., Elmore, J. S., de Almeida, I. M., Cryer, N. C., Halford, N. G., & Pearce, S. (2021). Reduced free asparagine in wheat grain resulting from a natural deletion of TaASN-B2: investigating and exploiting diversity in the asparagine synthetase gene family to improve wheat quality. BMC Plant Biology, 21(1), 302. https://doi.org/10.1186/s12870-021-03058-7
- Raffan, S., & Halford, N. G. (2019). Acrylamide in food: Progress in and prospects for genetic and agronomic solutions. Annals of Applied Biology, 175(3), 259-281. https://doi.org/10.1111/aab.12536
- Raffan, S., Oddy, J., Mead, A., Barker, G., Curtis, T., Usher, S., Burt, C., & Halford, N. G. (2023). Field assessment of genome-edited, low asparagine wheat: Europe’s first CRISPR wheat field trial. Plant Biotechnology Journal, 21(6), 1097-1099. https://doi.org/10.1111/pbi.14026
- Raffan, S., Sparks, C., Huttly, A., Hyde, L., Martignago, D., Mead, A., Hanley, S. J., Wilkinson, P. A., Barker, G., Edwards, K. J., Curtis, T. Y., Usher, S., Kosik, O., & Halford, N. G. (2021). Wheat with greatly reduced accumulation of free asparagine in the grain, produced by CRISPR/Cas9 editing of asparagine synthetase gene TaASN2. Plant Biotechnology Journal, 19(8), 1602-1613. https://doi.org/10.1111/pbi.13573
- World Cancer Research Fund. (2025). Burnt food (acrylamide) and cancer. https://www.wcrf.org/preventing-cancer/topics/burnt-food-acrylamide-and-cancer/
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
