Truth: Cisgenesis shares many of the risks associated with transgenic genetic engineering
Cisgenesis is presented as safer and more publicly acceptable than transgenic genetic engineering, in which GM gene cassettes containing genes from unrelated organisms are introduced into the host organism’s genome.
However, in cisgenesis, the GM gene cassette will still contain DNA elements from other unrelated organisms like bacteria and viruses.
Cisgenesis is as mutagenic as transgenesis, and cisgenes can have the same disruptive effects as transgenes on the genome, gene expression, and a range of processes operating at the level of cells, tissues and the whole organism.
Thus cisgenic GMOs pose most of the same risks to health and the environment as transgenic GMOs. Experiments confirm that cisgenesis can result in important unanticipated changes to a plant.
Cisgenesis, sometimes called intragenesis, is a type of genetic engineering involving artificially transferring genes between organisms from the same species or between closely related organisms that could otherwise be conventionally bred. For example, a cisgenic GM potato engineered to resist blight was developed using a gene taken from a wild potato.1
Proponents claim that cisgenesis is safer than transgenesis, as purportedly it involves transfer of genetic material only between members of the same species and no foreign genes are introduced.23 Some scientists are calling for complete deregulation of cisgenic plants on the grounds that they carry no additional risks than naturally bred plants.4,5,6
Proponents also hope that cisgenics will overcome public resistance to GM. An article on the pro-GM website Biofortified, “Cisgenics – transgenics without the transgene”, bluntly states the public relations value of cisgenics: “The central theme is to placate the misinformed public opinion by using clever technologies to circumvent traditional unfounded criticisms of biotechnology.”7
However, cisgenesis still carries many of the risks associated with transgenic genetic engineering, for the following reasons.
[Header4] 1. No truly cisgenic GMOs exist
The word “cisgenic” (meaning “same descent”) implies that only genes within the genome of the same or closely related species are being manipulated. But no GMO has ever been or is likely to be created using only DNA from its own species. Some of the genetic information in the supposedly cisgenic organism does indeed come from close to home (the same species), which might suggest that there would be less likelihood of unpredictable outcomes.
However, although it is possible to isolate a gene from maize, for instance, and then put it back into maize, this will not be a purely cisgenic process. In order to put the gene back into maize, it is necessary to link it to other sequences, at least from bacteria, and possibly also from viruses, other organisms (potentially from different species), and even synthetic DNA.8,9
Therefore “cisgenic” gene transfer inevitably uses sequences foreign to the recipient organism. So “cisgenic” actually means “partly transgenic”. Unpredictability and risk from cross-species genetic information is not avoided.
For example, the cisgenic plants engineered by Rommens and colleagues (2004), who claim to have made “the first genetically engineered plants that contain only native DNA”, were produced using genetic modification mediated by the soil bacterium Agrobacterium tumefaciens – an organism from a different species.10
2. Cisgenic GMOs use the same mutagenic transformation techniques as transgenic GMOs
Cisgenic plants are created using the same highly mutagenic transformation techniques11 used to create other transgenic plants.12The process of inserting any fragment of DNA, whether cisgenic or transgenic, into an organism via the GM transformation process carries risks (see Myths 1.1, 1.2). Insertion takes place in an uncontrolled manner and results in at least one insertional mutation event within the DNA of the recipient organism. The insertional event will interrupt some sequence within the DNA of the organism and may interfere with any natural function that the interrupted DNA carries. For instance, if the insertion occurs in the middle of a gene, the gene’s function will likely be destroyed. As a result, the organism will lose the protein function that the gene encodes, with potential negative consequences for cellular and organ processes.
Although the main gene of the GM gene cassette may be cisgenic, the cassette will in all cases be inserted randomly into the genome of the recipient organism, that is, at a site other than its “natural” location. The location at which the cassette is inserted will influence the structure of the genome, which can influence the expression of genes in the whole region of the genome unpredictably. Furthermore, the regulatory sequences contained in the GM gene cassette can have unpredictable effects on the expression of genes located nearby.
In addition, cisgenesis, like transgenic genetic engineering, invariably involves the tissue culture process, which has wide-scale mutagenic effects on the plant host DNA.
Experimental evidence that cisgenesis can be as unpredictable as transgenesis
In arguing for less stringent regulatory oversight of cisgenic plants, Schouten and colleagues (2006) argue that unlike transgenic plant breeding, “cisgenesis does not add an extra trait” and that there is an “equivalence of products resulting from cisgenesis and traditional breeding including mutational breeding”.5
But such claims have been thrown into question by a series of experiments using the model plant Arabidopsis thaliana.13141516 These experiments assessed whether introduction of a cisgene introduced unanticipated trait changes. They also looked for differences between breeding methods by comparing plants where either genetic engineering or “conventional” breeding using chemical mutagenesis was used to introduce the identical trait into the identical genetic background. The trait deliberately introduced was herbicide resistance.
