Team:Bielefeld-CeBiTec/Excellence in Another Area





Genetically Modified Organisms


Introduction

Genetically modified organisms (GMO) can be used in several sections thus they have high potential to be used in the future. While other countries like China or India already commercialised the usage of GM crops the EU still has strict regulations. According to scientists the usage of GMOs have no high risks because the genes are being modified directly instead of spontaneously. Nevertheless working and releasing GMOs still involve risks that can occur in the future. Therefore a lot of people are concerned regarding the topic of GMOs and their benefits. But before releasing a GMO several criterias and laws have to be taken into consideration as well as the costs that will emerge. Afterwards the problems regarding the future prospect have to be considered as well to prevent side effects. To minimize the likelihood of the occurrence of side effects the release has to be documented and monitored thus potential risks and prevention methods have to be clarified beforehand.


GMOs in general

To improve an organism, scientists often try to modify them on a molecular level and introduce new features. Organisms in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination are called GMOs (genetically modified organisms).[1] In addition to that, genes from one organism can be transferred into another organism by using DNA recombinant technology.[1]. According to the Cartagena Protocol on Biosafety to the Convention on Biological Diversity[2], any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology is also called GMO. The first genetically modified plants were produced by several research groups in 1983.[1] These plants were antibiotic resistant tobacco and petunias. Furthermore, scientist in China created a modified tobacco plant that has been commercialized in the early 1990.[1]

By using biotechnological methods to alter the DNA scientists have three main ways to modify genes in cells. The first one is to transfer DNA directly[1] for example by using electroporation or the biolistic transformation. In case of using the method of the electroporation scientist let the DNA, which is charged negatively, move down an electric potential gradient. Another method is to use bacterial vehicles to transfer DNA indirectly.[1] Worth considering is the bacteria Agrobacterium tumefaciens which uses a special plasmid (Ti-plasmid) to transfer modified DNA into the plant cell. According to Zhang et al. (2016) another method is the direct editing of genomic DNA by using the CRISPR-Cas9 system.[1] By using the Cas9 protein which induces a double stranded break the DNA is being repaired by two mechanisms in which the donor DNA can be integrated.[1]


Laws that should be considered

Despite the fact that the organisms being modified genetically a lot of laws have to be taken into consideration. Regarding GMOs in Germany the GenTG (Gene Technology Act) plays a main role. The purpose of this law is to protect the human health, human life, ethical values, the environment, animals and other plants from harmful impacts caused by GMOs.[3] Besides that the purpose of this law is also to prevent the emergence of these harmful impacts.[3] Without harming other crops the yield of genetically modified crops have to be ensured as well.[3] When releasing a GMO the GenTG also dictates that people who release GMOs have to need an approval from the higher federal authority.[3] Regarding Germany this higher federal authority is the BVL (Bundesamt für Verbraucherschutz und Lebensmittelsicherheit). Despite releasing GMOs which have been produced through certain methods the GenTG says that you do not need an approval. Firstly they mention the cell fusion with prokaryotic species that exchange genetic material through physiological process.[3] In addition to that the GenTG also mentions the cell fusion with eukaryotic species including the generation of hybridomas and the plant cell fusion.[3] Lastly people can release GMOs without an approval by using the method of self cloning of non-pathogenic or natural appearing organisms.[3]

GMOs in the EU are regulated by the Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC - Commission Declaration. It says that living organisms that have been released into the environment can breed themselves thus crossing land borders easily.[4] Therefore other members of the EU can get involved in this misery if the GMO has an impact on the environment. Before releasing any GMOs people in authority should accomplish an environmental impact assessment.[4] In addition to that, long term impacts should be considered as well as interactions with other GMOs. Antibiotic resistance should be considered as well regarding the environmental impact assessment.[4] Furthermore the release should be carried out by a step principle hence the regulations should be loosened after time. Another aspect is that the people of authority have to tell the government their intentions when releasing the GMO.

Regarding Asia GMO regulations are looser than in the EU. According to the ISAAA Report on Global Status of Biotech/GM Crops from 2007 the largest producers of GM products in Asia are China and India.[5] GM crops in China have to go through three phases of field trials before they are submitted to the Office of Agricultural Genetic Engineering Biosafety Administration (OAGEBA) for assessment.[6] Firstly they have to pass the pilot field testing followed by the environmental release testing and the pre production testing. China started in 1989 with insect-resistant genetically modified rice (IRGM)[6] transformation and reached a milestone in 2009 when the Chinese Ministry of Agriculture issued biosafety certificates for commercial production of two Bt-lines (Bacillus thuringiensis)[6]. Hence China made a great leap forward with the commercialization of these Bt-lines. In contrast to that India had a GM eggplant which was commercialized in October as well.[7] It was modified by Bacillus thuringiensis as well and has the name Bt brinjal.[7] Furthermore the release in India is governed by the Indian Environment Protection Act.[6] Talking about GMOs internationally the Cartagena Protocol on Biosafety to the Convention on Biological Diversity has to be taken into consideration. It is an international agreement on biosafety that seeks to protect biological diversity from the potential risks posed by GMO resulting from modern biotechnology.[8] It also states that products from new technologies must be based on the precautionary principle and allow developing nations to balance public health against economic benefits. As an example, countries can ban imports of GMO if they feel there is not enough scientific evidence that the product is safe.[8]


