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Transgenic technology illustrates the process of transferring foreign deoxyribonucleic acid (DNA) material into the genome of a host organism.[1] The foreign genetic material can be composed of DNA from a different species or recombinant genes of the same species, that had been artificially engineered in the laboratory. The term 'transgenic species' share interchangeable definitions with genetically modified organisms (GMO).[2] The transformation or transfection of genetic material in the host organism manipulates its biological functions on a molecular level, enabling precise modification of amino acid production and protein synthesis.[3] The technology’s relatively recent discovery has allowed for its usage in a wide range of industries, increasing production efficiency as well as facilitating biomedical research.[4] Unsystematic utilization in certain regions has given rise to controversial debates, advocating for the establishment of stringent legislations by local and international regulatory institutions to monitor potential ethical concerns.[5]

History

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Before the development of transgenic technology, desired characteristics were obtained by selectively breeding animals or plants to yield offsprings. However, selective breeding had limitations of simply inducing offspring that express certain traits,[6] rather than manipulating genetic profiles of various organisms using laboratory techniques. Development of transgenic technology in the late 1900s allowed Cohen to transform an E.Coli bacterium with plasmid DNA, discovering the first transgenic organism in 1973.[7] Thereafter in 1981, Palmiter showed success in inserting a cloned growth hormone gene into a mouse,[8] discovering the first transgenic animal expressing the transgene. Continuous scientific research led to cloned animals, such as Dolly the Sheep created in 1996.[9]

Methods

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Transgenic technology can be performed using various approaches with distinct techniques and biological samples.

Transgene construction

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The DNA of interest is isolated by lysis to obtain the target gene. If required, multiple target genes are combined by recombination and inserted into a vector using ligase.[10] The accuracy of DNA lysis and gene ligation are controlled by the physical compartments of the transgene.[11]

Transgene transfer

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Following its construction, the transgene is transferred to the recipient through any of the following methods:[12]

Figure 1. Methods of Transgene Transfer
Method Description
DNA Microinjection The gene-of-interest is directly inserted into the pronucleus of a zygote, using microinjection.

These cells are cultured in vitro until they grow into embryonic cells, which are then transferred into a female recipient.

Retrovirus-mediated gene transfer The Retrovirus vector containing the gene-of-interest transfers and reverse-transcribes its genetic information (RNA) to integrate with the genome of the host cell.

This host cell containing a retrovirus with the transgene is called a ‘chimera’.

Sperm-mediated gene transfer During fertilization, a linker protein is bound to the sperm to transfer new genetic information into the zygote.
Embryonic stem cell-mediated gene transfer Transgene is introduced to totipotent stem cells that have been isolated from blastocysts forming the inner layer of embryos.

These modified cells are implanted back to the embryo.

Nuclear transfusion The nucleus removed from a donor cell is transplanted into a recipient cell.

The recipient grows with cells resembling the donor’s. Dolly the Sheep was cloned using this method.

Applications

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Transgenic technology is being actively incorporated for application in a variety of industries.

Animal model for research

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Transgenic technology can be applied in order to genetically modify animals for scientific research.[13] These models such as knockout mice and oncomice are commonly used for studying disease etiology as well as the function of recently discovered genes and proteins.[14] They also serve as models for testing safety and efficacy of specific genetic modifications before testing it in humans. However, taking advantage of animals and putting their lives at risk[15] still remains controversial. Despite all research labs being required to follow ethical guidelines provided by regulatory institutions, in some cases, their compliance or honest reporting can be questioned.[16]

Clinical application

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There exists a range of clinical applications where transgenic technology is used in therapeutic or preventative approaches for targeting disease.

Gene therapy

A large proportion of diseases arise from defective alterations of genes, or mutations. Accordingly, utilization of transgenic technology can allow for the conductance of therapeutic measures to transfer healthy genes to patients with defective genes.[17] This clinical method targeting genetic disorders is referred to as gene therapy.

Production of pharmaceutical products

Through utilization of transgenic technology, animals can be transduced to produce pharmaceutical products in large quantities. The first application was carried out by transferring a recombinant gene coding for human anticoagulant antithrombin ATryn to goats,[14] which resulted in its production in goat milk.

