Crop Genetic Engineering, Warts and All

This is a paper I wrote that was published by PBGworks October 26, 2012:

Crop genetic engineering is a powerful technology that is helping scientists reveal how genes and genomes function. It could also be used to solve important global agricultural problems. However, in addition to moving genes, after precise manipulation in laboratories, from one organism to another, crop genetic engineering as it is currently practiced can produce many unexpected, AKA pleiotropic, effects. As a scientist, I take to heart the words of Albert Einstein who said “The right to search for the truth implies also a duty; one must not conceal any part of what one has recognized to be the truth” [1]. Only by considering all of what is known about the science underlying crop genetic engineering, warts and all, can we as a society decide how to most safely, effectively and sustainably utilize this powerful technology.

Both of the current methods for delivering foreign genes into crop plants often result in substantial disruption of host plant DNA. The Agrobacterium-mediated method causes high rates of insertional mutagenesis; “in the plant species most studied (A. thaliana and rice), approximately 27%-63% of T-DNA insertions disrupt known gene sequences” [2 and references therein]. Research scientists have utilized the high rates of T-DNA insertional mutagenesis to mutate, tag and clone plant genes [3, 4]. And although very few analyses of the insertion sites of foreign genes in plants transformed using the particle bombardment method have been published, those available indicate that extremely complex insertions are the norm; for example, in addition to the inserted enoylpyruvate shikimate synthase (EPSPS) transgene in one commercialized Roundup Ready soybean event, fragments of EPSPS transgenes (2), plant DNA and “unidentified” DNA, as well as evidence of altered flanking soybean DNA, were also found [5]. Unintended gene disruptions or gene activations are also a problem in human gene therapy as retroviruses, like Agrobacterium tumefaciens [6 and references therein], preferentially insert DNA into regions of host genomes with active protein-coding genes [7]; unintended mutations in host genes could adversely affect both GE food products [a hypothesis that should be tested in cases like 8-10] and human patients treated for X-linked severe combined immunodeficiency disease using retroviral vectors [7]. Consequently, efforts are underway to establish technologies for site-specifically inserting transgenes into both plants [11, 12] and animals [7].

Other unintended effects can be and have been associated with the foreign DNA inserted into GE crop plants. The Bt protein in StarLink corn was described by the EPA as “potentially allergenic” (whereas other Bt proteins had not been) and therefore “directed to [only] domestic animal feed or to industrial uses” and yet still unintentionally entered the human food supply [13].  In addition to the genes meant for transfer into plants, “vector backbone” sequences can also be unintentionally inserted into GE plants [14]; in one case, a GE corn crop unintentionally containing a “vector backbone” gene encoding an ampicillin-resistance protein was unintentionally introduced into commerce [15]. Other GE crops with transgenes that were not inserted [16] or expressed [17] as intended have also been commercialized.

In addition to unintended effects, there are problems associated with GE crop plants that might be classified as human errors. For example, 20 years ago environmental scientists warned us that, just as over-use of antibiotics led to antibiotic-resistant bacteria, developing GE crops that are resistant to pesticides would result in “super-weeds” or “super-insects” resistant to those pesticides and that is indeed what has come to pass. “Super” versions of pigweed, horseweed and giant ragweed that are glyphosate-resistant [18 and e.g. 19] (glyphosate being the active ingredient in products like Roundup) have now infested millions of acres in at least 22 U.S. states and are also posing problems in agricultural areas of Brazil, Australia and China. “Super-insects” resistant to the insecticides produced in other GE crops are also starting to show up on U.S. farms [20]. Evidence of harm to black swallowtail butterfly larvae caused by exposure to pollen from a GE corn variety expressing especially high levels of insecticide specifically in pollen, a plant tissue bound to “escape” corn fields and therefore potentially affect non-target insects, has also been reported [21].

