Perspective Chapter: GMO Foods and Our Health

Abstract

GMO foods come from genetically modified plants that were genetically edited to create healthier and more environmentally tolerant plants that increase nutritional value, resist pesticides, and repel insects. The increase in herbicide uses and the alteration of plant DNA expression has opened the door for harmful toxins expressed in the plant’s genetic make-up. These transgenes produce protein-based toxins, such as in corn, which mimic other plant-based toxins that are harmful to humans when consumed. The domino effect of herbicide resistance is that the use of glyphosate (Roundup) increased for commercial purposes because of the resistance to the herbicide. Toxic levels of glyphosate have been found to lead to health problems, including having been identified as a carcinogen-causing agent. The effects of a two-fold alteration of foods genetically and chemically could very well be the Trojan horse of the twenty-first century. Elevated levels of toxins in the food chain may be the link to the declining health status worldwide with higher rates of cancer, diabetes, obesity, Alzheimer’s disease, and neurologic conditions. So, how did GMO foods end up being a detriment instead of a benefit?

1. Introduction

The growing world population is at a cross-roads. One estimation of the earth’s population states that it will be around 9 billion people by the year 2050. This increase in population has created a demand for a 70% increase in food production by that time to be able to feed such a large population [1]. Through technological advancements in the GMO field, genetic engineering (GE), and improving crops resistant to infection, viruses, herbicides, and environmental stressors, rates of the most common genetically modified organism (GMO) foods produced have steadily increased by 1.2% annually, but is not at the estimated 2.4% annual increase needed to meet the food demands by 2050 [1, 2].

To better understand what genetically modified organisms are, we need to review the types of GE techniques briefly. Transgene GE is when genes are inserted into a DNA or RNA strand from another species usually from bacterial or mold microorganisms [1]. These specific DNA/RNA sequences control the behavior of the organism/plant through dominant traits. The second category is the transgene-free GMO process that emerged in the early 2000’s. This process uses artificial and natural genetic traits to insert gene sequences into an RNA and/or DNA strand for a desired trait. Genomic engineering in the form of cluster regulatory interspaced short palindromic repeats (CRISPR) technology uses insertion and deletion techniques that are more efficient, and cost-effective, but unfortunately are not regulated as stringently due to its ease in the knock in and knock out process of genetic sequences at specific locations. The principle of CRISPR technology has been founded on the action of RNA fragments known as a guide RNA (gRNA) along with a bacterial component that is a CRISPR-associated endonuclease (Cas9) made up of around 20 sequences that makes up the CAS-9 binding “scaffold.” This CRISPR/Cas9 creates the platform for the enzyme (cutter) to replace, modify, or delete traits from the DNA fragment and alter its genetic make-up, function, and development [3].

Over the last 20 years, technological advances in Genetically modified organisms have not only improved, but now dominate most processes of how crops, seeds, and plant products impact food production. There will be roughly 11 billion people on the plants by the end of the century, thus projections for the future provide a snapshot of the food production needs/deficit facing the world and the importance of GE foods to achieve food security by then [2]. The premise that the increased crop production will help feed more people in the world and combat food shortages is part of the justification for integrating GMO crops along with increased profits and less impact on the environment. The background for needing more food production stems from estimations of undernourished people to be around 690 million as recent as 2019 [4].

This forward thinking has been the evolution of centuries of farmers cross breeding plants that are better suited to their environment, insect resistant, and mold resistant to improve crop production and variety, farming viability, and crop quality [5]. The only difference today is that this takes place in a laboratory through genetic engineering, thus the changes are no longer naturally occurring, but rather science has incorporated DNA sequence editing to improve plant crops [5]. This chapter will review the impact that such changes to plants and our food has had on the environment and subsequently how these changes are editing the narrative of our health, increases in specific disease processes, increases in autism, exposure to harmful herbicides, increased inflammatory processes, changes in the composition of plants that increase food allergy exposures, and pollination cross-contamination of non-GMO crops [4, 6].

