4.2—Transgenes are safe, widespread in nature
GM Studies show that genes inserted into plants will cause no new risks
A standard test of every new transgenic plant variety is to check by protein analysis that the newly added protein—and only the intended protein—has been added to the profile of proteins produced by the growing plant. Biochemical methods for doing this are very well developed and are very powerful for revealing whether only one, or more than one new protein has been added. They are routinely applied to ensure that the newly added protein is present as intended. They are virtually the first step in checking that the transgenic plant performs as intended by the biotechnologists, and they provide information routinely required by the regulatory agencies. In this section of his book, Jeffrey Smith’s makes a number of speculations about possible presence of additional unexpected proteins in transgenic crops. He does not seem to be aware that the first step to finding out whether the expected protein is produced is to look for it directly, and that’s what scientists always do. Contrary to his guesswork, direct biochemical analysis of protein content of transgenic plants in the examples he mentions shows that they produce only the intended new protein.
Analysis of Peer-Reviewed Research:
1. Smith confuses DNA sequences with actual proteins produced in the GM plant. Genetic Roulette correctly cites evidence that shows that in the creation of herbicide tolerant sugar beets, a piece of inserted DNA was lost and the inserted DNA fused to sugar beet DNA. This DNA change happens in a way that theoretically could have generated a “fusion mRNA”—that is a piece of mRNA that contains the instructions for 69 percent of the inserted protein linked to enough beet DNA to encode 43 additional amino acids. Now there’s nothing to say that such a protein would cause harm since it would be made up of pieces of proteins that are safe—but the major problem is that Smith neglects to tell the reader that studies have shown that while mRNA corresponding to these sequences does exist, the protein is not present in cells (ANZFA 2001).
2. The transgenic Bt gene in Mon 810 yields the normal Bt digestion product when it is eaten. Genetic Roulette correctly notes that only 70 percent the gene encoding Mon810 was inserted in corn chromosomes. This shorter gene means that the maize produces a smaller Bt starting protein than initially seen in bacteria, but when eaten by the target insect both maize and bacterial Bt proteins are digested to give the identical active material. This production of shortened pre-digestion forms of Bt by Mon 810 corn is well characterized (Agbios n.d., Hernandez M and others 2003 ) and well known among insect biologists (Federici 2002, Romeis and others 2004), but Smith avoids letting the reader of Genetic Roulette know that the identical active product is formed. Mon 810 has been approved in more than 15 countries, including the very cautious EU. Regulators did not find this truncated protein of any concern. Mon810 has been carefully studied in animals, and also been widely planted around the world with no adverse effects observed (Betz and others 2000). It should come as no surprise that a fragment of a protein that can be eaten safely should also be safe. Cry1Ab has been fed to rats at levels 1 million times higher than we would find in the diet without any effects (other than to nourish the rats).
3. Mutations, deletions, and insertions accompany all plant breeding. It is, therefore, not surprising that local DNA rearrangements are sometimes seen in GM breeding. Recent studies have documented the massive disruptions in DNA that occur in conventional breeding (Batista and others 2008, Baudo and others 2006, Chen and 2006, Jiang and others 2004, Kashkush and others 2002, Leitch and Leitch 2008). For instance, plant scientists have identified more than 1000 hybrid genes in rice (Jiang and others 2004), and at least 3000 mutant varieties of crops created by radiation (that causes more genetic rearrangement that transgene insertion) are used by farmers (IAEA 2008). However, Smith is uninterested in informing the reader about such changes. Smith cites Mae Wan Ho’s claim that French and Belgian scientists have shown that the transgene in Syngenta Bt-176 (a variety that is no longer planted) is only 65 percent similar to the original Cry1Ab from which is was derived, and that the developer must have made a mistake because the product has 94 percent similarity to Cry1Ac. The claim is made by Mae Wan Ho with no reference, and there is apparently no scientific publication that we can judge. Regulators who approved the variety did not find inconsistencies in the nature of the inserted Cry sequences. (A similar claim of genetic instability is made by Smith in Section 2.6 of Genetic Roulette, and we discuss the issue further in analyzing those claims. See also the next section).