The results showed that trait introduction via a cisgene can result in plants that differ in unanticipated and dramatic ways from their conventionally bred counterparts. The differences observed would have important agronomic and ecological implications for commercial varieties.9
- Levels of outcrossing were higher in all GM lines carrying the cisgene as compared to the conventionally bred plants15
- When grown under field conditions, both the GM and conventional herbicide-resistant plants showed decreased total seed numbers as compared to the herbicide-sensitive wild-type parents. However, when nutrients were added to field-grown plants, only the transgenic plants still showed a fitness decrease.13,14
These results do not support the claims made by Schouten and colleagues.5 They show instead that a cisgene can introduce important unanticipated changes into a plant.
Cisgenesis is transgenesis by another name. Cisgenic GMOs pose most of the same risks as transgenic GMOs. The gene cassette developed to transfer a cisgene will also include DNA sequences from at least one other species, and therefore the gene cassette as a whole will be transgenic. In addition, cisgenesis involves tissue culture, a highly mutagenic process. The only difference between cisgenic and transgenic crops is the choice of organism from which the main gene of interest is taken. Experiments confirm that cisgenesis can result in important unanticipated changes to a plant.
- Jones JDG, Witek K, Verweij W, et al. Elevating crop disease resistance with cloned genes. Philos Trans R Soc B Biol Sci. 2014;369(1639):20130087. doi:10.1098/rstb.2013.0087.
- Rommens CM. Intragenic crop improvement: Combining the benefits of traditional breeding and genetic engineering. J Agric Food Chem. 2007;55:4281-8. doi:10.1021/jf0706631.
- Rommens CM, Haring MA, Swords K, Davies HV, Belknap WR. The intragenic approach as a new extension to traditional plant breeding. Trends Plant Sci. 2007;12:397-403. doi:10.1016/j.tplants.2007.08.001.
- Schouten HJ, Krens FA, Jacobsen E. Cisgenic plants are similar to traditionally bred plants. EMBO Rep. 2006;7(8):750-753. doi:10.1038/sj.embor.7400769.
- Schouten HJ, Krens FA, Jacobsen E. Do cisgenic plants warrant less stringent oversight? Nat Biotechnol. 2006;24(7):753-753. doi:10.1038/nbt0706-753.
- Viswanath V, Strauss SH. Modifying plant growth the cisgenic way. ISB News. 2010.
- Folta K. Cisgenics – transgenics without the transgene. Biofortified. 2010. Available at: http://www.biofortified.org/2010/09/cisgenics-transgenics-without-the-transgene/.
- Rommens CM. All-native DNA transformation: a new approach to plant genetic engineering. Trends Plant Sci. 2004;9(9):457-464. doi:10.1016/j.tplants.2004.07.001.
- Wilson A, Latham J. Cisgenic plants: Just Schouten from the hip? Indep Sci News. 2007. Available at: http://www.independentsciencenews.org/health/cisgenic-plants/.
- Rommens CM, Humara JM, Ye J, et al. Crop improvement through modification of the plant’s own genome. Plant Physiol. 2004;135(1):421-431. doi:10.1104/pp.104.040949.
- Schubert D, Williams D. “Cisgenic” as a product designation. Nat Biotechnol. 2006;24(11):1327-1329. doi:10.1038/nbt1106-1327.
- Wilson AK, Latham JR, Steinbrecher RA. Transformation-induced mutations in transgenic plants: Analysis and biosafety implications. Biotechnol Genet Eng Rev. 2006;23:209–238.
- Bergelson J, Purrington CB, Palm CJ, Lopez-Gutierrez JC. Costs of resistance: A test using transgenic Arabidopsis thaliana. Proc Biol Sci. 1996;263:1659-63. doi:10.1098/rspb.1996.0242.
- Purrington CB, Bergelson J. Fitness consequences of genetically engineered herbicide and antibiotic resistance in Arabidopsis thaliana. Genetics. 1997;145(3):807-814.
- Bergelson J, Purrington CB, Wichmann G. Promiscuity in transgenic plants. Nature. 1998;395:25. doi:10.1038/25626.
- Bergelson J, Purrington C. Factors affecting the spread of resistant Arabidopsis thaliana populations. In: Letourneau D, Elpern Burrows B, eds. Genetically Engineered Organisms. CRC Press; 2001:17-31. Available at: http://www.crcnetbase.com/doi/abs/10.1201/9781420042030.ch2.