Criterias

Furthermore, there are certain criterias that have to be considered when talking about the release of a GMO in Germany. The BVL (Bundesamt für Verbraucherschutz und Lebensmittelsicherheit)[9] says that GMOs can be released without an approval when it has been approved by the EU. Besides that the person of authority gets the permission to release the GMO if it is not harmful for humans and/or the environment. While approving an approval the BVL has to check if the GMO is harmful for the environment, humans and/or other plants. The BVL verifies it through other scientific papers which provide information that can be used in the case of the approval. According to the BVL information regarding the GMOs have to be shown to the public. Citizens will be given the opportunity to inform themselves about this topic.


Costs

Moreover the release of a GMO contains costs considering the process of developing and releasing it. Firstly no comprehensive studies exist on the real costs of the entire process of developing and releasing one GM variety.[10] Hence two not-for-profit programs will be considered - one led by the CIP (International Potato Center) and the other one by Cornell University. These two institutions developed a light blate resistant (LBr) potato variety for release in one developing country.[10] Regarding this program CIP’s costs run to $1.6 million over eight years while Cornell’s costs run to $1.4 million over nine years.[10]


Besides that another survey found that the costs of discovery, development and authorization of a new plant biotechnology trait introduced in 2008-2012 was about $136 million.[11] In this survey six companies were surveyed and as a result sub category mean values were calculated.


Problems which can occur

While releasing a GMO the person of authority should always consider the risks that will occur. Therefore the risk assessment should be used as a regulation tool to decide about the release of a GMO.[12] A GMO can be injected into the ground thus long term impacts on biological communities and natural ecosystems can occur over the time. Moreover, by releasing a GMO it has to be guaranteed that the environment and the human health is secured when releasing GMOs. Therefore, the risks considered to the use of GMOs and ecological stability of GMOs should be clarified.

Another aspect is the genetic contamination or the genetic hybridization in which GMOs can interact with wild types or with sexual compatible relatives.[12] Wild types can develop a tolerance against several aspects through this interaction hence ecological relationships and behaviors could be changed by this.[12] Furthermore GMOs can compete with native species in which the quick growth of GMOs can lead to an advantage in terms of competition. GMOs can become invasive and grow in new habitats and as a consequence of this the ecosystem could be damaged.[12] Just the change of one species can have a big impact on a whole ecosystem.

Another important aspect is the horizontal gene transfer of recombinant genes onto other microorganisms. The horizontal gene transfer of one GMO into another organism can lead to a new trait that could cause damage in the future[12] As example the transfer of an antibiotic-resistance gene onto a pathogen could affect human health as well as the animal health.[12] Regarding the human health and pathogenicity of other organisms resulting from GMOs there is a higher chance of creating a new disease. Not only new diseases are created but the horizontal gene transfer could also integrate the introduced gene of the GMO into a yet unknown organism.[12] It is also stated that even with selection pressure it can take several generations to create an organism that can inherit the genes of a GMO.[12] This delay happens through changes in the organism itself or environmental conditions hence the appearance of several risks might come after a long time period.


GMO handling

The GMO handling in Germany has to be documented as required in the GenTAufzV (Gentechnik-Aufzeichnungsverordnung). It is stated that every work with GMOs has to be documented. Working with organisms with safety level S1 has only to be documented and not approved because the approval comes with higher safety levels.[13] Furthermore, working with GM plants has to be monitored to maintain safety for the uncontrolled spread and gene transfer. Therefore, safety features are a crucial component to achieve the safe release of GMOs into the environment.

Moreover, the aspect of biocontamination could be captured as well. In this case the team iGEM Marburg worked on chloroplasts to establish a cell free system. This system can be used as prototyping platforms for metabolic networks and genetic constructs. Their system can be used to provide safety in terms of GMOs. By introducing the gene into the chloroplasts, the only genetically modified component is the chloroplasts itself. Therefore, parts of GMO or their transgene products do not contain the introduced genes which can secure biocontamination.

The standard way of preventing the spread of GMOs and thus accomplish a safe release, is to sterilize the GMO, making reproduction impossible.


Outreach

Regarding genetic engineering in food and agriculture, people who support genetic engineering for food and agriculture say that farm-workers' exposure to pesticides can be reduced.[14] Additionally the agriculture yields and the amount of vitamins are increased by using genetic engineering. Considering the golden rice for example the nutrition was being increased by adding vitamins.[14] On the other hand people who are against this topic mention the toxicity and/or allergens associated with GMOs as long-term risks.[14]

Statements for using GMOs in detail are that ingredients will be checked harder than usually. For example China and the US already sell genetically modified products as food.[15] Besides that genetic modifications are controllable because of targeted modification of the genes by creating mutations via chemicals or irradiation.[15] Regarding the outcrossing it is stated that it should be nearly impossible if there are precautions regarding this topic. Furthermore, GM plants are more sustainable than normal plants. The tolerance against pests could be increased while reducing the use of sprays. Scientists also work on species that should be resistant against environmental changes.[15]

