Genetically Modified Foods: A Boon or Bane for Human Health 

Abstract  

Genetic modification is a special set of gene that alters the genetic machinery of such living organisms as animals, plants, or microorganisms. Combining genes from different organisms is known as recombinant DNA technology and the resulting organism is said to be genetically modified organisms (GMOs), genetically engineered or transgenic. GMOs have widespread applications as they are used in biological and medical research, production of pharmaceutical drugs and agriculture. It has enhanced food production by making plant less vulnerable to drought, frost, insects and viruses and by enabling plants to uptake soil nutrients effectively. It has also improved the quality and nutritive value of food crops like golden rice and flavour-saver tomato. As revealed by some studies, GM foods also have harmful effects on the human body. Antibiotic resistance marker genes (ARMGs), like kanamycin, are commonly used for creation of GM foods and for distinguishing it with non-GM foods. Theoretical studies put forward that consumption of these foods may cause the development of human diseases which are immune to antibiotics. Animal studies with certain GM foods like potatoes have shown toxicity on several organs besides responsible for accelerated aging and insulin regulation. It may also alter the hematological, biochemical and immunological parameters. Another risk associated with consumption of GM food is of allergenicity. Many childrens in US and Europe have developed life-threatening allergies to GM foods like peanuts. It increases levels of insulin like growth factor (IGF-1), which is known to promote cancers like that of breast, prostrate and colorectal by inhibiting apoptosis. As many argumental theories favouring and opposing GM foods are available during our literature search, we conclude that further studies on a large sample of human population are required in order to approve the beneficial impact versus the risk posed by GM foods on human health.  

Keywords: GM food, Nutritive value, Toxicity, Allergy, Human Health, Apoptosis 

1. Introduction 

One of the most important indispensable things for human life is food. Apart from taking a nutritious and healthy food, everyone has to be aware whether the food is safe for consumption or not. Alternation is being done in plant genome to increase the production rate of food by the use of different conventional & modern techniques. Genetic engineering and genome editing of plants are the widely used methods, in addition to plant breeding, to improve or enhance quality of foods besides increasing their production in order to meet the demand of fast-growing population of the world (Paparini & Romano-Spica, 2004). Genetically Modified (GM) food means any food which is derived from with the help of genetically engineered organism. Genetically manipulated biotech-crops, available in the global market, have one of the basic characters: insects or disease resistance, herbicides tolerance and enhanced nutritional value (Seralini et al., 2011). In1994, Flavr-Savr tomato, developed in 1980s, was the first approved GM food for human consumption in US. GM food comprises about 90% of corn, cotton and soya bean plants in US by 2014-15. Golden Rice, developed in 1990s, was approved by FDA in 2018 and it was first commercialized in 2021. Recently, first GM edible crop that has been approved in India in 2022 is Dhara Mustard Hybrid-11 (DMH-11), after BT cotton in 2002. The main aim of this review article is to assess GM foods in terms of their benefit vs risk on human health. 

2. Search strategy

We searched published/in press research and review articles or reports from Scopus, Google Scholar, MEDLINE/ PubMed and WHO Library. Some chapter of books are also searched from WorldCat. For our write-up, we then compared the discussion and conclusion sections of the recent articles published within the 5-10 years. 

3. Genetically Modified Foods

In 1946, scientists, Lederberg and Tatum, first discovered that DNA can be naturally transferred between the bacteria. There are several methods like conjugation for transferring of DNA. The artificial combination of two genes from different organisms is known as genetic engineering or recombinant DNA (r-DNA) technology. Resulting organism is termed as Transgenic or Genetically Modified Organisms (GMOs) which may be animals, plants or microorganisms. Their genetic material is altered in the lab to create new varieties of plants, animals and organisms with desired characteristics. GMOs can be referred as GM foods when humans are the direct consumers and as GM feeds when it is meant for animals only. 