The general population is skeptical of GMO foods since they only have a basic knowledge of what it is and whether it is safe to consume [2, 7]. This dialog controls the narrative and hence has sparked labeling strategies to provide clear symbols or statements of whether the product is a GMO food. This visual cue helps people make informed decisions about what foods they choose to eat. The public acceptance of GMO foods is higher in North America compared to those in the EU [2].

To ensure a product is not GMO based, it should read 100% organic, GMO-Free, or non-GMO project verified. This type of labeling communicates clearly for the consumer to increase transparency and purchasing confidence [7]. One other attempt to control the biosafety of GMO plants resulted in an international agreement called the Cartagena Protocol which was finalized in 2003. This agreement was created to protect the biodiversity of natural plants from the risk of exposure to GMO crops; thereby requiring countries to agree to the entry of specific GMO products/organisms into their country [2].

2. Development of GMO foods

In 1973, the discovery of extraction of DNA from one plant species and the introduction of that DNA into another plant species was the advent of GMO genetic engineering for the first time via laboratory experimentation efforts [8]. This first step in genetic engineering led to the first ever antibiotic resistant crops of tobacco and petunia plants in 1983. This evolution of the science led to a variety of virus resistant tobacco crops in 1990 [8]. The United States approved the first GMO food for human consumption in 1994 which was a tomato variety called the Flavr Savr to increase its shelf life and slow the ripening process. The development of GMO crops such as corn, soy, rice, cotton, and wheat include genetic engineering of specific DNA traits to include greater yields of crops, healthier crops that resist certain molds and bacteria, and herbicide resistant crops to allow for increased herbicide use in the prevention of weed growth in the fields [5, 6]. The highest producer of GMO crops is the United States of America (USA) (see Figure 1) with Brazil being the second largest GMO producer. Since GMO engineering began making technological advancements in genetic engineering, the production of these crops have increased 112 fold since 1996 [8]. The time that it takes to bring a GMO product to fruition is around 13 years. This timeline includes studying the impact and/or risks of altering a genetic traits in plants. The average cost for these studies and the development of such products is estimated to be around $140 million USD before it makes it to the market [7]. The rigor that is involved is not conveyed to the general public; however, the unforeseen risks are also not communicated, such as the increased herbicide use on these GMO plants and how that may or may not impact one’s health [6, 9].

Figure 1.

Percentage of farmland for GMO corn and soy in the USA [1].

With great strides in improving crops for productivity and heartier plant strains, genetic engineering took a left turn to make the crops resistant to the herbicide Roundup from Monsanto. This resistance to herbicides created a domino effect that has not stopped since [8]. The ability to use more herbicide on plants to eliminate weeds improved crop production, but also contributed to the development of commercial roundup (Glyphosate) products with additional ingredients that when used together, increase the penetration of the herbicide into the plant that results in detrimental effects on cellular health in humans. Glyphosate has been classified as “probably carcinogenic to humans” by the International Agency for Research on Cancer (IARC) [6].

3. The detriment of glyphosate in and on GMO foods

To better understand the impact of glyphosate based herbicides (GBH), the amount of this product used annually is around 750,000 tons and is anticipated to increase to as much as 920,000 tons by 2025 [6]. People may ask, if the plant resists the herbicide, then how can it be detrimental? The issue lies in the unforeseen impact on the plant. The advent of this product improved field preparation since there is less tillage needed; however, when you look at the increased use of this product on the crop field, the half-life of the GBH in the soil ranges from 23 to 958 days. This reflects the turnover of crops as much as a three-year period with spraying occurring with each application of crops planted per season. Now, think of the toxic affect and accumulation of this herbicide in the soil that has not reached its half-life and thus provides the foundation for plants to grow and absorb more and more chemically tainted water into the plant itself, not to mention the contamination of aquatic ecosystems from runoff during rain events [10]. This chemical accumulation translates into absorption of toxic levels of GBH within the plant. This has created an unforeseen concern for foods that have elevated levels of GBH along with potential protein-based toxins from genetic modifications of the plant. This combination of exposures has created the perfect storm for chemically induced cellular changes and health issues to humans, animals, and fish due to long-term exposure to these toxins, especially if consumed in high levels (see Table 1) [6, 10].

