1. Benefits of Genetically Modified Plants and Products
1.1. Biofortification
Micronutrient deficiencies are posing a serious threat to the health of one–half of the global population
[1]. Nutritionally enhanced food crops using modern biotechnology, conventional selective breeding, and agronomic practices to enhance nutritional values are considered an effective and alternative approach for mitigating in economically poor countries
[2]. The production of foods using biotechnology offers both benefits and threats. The production of transgenic plants is not only helpful in developing new varieties with increased nutrition but also increased resistance against biotic and abiotic factors, thereby enhancing the quality and yield of plants
[3]. In addition, plant production enables the production of materials of industrial interest, such as biodegradable plastics, vaccines (transgenic bananas that produce vaccines against hepatitis B, transgenic potatoes that are resistant to viruses, rice with increased iron and vitamin levels, with increased resistance to extreme weather, and drought,
[4][5][6].
GMO consumption maintains a healthy balance by fortifying nutritional quantity in foodstuffs that may not normally occur in them. For example, the production of “golden rice” with elevated vitamin A levels, the development of herbicide- and insecticide-resistant crops, thereby reducing crop losses, and other therapeutic substances of specific interest
[7]. Moreover, research reports have indicated that proteins produced by GMOs are non-toxic, easily digestible, and cause no allergies
[8]. Genetically modified fish grow larger, and pigs are grown with less body fat
[9]. Other studies have reported increased beneficial nutritional profiles, such as increased levels of antioxidant compounds in GMOs that may provide health benefits to humans
[10], and provide useful medicines, such as insulin for treating diabetes, from genetically engineered bacteria
[11].
1.2. Transgenic Approaches for Improving Phytochemicals and Biological Activities in Plants
Several authors have reported an improvement in the production of antioxidants, such as phenolic compounds, from transgenic plants transformed with the bacteria
Agrobacterium tumefaciens and
A. rhizogenes. Increased concentrations of phenolic compounds have also been reported to improve antimicrobial activities in
Cucumis melo [12]. Furthermore, scientists have produced transgenic lines by overexpressing genes in
Lycopersicon esculentum Mill. cv. Per with increased phenolic compound content in plants that are involved in phytoremediation
[13]. Moreover, an increase in metabolites such as triterpene and steroidal saponins, and phenolics
[14], was reported in hairy root cultures of
Trigonella foenum-graecum L., an elevated amount of phenolics acid, and flavonoids
[15] was reported in
Spagneticola calendulacea (L.) Pruski to increase food value. Increased resistance to
Botrytis cinerea in transgenic
Morus notabilis C.K. Schneid
[16].
Genetic engineering has been successful in producing transgenic rice that contains 23 times higher concentrations of carotenoids than in previous transgenic golden rice
[17]. Similarly, the genetic transformation of phytase in the transgenic soybean resulted in enhanced phytase activity by 2.5 fold compared to non-trangenic soybean
[18]. Moreover, methyltransferase genes (
VTE3 and
VTE4) from
Arabidopsis thaliana transformed into the soybean genome resulted in an enhanced α-tocopherol content by 95% more than in non-trangenic plants
[19]. The transformation of lactoferrin in dehusked rice successfully enhanced the iron contents by 120%
[20]. In another report, expression of soybean ferritin in rice resulted in an increase in the iron contents in Indica cv IRR68144 seeds, in wheat by 1.5–1.9 fold
[21], lactoferrin genes enhanced the Fe content in Maize
[22], potato, lettuce and tomato
[23], Endogenous nicotianamine content was increased by 5–10 fold in transgenic rice over-expressed with HvNaSi
[24]. Induces the proliferation of hairy roots, which increases the production of secondary metabolites. Many plant species have been transformed with
A. rhizogenes for increased production of polyphenolic antioxidants such as phenolic acids and flavonoids. Transformed plants of
Codonopsis lanceolata and
Perilla frutescens transformed with
γ-tmt genes present higher concentrations of tocopherol and phenolic compounds, thereby enhancing the antioxidant properties of such plants
[25][26]. Another approach to the recombinant production of foodstuffs is the genetic transformation of useful genes that enhance the production of beneficial compounds in plants and improve human health. Recently, researchers introduced genes into
Lycopersicon esculentum Mill. cv Ailsa Craig, to increase the accumulation of antioxidants, such as phenolic compounds
[27]. Similarly, increased amounts of phenolic compounds and resveratrol have been reported in transgenic