All GM products   are   completely   identical   to  their   natural samples  and also in  their  basic characteristics,  such  as colour, smell  and  appearance. All over the  world,  many different  products  have  been  regenerated  by  genetic modification  and  have  received  a  patent  for  use  as  feed  for  humans  and  animals. Various types of agricultural products are derived from GM  species  such as rice, tomatoes, corn, soybeans, wheat, potatoes and the most  popular  products  are  of soy,  cotton,  corn  and  rapeseed (Turhan & Kafkas, 2013). In addition to these products, sunflower, rice, pumpkin, cassava, papaya and peanuts are also grown as GM foods. Some research is still ongoing on the crops like banana, strawberry, raspberry, cherry, pepper, pineapple and melon. Among grain crops, only the herbicide resistance gene  is  transmitted  to  rice. The two crops, wheat and barley, have high economic value but there is no transgenic product derived from them (Cicekci, 2008). Genetic modification studies are also conducted on animals.  Besides plant and animal products, GMO technology is also  used  for  microorganisms.  Genetically modified microorganisms such as bacteria, fungi and molds are used for obtaining enzymes and amino acids and also for food additives used in various industries such as bread, cheese, grape and beer products (Uzogara, 2000).  In dairy and other food industries, lactic acid bacteria are usually used as a starter culture for the production of fermented foods such as cheese, yogurt, kefir and sausage. These cultures give a specific smell to a food and besides ensuring the maturation of fermented food (Sybesma et al., 2006; Ahmed, 2002). 

4. Status of approved and cultivated GM Crops in different countries 

Studies have been done on a variety of genetically modified (GM) crops for the past four decades. In 1983, an antibiotic-resistant tobacco plant was used to produce the first GM plant. In early 1990s, virus resistant tobacco was introduced as transgenic crop first commercialized by China. In 1994, Food and Drug Administration (FDA) had approved the first transgenic food ‘Flavr Savr tomato’ for marketing in the USA. This modification was done to delay the ripening process in tomato, after harvesting. Marketing approval was given in 1995 to some transgenic crops viz. Bacillus thuringiensis (Bt) corn/maize (Ciba-Geigy), Bt cotton (Monsanto), Bt potatoes (Monsanto), glyphosate (herbicide) resistant soybeans (Monsanto),canola with modified oil composition (Calgene) and extra delayed ripening tomatoes (DNAP, Zeneca/Peto, and Monsanto) (James, 2011). As per ISAAA report of 2017, although developing countries continued to rise in terms of plantation area of the crops compared to industrialized countries since 2012 but USA leads in plantation and production of GM crops among list of developed and industrialized countries (Briefs, 2017). Of the 24 countries planted biotech/GM crops in 2017, 19 are developing and 5 are industrialized countries. The top five includes USA, Brazil, Argentina, Canada and India. The four major planted GM crops are cotton, soyabean, maize and canola. One or the other GM crops that are available in these countries include soybean, corn, tomatoes, cotton, potatoes, lettuce, canola, eggplant, strawberries, carrots, etc. Sugar beet, apples and papaya are also commercially used as GM crops (Giraldo et al., 2019). The use of gene technology in food production has become interesting due to increased requirement of food as well as its improved quality. With the application of gene technology to plants and animals, goals can be achieved more quickly than by traditional selection.  

5. Methods of Production of GM Crops 

A foreign gene that has been integrated into the genome of animals, plants or microorganisms is called a transgene and the recipient organism is known as transgenic. Transgenes are those genes they have known traits or mutated variants of known genes. In most of the cases marker genes are also used because of their identification of transgenic organism. The two broad methods utilized for production of GM crops are i) Gene Addition and ii) Gene Silencing and of these, first method is more commonly used (Figure 1). The integration of transgene into the cell is carried out by the listed methods: (a) Transduction using bacteriophages (b) Transfer using modified viruses and plasmids (c) Transgene injection using pronuclear microinjection (Wong et al., 2000) (d) Electroporation method, a higher permeability of cell membrane is achieved. Gene silencing technique utilizes small interfering RNA (siRNA) and micro RNA (miRNA). 

Developed countries, having material and intellectual capacities, leads the studies on transgenic technology for production increase and improved food quality. However, developing countries that need this technology to exceed the food shortage cannot afford it (Smolin & Grosvenor, 2000). Hence, gene technology is not a remedy to prevent the world from starvation. Transgenic seeds that developed countries can provide to developing countries to diminish the rate of malnutrition seems to be the best idea of genetic engineering.  

6. Methods of Detection of GMOs in food 

Various forms of PCR and ELISA-based methods are the common and usual methods while biosensors and microarray-based methods are the latest ones employed for detection of GMOs in food (Deisingh and Badri 2005; Guertler et al., 2009). These methods utilize either genetic elements or proteins or even specific markers of GMOs for the identification. 20pg of genomic DNA in GM brinjal has been detected by multiplex and real time PCR methods (Ballari et al., 2012).Another recent study has revealed a new rapid method of molecular characterization of GM plants (Giraldo et al., 2021). 

7. Benefits of GM Foods 

GM foods have both advantages and disadvantages. Recent studies have provided an update on current status of GM crops under cultivation and also focused on issues challenging the widespread adoption of the crops (Kumar et al., 2020; Rodríguez e al., 2022). A comparative analysis of benefit and risks of these foods is shown in Table 2 and Figure 2.