Recent developments in utilization of genome editing tools in plants breeding include zinc finger nucleases (ZNF), transcription activator-like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR).[16] Genome editing can be used for the introduction of various valuable traits such as increased stress tolerance or disease resistance or improvement of quality and yields.[16] By using CRISPR-Cas based methods for crop improvement, scientists already developed several modified plant species (herbicide-resistant rice, ß-carotene-rich bananas, soybean with improved oil quality etc.).[16] Regarding the usage of genome editing in the plant sector opportunities and challenges will occur. An advantage is that genome editing is more precise and efficient than random mutagenesis.[16] It is also estimated that genome editing can shorten plant breeding programs considerably by up to four to six years depending on the crop.[16] Furthermore plant breeding companies have embraced the usage of genome editing for the production of enhanced crop plants such as sulfonyl herbicide-tolerant canola, cyst nematode-resistant rice or mildew-resistant wheat.[16] With the usage of gene editing plant breeders have the flexibility of introducing minor genetic changes in target genes comparable to induced random mutagenesis but without introducing additional random mutations elsewhere in the genome.[16]

A challenge may be that many plant traits are polygenic hence being influenced by multiple genes.[16] Therefore multiple edits are required to alter the phenotype of a crop which is possible by using multiplex CRISPR technology.[16] With this technique edits at multiple sites in the genome is achievable. Additionally, a challenge is also that strict safety measures are needed. Rules should be declared so the competitiveness with other companies with less strict GMO regulations is secured.[16]


Plants for detection

GMOs can be used in several sections. Regarding GM plants these plants can be used to detect other substances. As examples for detection plants the Danish Working Environment Authority approved application for testing of genetically modified A. thaliana.[17] The company developed this plant to detect explosives in soil like landmines. The same company gets permission from the Serbian authorities as well to plant transgenic tobacco for the detection of explosives.[18] This plant was used for detection of explosives from land mines and it changed its colour after growth in soil with explosives.[18] Another plant is the modified spinach which serves as a sensor that can detect explosives in the ground.[19] Its roots can identify nitro aromatics which appear in land mines and explosives. Integrated carbon nanotubes in the leaves send out a signal that can be detected by infrared cameras.[19] This plant has a future potential because it could be used to detect pollution and/or other environmental problems.

References



[1] Zhang C. et al., Genetically modified foods: A critical review of their promise and problems (2016)

[2] Sendashonga C. & Hill R., The Cartagena Protocol on Biosafety: Interaction between the Convention on Biological Diversity and the World Organisation for Animal Health (2005)

[3] https://www.gesetze-im-internet.de/gentg/BJNR110800990.html (access 02.10.21)

[4] https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex%3A32001L0018 (access 02.10.21)

[5] James C. et al., ISAAA Report on Global Status of Biotech/GM Crops, International Service for the Acquisition of Agri-biotech Applications (ISAAA) (2007)

[6] Chen M. et al., Insect-Resistant Genetically Modified Rice in China: From Research to Commercialization (2011)

[7] http://news.bbc.co.uk/2/hi/south_asia/8506047.stm (access 03.10.21)

[8] Secretariat of the Convention on Biological Diversity, Cartagena Protocol on Biosafety to the Convention on Biologial Diversity (2000)

[9] https://www.bvl.bund.de/DE/Arbeitsbereiche/06_Gentechnik/01_Aufgaben/02_ZustaendigkeitenEinzelneBereiche/02_Freisetzung/gentechnik_freisetzung_node.html (access 03.10.21)

[10] Schiek B. et al., Demystification of GM crop costs: Releasing late blight resistant potato varieties as public goods in developing countries (2016)

[11] McDougall P., The cost and time involved in the discovery, development and authorisation of a new plant biotechnology derived trait (2011)

[12] Prakash D. et al., Risks and Precautions of Genetically Modified Organisms (2011)

[13] https://www.gesetze-im-internet.de/gentaufzv/GenTAufzV.pdf (access 03.10.2021)

[14] https://research.ncsu.edu/ges/igert/student-research/island-mice-conserving-island-biodiversity/island-mice-what-is-the-future/ (access 04.10.2021)

[15] https://www.focus.de/wissen/technik/gentechnik/wie-gefaehrlich-ist-gruene-gentechnik-eu-will-gvo-richtlinien-lockern_id_2867041.html (access 04.10.2021)

[16] van der Berg J. et al., Future-Proofing EU Legislation for Genome-Edited Plants: Dutch Stakeholders' View on Possible Ways Forward (2021)

[17] The Danish Working Environment Authority, Aresa receives GMO approval (2007)

[18] https://www.dgap.de/dgap/News/adhoc/aresa-has-achieved-get-permission-from-the-serbian-authorities-plant-transgenic-tobacco-for-the-detection-explosives/?newsID=208003 (access 4.10.2021)

[19] https://de.euronews.com/green/2021/02/07/achtung-dieser-spinat-verschickt-emails-und-warnt-vor-sprengstoff-gefahr (access 6.10.2021)