Rehmannia glutinosa transformed by
A. tumefaciens [28].
1.3. Transgenic Approaches for Environmental Protection
The benefits of transgenics can be assessed from an environmental point of view.
Bacillus subtilis and
Bacillus thuringiensis (Bt) strains can produce toxic proteins such as Cry or d-endotoxins
[29], that are toxic to various kinds of pests, insects, and pathogens
[30]. Bt toxins are also being used in generating trangenic crops effectively control crops pests such as CryIAc in rapeseed to control hairy bugs, diamondback moths, and cotton bollworms
[31]. Cry2Aagene in transgenic pigeon beans to control pod borers
[32], Cry3A gene in transgenic spruce to control bark beetles
[33]. According to a recent report, a significant change in the amount of herbicides and pesticide application was observed in the USA with the adoption of herbicides tolerant GM plants
[34], such as; transgenic soybean
[35], summer corn and cotton. The reduction of herbicides and pesticides can reduce the environmental impacts on cultivated land. The reduction in the application of pesticides also minimizes the use of machinery for spraying them in the field, thus reducing fossil fuel consumption in the agriculture sector.
1.4. Transgenic Approaches for Removing Allergens
Genetic transformation technology successfully incorporated genes in the plants responsible for encoding non-allergic proteins, and hypoallergenic crops, thus improving food protein equality
[36]. A significant reduction in peanut allergies was reported by silencing the gene encoding Arah2 using RNAi technology
[37]. Similar technology was used by Le et al.
[38], to silence the allergens Lyce 1.01 and Lyce 102 in tomato profiling. Similarly, allergic proteins such as Mal d from apple
[39], and GlymBd 30K from soybean
[40] were silenced using RNAi technology. In other studies, the hypoallergenic approach was effective to reduce allergenic protein in Rye gram pollen
[41]. All these studies indicate that engineered plants can also be expected to improve food quality by reducing allergens.
1.5. Transgenic Approaches for Phytoremediation
Phytoremediation is a sustainable solution for solving environmental contaminants caused by pollutants including heavy metals sediments, and inorganic and organic pollutants. Recently, the application of transgenic plants for the removal of heavy metals or organic pollutants has gained more interest
[42]. It is possible to transfer genes responsible for the hyperaccumulation of traits into target plants having remediation potential. The introduction of such genes has been reported in several plants including
A. thaliana,
[43]. Metallothioneins (MTs) confer heavy metal tolerance and accumulation in yeast. For example, the overexpression of MT genes increased the Cd tolerance in tobacco and raper seed plants
[44]. Overexpression of
phytachelatin synthase (TaPCSi) in
Nicotiana glauca significantly increased the tolerance to heavy metals such as Cd and Pb
[45]. In another study, overexpression of AtPCS, increased the phytochelatins and high resistance to arsenic
[46]. Arsenate (As), mercury (Hg), and selenium (Se) are important pollutants, and transfer approaches have been employed to remove them from the soil
[47]. Expression of the
mer B gene in transgenic
Arabidopsis thaliana resulted in more tolerance to methylmercury
[48]. Similarly, overexpression of ATP sulfurylase and CGS resulted in an increased phytovolatilization in
Brassica sp.
[49]. Enzymes such as peroxidases, laccases, peroxygenases, nitroreductases, and phosphatases play important roles in the phytodegradation of organic pollutants
[50]. These plant enzymes shown to act on organic pollutants including atrazine, chloroacetanilide, and TNT (2,4,6trinitrotoluene)
[51]. An increased rate of degradation of TNT and chloroacetanilide has been reported previously in poplar plants
[52]. Other best example of phytoremediation includes the overexpression of ECS and GS genes in
B. juncea resulted in increased tolerance to atrazine
[53].