7.1. Improved Nutritional values 

The importance of nutrition and food in human health has got enormous attention in recent years (Kenward et al., 1999). Malnutrition is common in third world countries where impoverished people depend on a single crop such as rice as their diet. However, rice does not contain appropriate amounts of all necessary nutrients to prevent malnutrition. One example of nutrient-deficient disease is night blindness, caused due to deficiency of vitamin A. Biofortification is one of the useful modern methods utilized in GM plants for enhancement of nutritional contents in the crops compared to the method of addition of nutrients during food processing. Researchers of Swiss Federal Institute of Technology Institute created a strain of "golden" rice, which contain a high content of beta-carotene (vitamin A) (Sakakibara & Saito, 2006; Napier, 2019). The first Golden Rice was engineered by inserting the PSY gene from plant Narcissus pseudonarcissus and phytoene desaturase (CrtI) gene from the bacteria Erwinia uredovora, which can catalyze phytoene to retinol precursors. However, according to both the FAO and WHO, the carotenoid content of Golden Rice did not meet the minimum nutritional requirements, not even if consumed as staple food. Nevertheless, the biotechnology company Syngenta developed Golden Rice2 in 2005 by utilizing PSY gene from maize. This new crop increased carotenoid content by up to 23-fold compared to the original Golden Rice and to a significant level to reduce vitamin A deficiency in childrens (Sakakibara & Saito, 2006; Ye et al., 2000). Studies are going on for its adaptation to local cultivation (Sakakibara & Saito, 2006).Apart from producing biofortified crops to combat malnutrition, biotechnology enables the cultivation of healthier foods having antioxidant and anti-cancerous properties which is beneficial for the general public (Campestrini et al, 2019). Studies involving example of GM crops biofortified for various effects on human and climate are shown in Table 1.  

7.2. Disease resistant 

Plant diseases are caused by many bacteria, fungi and viruses. Plant biologists are working to create plants with genetically-engineered resistance to protect them from diseases (Alexander et al., 2017). For example, viruses from the Geminiviridae family infect a wide range of plants worldwide, which include tomato, maize, bean, cotton, potato, and pepper, among others. These viruses bring about considerable agricultural damage, which results in lower yields. Mosaic, leaf curling, mottle, vein yellowing, leaf yellowing, crumpling, and rugosity are just some of the signs of the diseases that Gemini viruses cause (Loriato et al., 2020; Es et al., 2019). For instance, recent studies have shown the efficacy of the CRISPR-Cas system in developing disease resistant in many plants like Nicotiana benthamiana, rice, banana, tomato, etc affected either by virus, bacteria or fungus (Ji et al., 2015; Zaidi et al., 2020).  

7.3. Drought/Salinity and Heat/Cold tolerant 

 As the world population grows day- by-day and more land is utilized for housing instead of agriculture for production of food, farmers will need more lands for growing the crops for fulfil the requirement of upcoming generation. A current study has reviewed on the recent progress in using genetic engineering to improve or increase individual abiotic stress tolerance in plants, most commonly in rice, wheat, cotton, tomato, tomato, soyabean, potato and maize besides focussing on enhance tolerance to multiple stresses using gene pyramiding approach in most of the above mentioned plants (Esmaeili et al 2022). Plants are created that can be resist for long periods of drought or high salt content in soil and ground water, which will help the farmers to grow crops in formerly inhospitable places (Zhang & Blumwald, 2001;Tang, 2000). For example, maize is grown mostly by applying dry farming practices, even though it does not well manage in drought (Tykot, Burger & Van der Merwe, 2006). Recent research has shown that genome editing at a negative regulator of ethylene response, the ARGOS8 locus, generates drought-tolerant crops (Shi et al., 2016).  

Recent studies were done on enhanced salt tolerance in rice (Kim et al. 2020) and that of improved tolerance in soyabean (Nguyen et al. 2019; Wei et al. 2019). New studies have also focused on enhanced drought tolerance in cotton, soyabean, rice and wheat (Basso et al. 2021; Molinari et al. 2020; Huang et al. 2019; Gonzalez et al. 2019). Other studies were done on improving heat stress tolerance in transgenic crops like cotton, tobacco and tomato (Batcho et al. 2021; Singh et al. 2021; Meng et al. 2015). An antifreeze gene is taken from cold water fish and has been introduced into plants such as potato and tobacco. With this antifreeze gene, these plants are able to tolerate cold temperatures that normally would kill unmodified seedlings (Kenwardet al., 1999).  