Table 1.

How glyphosate impacts humans, non-mammals/rodents, and fish on a cellular level.

The long-term exposure of glyphosate and its metabolites in foods have been found in vegetables, fruit, cereal/cereal products, rice, beans, and honey [10]. These levels are traced by many European countries for safe levels of the herbicide in foods consumed by the public [10]. The question to ask is: when you eat multiple products daily with “acceptable levels” of glyphosate, what does that translate to with relation to toxicity for daily exposure with extended half-life periods calculated into the equation? Is this why higher levels of multiple disease processes and cancers are increasing?

Exposure to commercial glyphosate products have been found to cause oxidative stress and increases the inflammatory response through the proinflammatory cytokine interleukin-6 (IL-6) genes and tumor necrosis factor alpha gene upregulation in humans [6, 11]. Inflammation is a hallmark to many chronic diseases, the aging process, and cancer [14]. GBH is the trojan horse of this century and no one is the wiser for the impact this chemical has had on the decline of human health and the increase in chronic diseases, the damage caused to the central nervous system, and the decrease in glucose metabolism. Glyphosate is metabolized via the colon and has been found to cause a higher incidence of celiac disease when glyphosate is ingested in addition to other intestinal problems [10]. Is there a link to the increase in cancers and the levels of glyphosate in our foods? This should be explored further.

A systematic review conducted by Costas-Ferria, C.; Duran, R.; and Faro, L. concluded that GBH and other formulations pose “detrimental effects on the human nervous system” which involves Parkinson’s and Alzheimer’s. A table of their review shows studies that link exposure to GBH and/or its other formulations to an increase in autism, intellectual disabilities, cancer, alterations of glucose uptake in the brain, altered cell death pathways, and increased blood brain barrier (BBB) permeability. Glyphosate and its metabolites were found to have induced damage to the central nervous system (CNS) from lactate dehydrogenase (LDH) increases and stating that GBH and its metabolite (AMPA) “reduced the viability of human cells and increased the leakage of LDH” [6]. Most would not think much about LDH increases; but increased levels of LDH have clinical significance for being used prognostically to determine the progression of various types of cancers, is also used as a staging marker for non-seminomatous testicular cancer, and it’s levels are high with intracranial hemorrhage or organ damage [15]. GBH was found to cause a decrease in cellular metabolism and induced a “negative regulation in the expression of TUBB3 and GAP43 genes” which are integral in short term memory and memory retention [6, 15]. Could this be the link to Alzheimer’s rates increasing? Further studies are needed to support the link definitively between GBH and how it plays a role in neurological/cognitive decline.

Furthermore, the Costas-Ferria et al. noted in their systematic review that commercial glyphosate products used on rodents for research purposes showed increased anxiety/depressive behaviors as well as impairment in working memory, decreased movement/locomotion and decreased sociability patterns [6]. One such study cited in their review found that maternal rodents had a decreased licking behavior with a later increase documented. There was an impairment of neurogenesis and plasticity in the hippocampus. This decrease in remodeling could be the cause for decreased maternal bonding. Decreased neural development of offspring born early was also a finding. Exposure to GBH has been found to modify multiple microRNAs expressed in brain development and linked as a cause of multiple diseases [6].

In summary, GBH exposure over time is linked to alterations in DNA and RNA function as well as impairment of various cellular/metabolic processes, preventing cellular repair, negatively impacting neurological and cognitive functioning, and causing inflammatory triggers that result in chronic diseases and/or cancers (see Table 2) [6, 11, 12]. It is important to distinguish between GMO foods and the use of GBH products used on these foods. This distinction reveals that GBH products are negatively impacting health trends worldwide.

Table 2.

Multiple study findings of how glyphosate/GBH impacts human health negatively.