Development of resistance to diseases

Transgenic technology can produce immunoglobulins consisting of a variable domain derived from one species and a constant domain derived from another, together called a chimeric antibody. This can induce expression of specific immunoglobulins in desired species to decrease its susceptibility or increase resistance to foreign agents and disease.[18]

Xenotransplantation

Usage of transgenic technology can enable the production of cells, tissues or organs by animals that closely resemble those in humans. Humans recipients in need of xenografts can receive transplantation from these animals, though donor rejection is a concern still in study.[19]

Agricultural Application

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Main article: Genetically modified crops

Agricultural application of transgenic technology had underwent practice over multiple generations in human history, becoming increasingly more complex and developed since traditional methods such as cross-breeding.

First generation - There exists a wide range of agricultural applications of transgenic technology. The first generation of transgenically modified crops aimed to establish agricultural resistance to environmental and chemical factors that affect crop production, such as herbicides.[20]

Example (case study): Herbicide-resistant crops

Glyphosate is a herbicide used for commercial weed control in farming crops such as soybean and corn since its first registration by the U.S. Environmental Protection Agency in 1974.[21] Ever since its first appearance in agricultural practices, its use became prevalent in the U.S. farmland.[22] Transgenic technology enables for bacteria-mediated biosynthesis of glyphosate-tolerant EPSP Synthase enzyme or production of glyphosate-degrading enzyme in crops, inducing herbicide tolerance.[23]

Second generation - Crops that were put under transgenic modification in the second generation, were geared towards quality and nutrient profile improvement.

Golden rice compared to white rice

Example (case study): Golden Rice - In the late 1990s towards the early 2000s, research commenced on transgenically modifying rice to contain beta carotene A (provitamin A), that is an essential nutrient lacking in rice.[24] The project aims to combat vitamin A deficiency, a public health concern that predominantly affects rice-dependent populations in Southeast Asia with lack of access to a variety of foods high in vitamin A.[25] The World Health Organization projects an estimate of 250 million preschool children who suffer from vitamin A deficiency, from which 2.7 million die from severe clinical consequences. If left untreated, vitamin A deficiency can incur acute damages to the optical system such as eye dryness and even blindness.[26] The Golden Rice project aims to reduce preventable blindness and death from vitamin A deficiency.

Third generation - Modern approaches in applying transgenic technology in agriculture involves modifying crops for use other than consumption. Pharmaceutical agents, biofuels and bioremediation are some fields of development where agricultural products are cultivated with transgenic modifications, to serve the needs of industrial markets.

Example (case study): Biopharmaceuticals created from plants - Transgenic technology enables for production of a variety of hormones, proteins, antibodies and vaccines for clinical usage.[27] For example, using transgenic methods such as nuclear or chloroplast transformation, edible vaccines can be produced from transgenic plants. Tissues from model transgenic plants, especially tomato, potato and tobacco are used for transgenic modification, to extract vaccines and antibodies for treating diseases such as the Hepatitis B virus, Human Immunodeficiency Virus (HIV) and malaria.[28]

Industrial Application

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Corn harvested for use in production of ethanol

Transgenic technology is growing more prevalent in use of industrial processes, to increase yield and efficiency of manufacturing and production. A number of industries other than those aforementioned, incorporate transgenic technology in serving such purpose. Examples of these industries include cotton, corn, soybean and goats.[29] 80% of all cotton grown worldwide is said to be transgenically modified species that were engineered to be insect and herbicide tolerant.[30] Corn and soybean, other than for consumption, are being actively applied in generation of biofuel: ethanol from corn and soybean oil as a replacement for formaldehyde and petroleum. An interesting case is that of goat milk, where spider’s silk-spinning genes were successfully transferred into the goat genome, enabling goats to produce milk with silk protein.[31] Harvesting silk from goat’s milk can be applied into a number of industrial uses, due to its strength, elasticity and versatility. Spider silk can be manufactured into producing clinical instruments such as artificial eye structures, artificial tendons and ligaments, as well as serve other purposes like creating bulletproof vests and airbag for vehicles.

