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The challenges of delivering genetically modified crops with nutritional enhancement traits


The potential for using genetic modification (GM) to enhance the nutritional composition of crops (for either direct human consumption or as animal feed) has been recognized since the dawn of the GM era, with such ‘output’ traits being considered as distinct, if not potentially superior, to ‘input’ traits such as herbicide tolerance and insect resistance. However, while input traits have successfully been used and now form the basis of GM agriculture, output trait GM crops are still lagging behind after 20 years. This is despite the demonstrable benefits that some nutritionally enhanced crops would bring and the proven value of GM technologies. This Review considers the present state of nutritional enhancement through GM, highlighting two high-profile examples of nutritional enhancement—Golden Rice and omega-3 fish oil crops—systematically evaluating the progress, problems and pitfalls associated with the development of these traits. This includes not just the underlying metabolic engineering, but also the requirements to demonstrate efficacy and field performance of the crops and consideration of regulatory, intellectual property and consumer acceptance issues.

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Journal peer review information: Nature Plants thanks Shan Lu, Mark Taylor and other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. 1.

    Bevan, M. W., Flavell, R. B. & Chilton, M. -D. A chimaeric antibiotic resistance gene as a selectable marker for plant cell transformation. Nature 304, 184–187 (1983).

  2. 2.

    Fraley, R. T. et al. Expression of bacterial genes in plant cells. Proc. Natl Acad. Sci. USA 80, 4803–4807 (1983).

  3. 3.

    Herrera-Estrella, L., Depicker, A., Van Montagu, M. & Schell, J. Expression of chimaeric genes transferred into plant cells using a Ti-plasmid-derived vector. Nature 303, 209 (1983).

  4. 4.

    Shah, D. M. & et al. Engineering herbicide tolerance in transgenic plants. Science 233, 478–481 (1986).

  5. 5.

    Vaeck, M. et al. Transgenic plants protected from insect attack. Nature 328, 33–37 (1987).

  6. 6.

    Global Status of Commercialized Biotech/GM Crops: 2016 (ISAAA, 2016).

  7. 7.

    Martin, C. & Li, J. Medicine is not health care, food is health care: plant metabolic engineering, diet and human health. New Phytol. 216, 699–719 (2017).

  8. 8.

    Enserink, M. Tough lessons from golden rice. Science 320, 468–471 (2008).

  9. 9.

    Burkhardt, P. K. et al. Transgenic rice (Oryza sativa) endosperm expressing daffodil (Narcissus pseudonarcissus) phytoene synthase accumulates phytoene, a key intermediate of provitamin A biosynthesis. Plant J. 11, 1071–1078 (1997).

  10. 10.

    Ye, X. et al. Engineering the provitamin A (beta-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm. Science 287, 303–305 (2000).

  11. 11.

    Al-Babili, S. & Beyer, P. Golden Rice—five years on the road—five years to go?. Trends Plant Sci. 10, 565–573 (2005).

  12. 12.

    Potrykus, I. Lessons from the ‘Humanitarian Golden Rice’ project: regulation prevents development of public good genetically engineered crop products. New Biotechnol. 27, 466–472 (2010).

  13. 13.

    Dubock, A. The present status of Golden Rice. J. Huazhong Agric. Univ. 33, 69–84 (2014).

  14. 14.

    Paine, J. A. et al. Improving the nutritional value of Golden Rice through increased pro-vitamin A content. Nat. Biotechnol. 23, 482–487 (2005).

  15. 15.

    Bollinedi, H. et al. Molecular and Functional characterization of GR2-R1 event based backcross derived lines of Golden Rice in the genetic background of a mega rice variety Swarna. PLoS ONE 12, e0169600 (2017).

  16. 16.

    Broun, P., Gettner, S. & Somerville, C. Genetic engineering of plant lipids. Annu Rev. Nutr. 19, 197–216 (1999).

  17. 17.

    Napier, J. A., Usher, S., Haslam, R. P., Ruiz-Lopez, N. & Sayanova, O. Transgenic plants as a sustainable, terrestrial source of fish oils. Eur. J. Lipid Sci. Technol. 1179, 1317–1324 (2015).