7.4. Herbicides Tolerant 

 Genetically-engineered crop plants resistant to powerful herbicides could help in preventing environmental damage by minimizing the use of herbicides. For example, a strain of genetically modified soybeans created by Monsanto was not affected by Roundup, a glyphosate-based herbicide. These soybeans which when grown, require only one application of the herbicide, leading to reduction in production cost and limiting the dangers of run-off of agricultural wastes (Ohkawaet al., 1999).  

7.5. Eliminating the use of pesticides 

 A large amount of chemical pesticides are used annually. Use of pesticides cause potential health hazards, and can poison the water supply and cause harm to the environment (Anderson et al, 2019; FAO, Plant Production and Protection Division, 2020). Application of chemical pesticides can be gradually stopped by growing GM crops like BT corn (Moellenbecket al., 2001).  

7.6. Pharmaceuticals/medication 

 Vaccines and medicines are generally very expensive and take long-time to produce and sometimes they require a special storage condition, especially during transportation. Recently, researchers are working to develop edible vaccines in potatoes and tomatoes (Daniell et al., 2001; Perr, 2001). These vaccines will be cost-effective, easier to transport, store, and administer than traditional injectable vaccines.  

8. Risk of GM Food/Products on Health of Animals and Humans  

GMOs are widely used and consumed around the developed countries and now started gaining approval or acceptance in developing countries, but there arises a question of the health risks caused by their use in food. Some GM products can cause allergies, toxicity or low immunity while others can cause organ failure or diseases (Gizaw 2019). In a report published in 2005, the World Health Organization (WHO) stated that GMOs  have  potential  risks  to  human  health  and  do  not  have  a history  of  a  safe  food  product for consumption. Insertion of a new gene in the genome   of   a   modified   food   product   may   cause   undesirable developmental and  physiological  effects (Cellini et al, 2004).  Despite all its advantages, transgenic products have certain risks. Foreign genes can cause unpredictable  changes  both  by  increasing  the  nutritional  value  of  some  foods  and by reducing the value of some other foods (Uzogara, 2000). Recent studies  conducted in EU countries and China have found greater percentage of people opposed to GM foods in comparison to those favouring it (Popek and Halagarda 2017; Deng and Hu 2019). In an another  study,  it  was  noticed  that  the  attitude  of consumers  to  GMOs  is  "positive"  in  the  United  States  and  "negative"  in  other countries (Oz et al., 2018). Recent review articles have shown both positive and negative impact of GM products on human health (Bawa & Anilakumar, 2013; Zhang et al., 2016; Dzhumanova & Nazarova, 2022). A survey conducted in US reported that after avoiding GM foods there is an improvement in health of the respondents (Smith, 2017). Original research articles on experimental animals showing the risks posed by GM foods on human health are compiled in Table 3. Although studies have been done, showing minimization of some of the risks by genetic engineering of the foods (Table 4). 

8.1. Higher death rates and organ damage in experimental animals 

Mice fed with Roundup Ready soy showed changes in the pancreatic cells and significant reduction in digestive enzymes (Malatesta et al., 2003). In another case, pancreas was enlarged when animals were fed with GM potato (Tudisco et al., 2006).Animals fed with GM soy showed lesions, toxicity and altered enzymes production in kidney tests (Vecchio et al., 2004) while there was slower growth rate of brain in animals fed with GM potatoes (Tudisco et al., 2006). 

8.2. Digestive tract problem and Liver damage 

In an earlier study it was suggested that since digestive tract is the first and largest point of contact with foods besides processing of toxins by liver, so it should be the first target site of GM food risk assessment (Pusztai, 2001; Smith, 2002). Rats fed with the GNA lectin potatoes had smaller and partially deteriorated livers (Pusztai, 2002). Rats fed GM corn showed altered liver enzyme production and higher metabolic activity (Burns, 2002). GM soya caused liver lesions and toxicity in rabbits (Tudisco et al., 2006) while structural changes in liver of rats were observed when they were fed with Roundup Ready soybeans (Ermakova, 2007). GM corn/maize (MON 810) fed rats showed hepato-renal toxicity (Seralini et al., 2007). A recent study has shown severe stomach inflammation and increased weight of uteri in pigs fed with a combine diet of GM soya and GM maize (Carman et al., 2013).  