Regulation

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See also: Regulation of genetic engineering

Intra-governmental and inter-governmental regulatory approaches exist to monitor the administration of transgenic species, or genetically modified organisms.[32] The first regulatory measures at regulating transgenic species was first put under construction during the Asilomar conference in 1975. The Asilomar conference consisted of a gathering between 140 biologists, physicists, lawyers and healthcare professionals at Asilomar state beach to interchange views towards potential risks, hazards and regulatory boundaries regarding bioengineered species, including those that involve gene transfer. Analysis on such risks was conducted on various biotechnology experiments on application of recombinant DNA. Recommendations were issued to form the foundational agreements on regulations of transgenic technology for the global scientific community.[33] Following the Asilomar conference, The Cartagena Protocol on Biosafety was established on 29 January 2000 with signatures from 157 countries, an agreement from which countries have taken different degrees of further regulation.

In order to respond to increases in pursuit of applying transgenic technology by various private and public institutions conducting biological research, the Nagoya-Kuala Lumpur Supplementary Protocol was adopted on 15 October 2010. The Supplementary Protocol addressed the call for attention in establishing additional laws and damage response procedures for the risks of transgenic technology, especially those regarding threats to biodiversity, pollution, health and safety.[34]

Figure2. Regulatory Agencies by major Governing Bodies
Governing body Regulatory agencies Notes
The United States[35] USDA, FDA and EPA Not a party to the Cartagena Protocol on Biosafety.

FDA regulates all transgenically modified food, animals, drugs and other biological products by setting boundaries on their development and consumption.

EPA regulates pesticides and microorganisms to which transgenic technology is applied.

USDA adopts protocols to agricultural products produced from transgenic technology.

European Union[36] European Commission, European Food Safety Authority (EFSA) European Commission grants authorizations for transgenic organisms and foods imported into the EU.

EFSA regulates conducts risk assessments of transgenic products at the EU level.

Cultivation of transgenic organisms, agriculture and other biological products are regulated by EU state members.

International Protocols Cartagena Protocol, Nagoya-Kuala Lumpur Supplementary Protocol

Controversy

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See also: Genetically modified food controversies

There exists major areas of controversy regarding transgenic species and their application. A particular area of focus is the unprecedented risks associated with transgenically modified agricultural goods, including crop and animal products.[37] Health and safety concerns regarding consumption of transgenically modified products raise concerns on potential allergic reactions and health risks that are yet to be identified as confirmed cases of adverse effects.[38] Environmental effects, such as loss of biodiversity, occurrence of herbicide or pesticide resistant plant species and sterilization of certain animal and plant species are also controversial in assessing the safety and efficacy of transgenic technology.[39]

Social and religious issues, on humans ‘playing god’, are also raised with increased awareness in particular geographical regions. There exists religious and social groups with such heightened sense of fear and resistance to the development of transgenic technology. Such fear arises from the idea that human intervention plays an increasingly active role in the artificial evolution of species, at a speed that differs from natural evolution.[40] The fear and opposition expressed by religious communities originate from their belief that man-induced modifications should not be made to what is believed to be the creations of 'god'.[41] Furthermore, there are rising concerns on the unforeseen economic effects from the introduction and increased flow of transgenically modified species.[42] These include the disruption of the food supply and demand trends by rising consumer preference of transgenically modified foods and contamination of non-transgenically modified agricultural outputs due to transgenic influence.[43]