ANZFA (2001). Draft Risk Analysis Report, Application A378 Food derived from glyphosate-tolerant sugarbeet line 77 (GTSB77) www.foodstandards.gov.au/_srcfiles/A378FAR.pdf accessed Dec 23 2008
Batista R, Saibo N, Lourenço T, Oliveira MM (2008). Microarray analyses reveal that plant mutagenesis may induce more transcriptomic changes than transgene insertion. Proceedings of the National Academy of Sciences of the United States of America 105(9): 3640–3645. Radiation treatment causes more genetic change than does insertion of a transgene.
Baudo MM, Lyons R, Powers S, Pastori GM, Edwards KJ, Holdsworth MJ and Shewry PR. Transgenesis has less impact on the transcriptome of wheat grain than conventional breeding. Plant Biotechnol J. 2006 Jul;4(4):369-80.
Betz FS, Hammond BG, and Fuchs, RL (2000). Safety and advantages of Bacillus thuringiensis-protected plants to control insect pests. Regulatory Toxicology and Pharmacology 32:156-177. A key review which summarises the uses of Bt proteins to control insect pests in agriculture. Importantly provides key data substantiating the ~million-fold safety margins for Bt proteins
Belgian Biosafety Server (2006). Molecular characterisation of the genetic maps of commercial genetically modified plants. www.biosafety.be/gmcropff/EN/TP/MGC.html accessed Dec 26 2008. Provides description of DNA inserts in transgenic crops.
Chen ZJ and Ni Z (2006). Review article: Mechanisms of genome rearrangements and gene expression changes in plant polyploids. BioEssays 28:240-252. Newly created crosses between different plant species undergo numerous genetic changes.
Federici BA (2002). Case study: Bt crops—a novel mode of insect resistance. In: Atherton, K.(Ed.), Genetically Modified Crops: Assessing Safety. Taylor & Francis Group, London, pp. 164–200. Decribes the application of Bt proteins, including truncated versions such as Cry1Ab.
Hernández M, Pla M, Esteve T, Prat S, Puigdomènech P and Ferrando A. A specific real-time quantitative PCR detection system for event MON810 in maize YieldGard® based on the 3′-transgene integration sequence. Transgenic Research 12: 179–189. Describes the insert junction in Mon 810 that leads to a truncated Bt protein precursor.
IAEA (2008). Mutant plants can boost yields, resistance: IAEA conference (Vienna, Austria). Reports that some 3000 mutant plant varieties from 170 plant species are catalogued by the International Atomic Energy Agency. www.terradaily.com/2007/080812145530.x6uv6k68.htmlaccessed Dec 20 2008
Jiang N, Bao Z, Zhang X, Eddy SR, Wessler SR (2004). Pack-MULE transposable elements mediate gene evolution in plants. Nature 431, 569-573. Mobile DNAs in rice carry fragments of more than 1000 cellular genes.
Kashkush K, Feldman M, and Levy AA (2002). Gene loss, silencing and activation in a newly synthesised a wheat allotetraploid. Genetics 160:1651-1659. The history of safe use of genetics, with more information on the unexpected genetic changes that occurred during crop evolution. The re-enactment of the evolution of wheat to shows that when the two component grasses cross hybridised, many genes were silenced, activated, and some were lost.
Leitch AR and Leitch IJ (2008). Genome plasticity and the diversity of polyploid plants.Science 320:481-483 The success of flowering plant is partly attributable to their highly plastic genomes which can withstand large scale changes in structure over just a few generations.
Romeis J, Dutton A and Bigler F (2004) Bacillus thuringiensis toxin (Cry1Ab) has no direct effect on larvae of the green lacewing Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae). Journal of insect Physiology.50:175-183.CryIAb poses negligible risk for lacewing predator.
Transgenes may be altered during insertion
1. During insertion, the transgene may become truncated, rearranged, or interspersed with extraneous pieces of DNA
2. The transgene in MON810 was truncated; the protein is produces is derived from a combination of the transgene sequence and corn’s own DNA.
3. Proteins produced from altered transgenes may have unpredictable harmful effects.
Changes in DNA can occur during the insertion of genes