1.6. Transgenic Approaches for Vaccine Production
The expression of antigens using biotechnology in plants has opened up a new field for the production of plant-based vaccines. Advances in transgenic research have made use of plants to serve as a bioreactor for the production of certain vaccines for curing diseases
[54]. Several plant-based vaccine antigens have been successfully expressed in plant tissues as a result of a stable expression or transient expression of genes
[55]. Plant-based vaccines are cost-effective, easy to carry, have less chance of contamination and degradation, require no medical professionals, high-tech machines, or preservation, and are less costlier than cell culture bioreactors
[56]. By conceiving the idea of an edible vaccine, the antigens genes encoding Rabies Capsid proteins such as HBsAG, and HIVgag have been successfully expressed in transgenic tomatoes
[57]. Exciting progress in achieving a high level of protein expression was achieved in transgenic carrots by Daniell et al.
[58]. Later, Scotti and their research
[59] team obtained chloroplast-based production of pharmaceuticals, vaccines, and antibodies. Transgenic
N. benthamiana plants were successfully expressed with D antigen (PV3) to use a vaccine against polio diseases Marsian, et al.
[60].
1.7. Transgenic Approach for Increased Biofuel Capacity in Plants
Lignocellulosic biomass from non-food crops has been considered a potential source of biofuel. Lignin, a major component of plant cell walls is considered a hindrance to cellulosic biofuel production. The application of biotechnology for biofuel production is gaining more interest, especially from the lignocellulosic biomass
[61]. Recently, several studies have reported the successful cloning of genes responsible for increased biomass and sugar accumulation and higher production of biofuels in transgenic lines
[62]. Several studies have reported the expression of genes in plants that are responsible for the degradation of the plant cell wall for more efficient biofuel production
[63]. A low amount of lignin was reported by downregulating the lignin biosynthetic gene 4-hydroxycinnamoyl CoA ligase (4CL)
[64]. In another study, the amount of lignin synthesized decreased to facilitate higher biofuel production in transgenic
Miscanthus sinensis [65]. Overexpression of expansin genes which helps in loosening of cell walls
[66] and successfully generated a transgenic plant with a suppressed debranching enzyme that produces soluble phytoglycogen. Vanden Wymelenberg et al.
[63] reported the involvement of several genes in the breakdown of lignin from the
Phanerochaete chrysosporium genome. Moreover, several other studies reported an alteration of lignin biosynthesis in the plant without affecting the vascular structure of plants
[24]. They reported downregulating 4-hydroxy cinnamoyl CoA ligase (4cl) responsible for the reduction of the lignin composition and an increase in the biomass of plants. Ralph et al.
[67] reported a drastic decrease in the lignin content and structure by decreasing the expression of 4-coumarate 3-hydroxylase (C3H) in alfalfa. A similar result was also observed by Chabannes et al.
[68] in transgenic tobacco by deducting the expression of cinnamoyl CoA reductase (ccR). Furthermore, the suitability of biofuel production in transgenic lines of tobacco has been investigated by downregulating O-methyl-transferase (OMT) enzyme by Blaschke et al.
[69]. They observed an increase in biomass and reduction in the lignin contents in the transgenic lines of tobacco. Other emphasizes the improvement of the fatty acid composition of plants to enhance biofuel production. Moreover, as compared to the WT plants, the transgenic line showed an increase in biofuel production in soybean by expressing diacylglycerol acyltransferase 2A (DGAT2A) from
Umbelopsis sps fungus
[70]. Furthermore, an increased caprylic acid and capric acid was observed in transgenic rapeseed by over-expressing a laurate-specific LPAAT gene from coconut
[71]. Another approach for increasing biofuel is to increase the biomass production of plants by genetic transformation approach. Manipulation of ADP glucose pyrophosphorylase resulted in an increased starch content and biofuel yield
[72]. They observed an increase in photosynthesis and biomass by overexpressing two enzymes from Cyanobacteria in the tobacco plant. Jing et al.