References

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  2. ^ "8.7: Transgenic organisms". Biology LibreTexts. 2016-06-04. Retrieved 2020-04-08.
  3. ^ Structural biology of membrane proteins. Grisshammer, R. K. (Reinhard K.), Buchanan, Susan K. Cambridge, UK: Royal Society of Chemistry. 2006. ISBN 978-1-84755-256-3. OCLC 232638070.{{cite book}}: CS1 maint: others (link)
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  8. ^ Boxshall, Geoffrey Allan. Defaye, Danielle. Pathogens of wild and farmed fish : sea lice. ISBN 978-0-203-01132-4. OCLC 1082203471.{{cite book}}: CS1 maint: multiple names: authors list (link)
  9. ^ Pinkert, Carl A. Transgenic animal technology : a laboratory handbook. ISBN 978-0-12-410490-7. OCLC 918013885.
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  16. ^ Animal models for the study of human disease. Conn, P. Michael, (First edition ed.). Amsterdam. ISBN 978-0-12-415912-9. OCLC 847952648. {{cite book}}: |edition= has extra text (help)CS1 maint: extra punctuation (link) CS1 maint: others (link)
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  18. ^ Ramadass, P. (2011). Animal biotechnology : recent concepts and developments. Mjp Publishers. ISBN 81-8094-042-X. OCLC 942799265.
  19. ^ Platt, Jeffrey L. (2002). Xenotransplantation : basic research and clinical applications. Humana Press. ISBN 978-1-61737-127-1. OCLC 869810386.
  20. ^ "Herbicide", Wikipedia, 2020-03-17, retrieved 2020-04-08
  21. ^ "Gateway on Pesticide Hazards and Safe Pest Management". Beyond Pesticides. Retrieved 2020-04-08.
  22. ^ "Herbicide Tolerant Crops". Beyond Pesticides. Retrieved 2020-04-08.
  23. ^ "Herbicide Tolerance Technology: Glyphosate and Glufosinate | ISAAA.org". www.isaaa.org. Retrieved 2020-04-08.
  24. ^ "Golden Rice FAQs". International Rice Research Institute. 2019-01-16. Retrieved 2020-04-08.
  25. ^ "Golden rice", Wikipedia, 2020-04-01, retrieved 2020-04-08
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  27. ^ Muhammad Adil Salim (2014-02-20). "Production of biopharmaceuticals in plants". {{cite journal}}: Cite journal requires |journal= (help)
  28. ^ Hefferon, Kathleen L. (2014-10-29). Plant-derived Pharmaceuticals: Principles and Applications for Developing Countries. CABI. ISBN 978-1-78064-343-4.
  29. ^ "Other GMO Uses". GMO Answers. Retrieved 2020-04-08.
  30. ^ Innes, N. L. (July 2006). "Global Status of Commercialized Biotech/GM Crops: 2005. ISAAA Briefs No. 34. By C. James. Ithaca, NY, USA: ISAAA (2005), pp. 46, US$50.00. ISBN 1-892456-38-9". Experimental Agriculture. 42 (3): 372–372. doi:10.1017/s0014479706343797. ISSN 0014-4797.
  31. ^ "Scientists breed goats that produce spider silk". phys.org. Retrieved 2020-04-08.
  32. ^ Kochhar, H.P.S.; Gifford, G.A.; Kahn, S., "Regulatory and Biosafety Issues in Relation to Transgenic Animals in Food and Agriculture, Feeds Containing Genetically Modified Organisms (GMO) and Veterinary Biologics", Applications of Gene-Based Technologies for Improving Animal Production and Health in Developing Countries, Springer-Verlag, pp. 479–498, ISBN 1-4020-3311-7, retrieved 2020-04-08
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  34. ^ Johnson, Constance (March 2014). "Restrictions on Genetically Modified Organisms: International Protocols | Law Library of Congress". www.loc.gov. Retrieved 2020-04-08.{{cite web}}: CS1 maint: url-status (link)
  35. ^ Acosta, Luis (September 2015). "Restrictions on Genetically Modified Organisms: United States | Law Library of Congress". www.loc.gov. Retrieved 2020-04-08.{{cite web}}: CS1 maint: url-status (link)
  36. ^ Papademetriou, Theresa (March 2014). "Restrictions on Genetically Modified Organisms: European Union | Law Library of Congress". www.loc.gov. Retrieved 2020-04-08.{{cite web}}: CS1 maint: url-status (link)
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  39. ^ "x9602e07". www.fao.org. Retrieved 2020-04-08.
  40. ^ Blancke, Stefaan. "Why People Oppose GMOs Even Though Science Says They Are Safe". Scientific American. Retrieved 2020-04-27.
  41. ^ Acceptable genes? : religious traditions and genetically modified foods. Brunk, Conrad G. (Conrad Grebel), 1945-, Coward, Harold G. Albany: SUNY Press. 2009. ISBN 978-1-4384-2895-6. OCLC 314113086.{{cite book}}: CS1 maint: others (link)
  42. ^ "Dangerously playing God? - Contemporary philosophy". TLS. Retrieved 2020-04-27.
  43. ^ "Genetically modified food controversies", Wikipedia, 2020-03-30, retrieved 2020-04-08


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