8.3. Immune reactions involving allergies  

Allergic reactions occur when the immune system reacts to something as foreign. All GM foods are created by transferring foreign gene from different organisms to the crop plants and several reports have shown that they cause reactions. According to a study, soyabean modified with Brazil-nut gene to enhance nutritional value caused severe allergic reaction (Otsu and Dreskin, 2011) and was prohibited in 1994 (Ozdogan & Ekmen, 2002). GM potatoes caused low immunity in animals (Tudisco et al., 2006). Like the GM soy protein, BT protein, CRY1Ab, conferring insect resistance in GM corn/maize (MON 810) has some of its amino acid sequence identical to an allergen found in egg yolk. Another study has shown an inflammatory response of GM peas in mice and it might cause deadly allergic reactions in people (Dutton et al., 2006). Scientists found a new unique protein in GM soybeans, in addition to the herbicide tolerant protein, was able to bind with IgE antibodies and provoke dangerous allergic reactions (Hoff et al., 2007). BT-toxin produced in GM crops is of different potential from that of bacterial (BT-toxins) spray used for insect control in organic and traditional farming and forestry. The plant produced toxin is more toxic than natural varieties (Romeis et al., 2004).  

Sometimes genetically modified products which can cause health problems can be mixed into natural products during production period. StarLink is the trading name of a genetically modified corn developed by Aventis Crop Science Company. This corn includes Cry9C protein and it is defined as “a potential alergenic” by US Environmental Protection Agency (EPA) so in 1998 EPA stated that StarLink can only be used as animal feed or in industry but it cannot be used as human food (Batista et al., 2005; Vergragt & Brown, 2008). In their study, Gupta et al. have reported that in cotton farm and factory workers who pick and load cotton producing BT toxin, some upper respiratory tract, eye and skin related allergies was observed (Gupta et al., 2005).  Concerns about the Cry9C protein, a type of insect pest-resistance protein, have been voiced, given its greater heat stability and a possible longer digesting time. Yet, no direct association exists between allergic reactions and consuming GM food (Giraldo et al, 2020; Zhang, et al, 2016). 

8.4. Risk of Cancer  

GMOs can have carcinogenic effects, directly or indirectly. Herbicide resistant chemicals, bromoxynil and glufosinate, used for cotton, soya and corn are known to cause cancer (Haspolat, 2012). Hormone and hormone-like substances affect human health in a negative way. Genetically modified bovine growth hormone (rBGH), used to enhance milk production in cattle, causes an increase of insulin-like growth factor (IGF-I) in milk. The increase of IGF-I levels in blood leads to lymphoma, breast, ovarian and uterine, prostate, colon, lung and pancreatic cancer (http://www.forum.gidagundemi.com, 2011). Consuming the animal products contaminated by high level of dioxin was accounted for long term toxic and carcinogenic effects on human (Aydin, 2000). 

8.5. Alteration in Reproductivity  

Reproductive failures are reported in animals fed with GM foods (Smith 2002). Mice and rats fed with GM soybeans showed dramatic changes in their testicles. The organs were dark blue instead of pink in rats while young sperm cells were altered in mice (Oliveri et al, 2006). Embryos of mice fed with GM soy showed temporary changes in their DNA function, compared to that of mice fed with non-GM soy (Prescott et al., 2005). 

8.6.  Antibiotic Resistance 

During genetic modification, antibiotics are used as selection markers to differentiate successfully transformed bacteria form untransformed one. Some studies have shown the risk of transfer of genes of antibiotic resistance into bacteria within the group of good and bad microbes of digestive tract of animals and humans, consuming GM foods (Ray et al., 2012; Gilbert 2013). 

9.  Conclusion and Future Perspectives 

Our literature search of various databases showed a mixed response to the acceptability of GM foods due to its beneficial and harmful effects as described above. More studies on animals and on large sample of humans are required to approve the higher benefits and minimal risk of GM foods on human health. 

Ethical statement 

The present manuscript is a review article. Therefore, studies on humans and animals are not involved. 

Declaration of Competing Interest 

None. 

Data availability 

It is a review article, so it summarizes the results of other authors. 

Acknowledgements 

Authors acknowledge the academic support from the University Authorities. 

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Table 1.  GM crops involving biofortification and their applications (Adapted from Rodriguez et al., 2022) 

Table 2. Comparative analysis of benefit and risks of commonly cultivated GM foods 

Table 3. Research articles reporting risk involved in public health by intake of GM Foods (Adapted from Gizaw, 2019) 

Table 4:  Minimization of risk in GM crops through Genetic Engineering (Adapted from Rodríguez et al., 2022) 

Captions: 

Figure 1: Methods of Production of GM Foods 

Figure 2: Repercussions of the GM Technology  

               (Adapted from Basu et al. 2010)