[73] reported an increase in the plant height and biomass by expressing the glutamine synthase gene (GSi).
1.8. Increased Stress Resistance Capacity in Plants
The excessive use of herbicides and pesticides is causing serious hazards on croplands, which makes cultivating land unsuitable for farming in the future. Recently, the introduction of GMOs has not required the use of these products. Some genetically modified crops are highly tolerant to one herbicide, instead of the multiple types of herbicides used in the field to prevent environmental damage. For example, genetically modified Roundup Ready corn is not only a glyphosate-tolerant GM corn but also is as safe and nutritious as conventional corn grain
[74]. Bt rice KND1 expressing Cry1Ab protein show high levels of resistance to insects and possess no toxic effects on human health
[75]. Similarly, insect-resistant crops include wheat, potatoes, rice, and sugarcane
[76]. Researchers have increased the level of lignin content, monolignol levels, and syringyl (S)/guaiacyl (G) in transgenic
Ipomoea batatas [L.] Lam., cv. Xushu 29 to enhance stress tolerance
[77]. The introduction of Bt corn effectively controls the application of chemical pesticides, thereby controlling the environmental pollution caused by pesticides and reducing the cost of growing crops in the field
[78]. Plants that can tolerate high salinity and long periods of drought have been reported
[79], which can help people to grow crops in cold and less irrigated areas.
2. Disadvantages of Genetically Modified Plants and Products
The introduction of genetically modified food in the market has raised some serious questions regarding human health, environmental economics, and legal issues. For instance, it has been reported that the transfer of genes poses serious genetic hazards and is associated with possible food toxicity
[10]. Once GMOs are produced and released into the environment, they can be difficult to control
[80] and any harmful products produced by these organisms will remain metabolically active as long as they survive and multiply
[80].
2.1. Human Health Hazards
Despite the advantages of GMOs, there is increasing concern about food safety and health risks. The transgene may cause undesirable developmental and physiological effects on mammals, including humans. There is a likelihood that the transformed gene may produce toxic protein or allergens or causes allergenic reaction in the human body. Moreover, other potential concerns are incomplete digestion of GMO foodstuffs in the gastrointestinal tract, which could result in the horizontal transfer of genes to the microflora and somatic cells of the intestine
[81]. Others have emphasized that the transfer of genes could cause infertility in animals, and result in allergic reactions
[82].
2.2. Environmental Risks
The release of such products and their possible impacts on the environment regenerate high monitoring of environmental biosecurity to reduce or complete eradication of risk induced by them. Apart from direct effects on human health, GM plants have environmental effects on non-target organisms such as fish, worms, bees, and insects, biodiversity loss, and gene instability
[83]. In other studies, Bt toxin produced by transgenic cotton killed many species of insect larvae, causing an imbalance in the ecosystem and food chain
[84]. It has been argued that GM crops have a serious impact on farmers and their indigenous products because they compete with GMO products
[85]. However, several previous studies reported the no-targeted impacts of novel genes transformed into the plant genome. For example, Bt maize showed potential hazards and toxic to monarch butterfly larvae that feed on milkweed leaves contaminated with pollens from Bt strains and caused delayed development, and increased maturity reported in
Ostrinia nubilalis and
Spodoptera littorals ingested with corn leaves expressing Bt CryIAS toxins
[86].
2.3. Gene Flow
The most serious problem associated with gene flow is the loss of biodiversity and often cited as potential risk. Chances of accidental cross pollination between GM crops with its wild relatives are very high, making them super-weeds that resist diverse herbicides and become difficult to control. There are several examples where gene flow from crops to the relatives weeds such as in
Beta vulgaris [87], in
Avena strigose [88], in
Brassica napus [89].