In light of the potential for unintended effects and human errors, and the fact that the products of this powerful technology are self-replicating, it should be required that each GE crop be evaluated by U.S. regulators on a case-by-case basis prior to commercial release. However, the current “coordinated framework” for regulating GE crops using three different U.S. regulatory agencies can let products of the technology slip through the cracks. Only GE plants that produce their own pesticides need be regulated by EPA [22]. Only GE products produced using organisms (or parts thereof) on USDA’s “plant pest” list need be regulated by that agency [23]. And the FDA, with only a couple of exceptions, recommends that developers consult with them about their GE food products (and claims that developers have routinely done so) but does not require them to [22].  It is therefore currently possible to design a GE crop that would not require pre-market regulation by any U.S. agency.

The current situation I’ve “recognized to be the truth” [1], i.e. commercialization of products of a powerful technology with the potential for myriad unintended side effects yet with inadequate regulation and research [24, 25], is not conducive to inspiring public confidence in crop genetic engineering. The fact that GE food products are also not labeled in the U.S. only makes the situation worse. If the potential of this technology for solving important global agricultural problems is to be realized, it must be utilized more carefully and transparently; pre-market regulation and labeling should be mandatory.

It is worth noting that the world’s first GE whole food, Calgene Inc.’s Flavr SavrTM tomato, was labeled and also well received by the public. There were many reasons why the Flavr Savr tomato eventually flopped (one being that the company “tried to make [the tomato business] too big, too fast” [26]) but public outcry at the fact that it was genetically engineered was not one of them. Almost without exception during the course of its brief commercial run, demand for the Flavr Savr tomato outdistanced supplies [27-31]. Also, a clearly labeled GE tomato paste developed by Zeneca Plant Sciences initially outsold conventional tomato paste in the U.K. by 30% [32]; more than 1.8 million cans of that GE tomato paste were sold in Sainsbury’s and Safeway stores from 1996 through mid-1999. Therefore, based on these historical examples, labels on food products containing genetically engineered ingredients need not serve as “scarlet letters.”

I believe it is in the best interest of the agricultural biotechnology industry to try to (re)establish public confidence in the powerful technology of crop genetic engineering. Being transparent is one way toward accomplishing that. I therefore support Prop 37, the initiative on this November’s California ballot that requires labeling of GE foods.

And science aside, members of any capitalist, democratic society should have the right to know what they are buying in grocery stores to feed themselves and their families.

Belinda Martineau, Ph.D., earned her bachelor’s degree in biology from Harvard College and her doctorate in genetics from U.C. Berkeley. Prior to joining Calgene, Inc. in 1988 she was a post-doctoral fellow at the University of Chicago. She is the author of First Fruit: The Creation of the Flavr SavrTM Tomato and the Birth of Biotech Food and a Principal Editor at U.C. Davis.