  18. 18.

    Domergue, F., Abbadi, A. & Heinz, E. Relief for fish stocks: oceanic fatty acids in transgenic oilseeds. Trends Plant Sci. 10, 112–116 (2005).

  19. 19.

    Petrie, J. R. et al. Metabolic engineering plant seeds with fish oil-like levels of DHA. PLoS ONE 7, e49165 (2012).

  20. 20.

    Usher, S., Haslam, R. P., Ruiz-Lopez, N., Sayanova, O. & Napier, J. A. Field trial evaluation of the accumulation of omega-3 long chain polyunsaturated fatty acids in transgenic Camelina sativa: Making fish oil substitutes in plants. Metab. Eng. Commun. 9, 93–98 (2015).

  21. 21.

    Napier, J. A., Olsen, R. E. & Tocher, D. R. Update on GM canola crops as novel sources of omega-3 fish oils. Plant Biotechnol. J. 17, 703–705 (2019).

  22. 22.

    Betancor, M. B. et al. A nutritionally-enhanced oil from transgenic Camelina sativa effectively replaces fish oil as a source of eicosapentaenoic acid for fish. Sci. Rep. 5, 8104 (2015).

  23. 23.

    Tejera, N. et al. A Transgenic Camelina sativa seed oil effectively replaces fish oil as a dietary source of eicosapentaenoic acid in mice. J. Nutr. 146, 227–235 (2016).

  24. 24.

    Lee, H. & Krimsky, S. The rrested development of Golden Rice: the scientific and social challenges of a transgenic biofortified crop. J. Soc. Sci. Stud. 4, 51–64 (2016).

  25. 25.

    Chi‐Ham, C. L. et al. An intellectual property sharing initiative in agricultural biotechnology: development of broadly accessible technologies for plant transformation. Plant Biotechnol. J. 10, 501–510 (2012).

  26. 26.

    Turrall, S. Evaluation of a public dialogue on Rothamsted Research working with industry (Rothamsted Research, 2014).

  27. 27.

    Stilgoe, J., Owen, R. & Macnaghten, P. Developing a framework for responsible innovation. Res. Policy 42, 1568–1580 (2013).

  28. 28.

    Stilgoe, J. A tale of two trials. Responsible Innovation (2015).

  29. 29.

    Martin, C. A role for plant science in underpinning the objective of global nutritional security? Ann. Bot. 24, 541–553 (2018).

  30. 30.

    Butelli, E. et al. Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors. Nat. Biotechnol. 26, 1301–1308 (2008).

  31. 31.

    Borrill, P., Connorton, J. M., Balk, J., Miller, A. J., Sanders, D. & Uauy, C. Biofortification of wheat grain with iron and zinc: integrating novel genomic resources and knowledge from model crops. Front. Plant Sci. 21, 53 (2014).

  32. 32.

    Naqvi, S. et al. Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways. Proc. Natl Acad. Sci. USA 106, 7762–7767 (2009).

  33. 33.

    Zhu, Q. et al. From Golden Rice to aSTARice: Bioengineering astaxanthin biosynthesis in rice endosperm. Mol. Plant 11, 1440–1448 (2018).

  34. 34.

    Polturak, G. et al. Engineered gray mold resistance, antioxidant capacity, and pigmentation in betalain-producing crops and ornamentals. Proc. Natl Acad. Sci. USA 114, 9062–9067 (2017).

  35. 35.

    Van Montagu, M. It Is a long way to GM agriculture. Annu. Rev. Plant Biol. 62, 1–23 (2011).

  36. 36.

    Alston, J. M., Andersen, M. A., James, J. S. & Pardey, P. G. Persistence Pays Vol. 34 (Springer, 2009).

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The authors thank BBSRC (UK) for financial support under Institute Strategic Programme Grants BBS/E/C/000I0420 and BBS/E/C/00005207.

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The authors declare no competing interests.

Correspondence to Johnathan A. Napier.

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Fig. 1: Schematic representation of timelines for conversion of idea into innovation in agriculture.