2.4. Increased Antibiotic Resistance
GM products enter the human body through food, vaccines, bacteria, or viruses. There is concern that the GM plants with bacterial resistance genes in their genome and might act as the source of drug resistance genes to the bacteria of clinical importance. Moreover, the possibility of developing antibiotic-resistant bacteria has been reported because of the frequent use of antibiotics in the genetic transformation process
[90]. Most GM products contain marker genes and genes for certain useful traits. These marker genes can build resistance to particular antibiotics, and constant consumption of these foods could result in antibiotic resistance in the human body
[91].
2.5. GMO Products Can Trigger Immune Reactions and Allergies
The introduction of new genes into plants can cause allergies by producing unexpected products (proteins and metabolites) in the plants
[92]. For instance, the immune systems of rats respond more slowly to genetically modified potatoes than to normal plants
[93]. In other studies, Bt bacteria can effectively control insects that attack crops. However, there is an equal chance of consuming Bt toxins and reacting to the mammals causing allergies
[94]. Insects, birds, and other animals that feed on certain crops may not consume genetically modified crops due to allergic reactions or poisonous products. As a result, a great number of fauna can face starvation, affecting entire food chains and causing serious threats to ecosystems
[95].
3. Biosafety Regulatory of GMO Foods and Products
Considering the importance of GMOs, several countries have managed to develop biosafety regulatory systems for the safety of GM foods and products. The regulations surrounding GMOs are complex and the rate of consumer acceptance is crucial, which results in reduced usage of GMOs. GMOs and their products have been facing severe controversies and hurdles from the public sector, NGOs, and environmental organizations
[96]. Different governments have different approaches to tackling the products of GMOs, which vary widely, and are country-specific
[97]. Within the European Union (EU), Directive 2001/18/EL contains the biosafety regulation for the use of GMOs. It defines and control environmental release (case by case) evaluation of the environmental risk of GMOs
[98]. Other directives such as 98/81/CE for the number of GM microorganisms, directive 1946/2003 for transboundary movement of GMOs, 1829/2003 for GM food and feed have been authorized
[98]. GMO products have already been supplied to the EU market with appropriate labelling and identification methods under the title NOVWL-FOOD classification in May 1997
[99]. Currently, European Union-based legislation accepted the products of natural gene transfer methods, such as conjugation, auto-cloning, and gene transduction, and are considered non-genetically modified organisms
[100]. However, EU has banned the application of clustered regularly interspaced short palindromic repeats genome (CRISPR-Cas9) editing technology, but the US has allowed the use of Cas9, which enables geneticists and medical researchers to edit parts of the genome
[101]. Similarly, The Canadian Food Inspection Agency (CFIA) is responsible for regulating GM plants, a field trial of GM crops, their approval and commercial release in Canada. It also plays a major role in assessing impacts on biodiversity and environment, possible gene flow and impacts on non-targeted organisms
[102]. In India, safety guidelines for GMOs such as research, field trails of GM foods and products assessment environmental risk assessment have been adopted from Rules 1989
[102]. Ministry of Environment Forest, Forest and Climate Change (MoEFCC) in association with the department of Biotechnology (DBT) recently adopted new guidelines for the environmental risk assessment of GE plants in India
[103]. So far, Bt cotton (insect-resistant transgenic cotton) is the only GM plant to have been approved for commercial cultivation in India. Over 20 different GM plants with insect resistance, abiotic resistance, herbicidal resistance, enhance nutritional traits etc. have been under field trials
[104].