References

  1. Panel on Scientific Responsibility and the Conduct of Research, National Academy of Sciences, National Academy of Engineering, Institute of Medicine (1992) Responsible Science, Volume I: Ensuring the Integrity of the Research. The National Academy Press, Washington, D.C., p iii.
  2. Latham JR, Wilson AK, Steinbrecher RA (2006) The mutational consequences of plant transformation. J Biomed and Biotech 2006: 1-7.
  3. Walbot V (1992) Strategies for mutagenesis and gene cloning using transposon tagging and T-DNA insertional mutagenesis. Annu Rev Plant Physiol Plant Mol Biol 43: 49-82.
  4. Alongso JM, Stepanova AN, Leisse TJ et al. (2003) Genome-wide insertional mutagenesis of Arabidopsis thaliana. Science 301: 653-656.
  5. Windels P, Taverniers I, Depicker A et al. (2001) Characterisation of the Roundup Ready soybean insert. Eur Food Res Tech 213: 107-112.
  6. Zambryski PC (1992) Chronicles from the Agrobacterium-plant cell DNA transfer story. Annu Rev Plant Physiol Plant Mol Biol 43: 465-490.
  7. Michel G, Yu Y, Chang T, Yee J-K (2010) Site-specific gene insertion mediated by a Cre-loxP-carrying lentiviral vector. Molec Therapy 18: 1814-1821.
  8. Ewen SWB, Pusztai A (1999) Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. The Lancet 354: 1353-1354.
  9. de Vendomois JS, Roullier F, Cellier D, Seralini G-E (2009) A comparison of the effects of three GM corn varieties on mammalian health. Int J Biol Sci 5: 706-726.
  10. Seralini G-E, Clair E, Mesnage R et al. (2012) Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food Chem Toxicol 50: 4221-4231.
  11. Lyznik LA, Gordon-Kamm W, Gao H, Scelonge C (2007) Application of site-specific recombination systems for targeted modification of plant genomes. Transgenic Plant J 1: 1-9.
  12. Li Z, Xing A, Moon BP et al. (2009) Site-specific integration of transgenes in soybean via recombinase-mediated DNA cassette exchange. Plant Physiol 151: 1087-1095.
  13. EPA website: http://www.epa.gov/oppbppd1/biopesticides/pips/starlink_corn.htm#allergenicity (accessed 23 Oct 2010).
  14.  Martineau B, Voelker TA, Sanders RA (1994) On defining T-DNA. Plant Cell 6: 1032-1033.
  15. FDA website: http://www.fda.gov/Food/Biotechnology/Submissions/ucm121422.htm (accessed 23 Oct 2010).
  16. Monsanto website: http://www.monsanto.com/products/Documents/safety-summaries/mon89034_pss.pdf (accessed 23 Oct 2010).
  17. Monsanto website: http://www.monsanto.com/products/Documents/safety-summaries/corn_pss_NK603.pdf (accessed 23 Oct 2010).
  18. Neuman W and Pollack A (2010) Farmers cope with Roundup-resistant weeds. The New York Times, May 3: http://www.nytimes.com/2010/05/04/business/energy-environment/04weed.html?pagewanted=all&_r=0 (accessed 23 October 2012).
  19. Powles SB (2010) Gene amplification delivers glyphosate-resistant weed evolution. Proc Natl Acad Sci USA 107: 955-956.
  20. Gassmann AJ, Petzold-Maxwell JL, Keweshan RS, Dunbar MW (2011) Field-evolved resistance to Bt maize by Western corn rootworm. PLoS ONE 6: e22629.
  21. Zangerl AR, McKenna D, Wraight CL et al. (2001) Effects of exposure to event 176 Bacillus thuringiensis corn pollen on monarch and black swallowtail caterpillars under field conditions. Proc Natl Acad Sci USA 98: 11908-11912.
  22. FDA website: http://www.fda.gov/Food/Biotechnology/default.htm (accessed 23 Oct 2012).
  23. Waltz E (2011) GE grass eludes outmoded USDA oversight. Nature Biotech 29: 772-773.
  24. EPA website: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2008-0836-0043;oldLink=false (accessed 23 Oct 2012).
  25. Pollack A (2009) Crop scientists say biotechnology companies are thwarting research. The New York Times, February 19:  http://www.nytimes.com/2009/02/20/business/20crop.html (accessed 23 Oct 2012).
  26. Groves M (1996) Monsanto to raise stake in Calgene and replace CEO. The Los Angeles Times, August 1.
  27. Jenkins N (1994) Retail revolution or produce footnote? Produce Merchandising December.
  28. Anonymous (1994) At last a tomato with home-grown garden flavor. Sacramento Bee, November 26.
  29. Anonymous (1995) Calgene hit with setback. Sacramento Bee, May 17.
  30. Black J (1995) Genetically altered tomatoes ripe for tossing in Seattle salads. Seattle Times, May 17.
  31. MacPherson K (1995) Calgene Flavr Savr beats the standard varieties in a blind taste test. Star-Ledger (Newark, NJ), May 17.
  32. Stecklow S (1999) “Genetically Modified” on the label means…well, it’s hard to say. Wall Street Journal, October 26.
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3 Responses to Crop Genetic Engineering, Warts and All

  1. Pingback: Hyper-propagandizing crop genetic engineering in The New Yorker? | Biotech Salon

  2. Pingback: Pew Research Center Finds “Americans have Limited Trust in Scientists Connected with Genetically Modified Foods” | Biotech Salon

  3. Pingback: Scientific Uncertainty and Professional Ethics as Related to GMOs | Biotech Salon

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