The adoption of biosafety regulations is strongly impacted by the economical and political situation of countries. Despite their differences in approach and adoption of GMOs regulations framework, countries such as Brazil, Argentina, Chile, Mexico, Honduras, Costa Rica, and Uruguay were the first Latina America to approve GM crops
[105][106]. Other Latin American nations such as Peru, Venezuela, and Ecuador implemented a complete ban on the application/test and import of GMOs
[107][108]. To harmonize the regulations concerning GM products, Latin American countries such as Brazil, Argentina, Paraguay, Uruguay and Chile singed a declaration which legalizes the application of gene-edited products (case by case) amid strict regulation
[109]. Countries such as Brazil and Argentina are major exporters of GM crops (cotton, soybean and Maize) and recently adopted legal provisions to allow the cultivation of GM crops
[109], which not only play a bigger role in their economy but also play a key role to rapid adaption of biosafety law and regulations
[109][110][111][112]. The Secretariat of Agriculture, livestock, fisheries and Food (SAGyO) is responsible for the regulation of GMOs, for conducting field tests, release and commercial application in Argentina
[113]. While, national technological Biosafety committee (CTNBio), is responsible for scientific research on GMOs, field tests, risk assessment and assessing the safety of GMOs in Brazil
[113]. Legal provisions of biosafety regulations are under discussion in the countries such as El Salvador, Mexico, Peru, Costa Rica, The Dominican Republic, and Ecuador. Other Latin American countries including Barbados, Dominica, Guyana, Haiti, The Bahamas, and Belize has no legal provision to deal with GMOs so far
[114].
African nations can benefit from the adoption of the biosafety regulation to mitigate the food crisis, nutrition and economic livelihood
[115][116][117]. The rapid adoption of GM crops regulations can address the existing food crises and ease hunger that exists in African countries. Some African countries welcomed GM technology and rapidly proceed for adopting GM crops to enhance agricultural production efficiency and increase the nutritional values of plants
[118][119]. While, other African countries oppose GM technology stating its safety concerns, environmental and human health issues, intellectual property rights and ethical uncertainties
[120][121][122]. However, several anti-GMO debates and controversies related to the safety of GMOs, and their impacts on human health and environmental issues are major hindrances in adopting biosafety regulations among African nations
[123][124]. Despite hindrances, the majority of African nations (47 countries) currently allow the cultivation of GMO crops
[125]. South Africa is the first African nation to enact the regulatory framework to allow the cultivation, export and import of GM crops
[125], and other African countries are interested in collaborating and harmonising the regulation concerning GM crops (African Biosafety network of expertise ABNE, 2019
[126]. Successful confined field trials have been conducted for maize, sorghum, cassava and Bt cotton with a wide range of traits in Kanya
[126][127]. It has been reported that early acceptance of biosafety regulation has been hindered by inadequate GM technology knowledge in Kenya, and less awareness and knowledge of GM technology in the countries like Ghana and Nigeria,
[128]. Moreover, a slow and delayed GM adoption rate in Tanzania have been reported
[129]. The restrictive regulations, lack of information and awareness of the GM crops regulations have played an important role to obstruct the commercialization of GM crops in African nations
[130][131]. In addition, opposition to biosafety bills, laws and regulations from NGOs, media, political parties social and economic factors and multinational companies have further helped to restrict the adoption of GM crops regulations in these countries
[132][133][134][135].
Similarly, China adopts strict safety evaluation of GM plants and products and promulgated a whole set of biosafety laws, regulations and management systems considering its national situation and international norms and regulations. For the implementation of biosafety regulation, the Ministry of Agriculture (MOA) played a pioneering role in the implementation of regulations, and administrative Measures for the Safety Assessment of Agricultural GMOs
[136], and developed the guidelines for safety inspection of field trials, research, processing, import and exports of GM crops
[137]. Recently, MOA has promulgated a set of new regulations to shorten the process involved commercialization of GM crops
[138] and introduced biosafety guidelines to regulate gene-edited crops
[139]. Similarly, Korea has released a set of laws and regulations guidelines for GMOs and GMO products. To ensure biosafety, proper assessment of GMOs is carried out according to the guidelines of the Korea Food and Drug Administration (KFDA)
[140]. It is clear from the above data that there exists a diverse range of regulations and frameworks supporting the research and commercialization of GM crops. For the efficient and successful functioning of these regulations, there is a need for a collective and synergetic approach, and closer interaction among the different government, non-government agencies, and private sectors which may play a diverse role in coordinating and harmonizing biosafety issues. Moreover, for adopting unified biosafety regulations, regional and international agencies should focus on the proper dissemination of information on biosafety regulations and public awareness about biosafety measures.