4. Plant genome editing challenges

There are multiple ways to edit plant-based genetic sequencing. The traditional way of breeding and crossbreeding plants incorporated cross-pollination of two varieties of the same type of plant that has desirable traits to combine via this route, also known as Mendel’s Law of Inheritance [9]. The down side to this type of process is the time it takes to yield a new crop variety after backcrossing over many plant generations to get the end product of a new variety which usually takes a minimum of 10 or more years to accomplish the favorable trait outcomes desired [5]. Transgene-free GMO technology is a challenge in ensuring the safety due to less regulation than transgene GE products since it uses artificial genes in addition to natural genes to alter the genetics of the plant for specific traits to emerge [1]. This brings up the risk to foreign proteins and possible immune responses to this foreign/artificial genetic strain in foods that have been classified safe to eat by the federal food and drug administration (FDA). This issue is highly controversial due to less regulatory monitoring of biotechnology [1].

The issue of antibiotic resistance is of great concern when discussing GE foods and how that translates when looking at long-term health implications to the public [1, 16]. However, now that this concern has been identified, scientists are more careful to not use potential genes that would potentially cause antibiotic resistance. This does not mean that new findings and edited genes will not cause this issue in the future, but scientists have begun to address these precautions to ensure ethical practices going forward in the field of genetic engineering. One caveat to consider in this particular conversation is the focus of antibiotic use in animals raised for human consumption and the risk that poses when super germs are created because antibiotics are no longer effective [16].

Now, the process of GE is more streamlined and has progressed from Zinc Finger DNA-binding domains, although not considered a very efficient process to the newer CRISPR/Cas9 approach that cleaves DNA through an RNA guided genome editing process. This new process is revolutionary in its efficiency for genome editing through cleavage of Cas9-directed DNA sequences that are target and non-target strands called a double-strand DNA break (DSB). This process results in DNA repair that allows for the insertion or deletion (also known as gene knock in or gene knock out) of specific DNA traits through regulation of gene expression by binding DNA or RNA specific sequences [3, 5, 9]. One such example includes the mildew-resistant locus (MLO) gene deleted (knock out) in barley, wheat, and tomato plants to help resist having a powder coated mildew infection that destroys crops. Such knockouts have improved crop viability and resistance to various fungal, bacterial, and viral infections for plants such as rice, cotton, fruits, and vegetables [9]. The ability to protect crops with a natural resistance to such infections allows for healthier plant growth and production of bio sustainable products. This translates into better quality foods, less waste, and more profit for farmers [9].

The long-term effects of this type of genome editing remains to be determined. Better quality crops, yields, infection resistant, and insect, salinity, and drought tolerant varieties have been created in an efficient manner when gene editing isolates and knocks out the weak trait expressed in the plant. The ethical dilemma of GE in plants has bled over into genome editing concerns for human genome alterations that may have long-term consequences such as questionable immune responses and/or targeted gene therapy outcomes [3]. This technology should be considered for humans only once the risk–benefit ratio has been thoroughly assessed [3].

5. GMO food health benefits

When genetic engineering occurs for the good of the public and prevention of malnutrition in areas lacking good nutrition, it can be beneficial. Currently, GMO products make up approximately 66% of the world’s diet [2]. There are varieties of rice that are embedded with Beta-carotene in a product called Golden Rice [17]. There have been tomatoes genetically edited to have 4–5 times higher GABA levels. For those with a gluten allergy, researchers have used the CRISPR/Cas9 approach to create a low-gluten wheat for those with celiac disease that have a gluten allergy and are limited in what they can eat, this opens up the door for more food options and safer food selections [8]. Another genome-edited product that the public is benefiting from is lettuce that has increased levels of beta-carotene, thiamine, and vitamin C. Overall, when the focus is improved health and avoiding herbicides, questionable genetic altering practices, and following a code of scientific ethics, the general population benefits greatly from these advances in technology.

Gene editing through the CRISPR/Cas technology has expanded its scope and focus since the advent of fungal, infection, and viral resistant strains of plants. Over the past few years, since CRISPR/Cas technology advancements have occurred, genetic scientists have begun to look to what is possible in improving the health of humans through improving vitamin, mineral, and protein supplementation/amplification with this very same knock out and knock in technique to enrich our foods for better health, decreased risk of cardiovascular and/or cancer risk [4, 9]. Developing countries are benefitting from this technology in the form of biofortified rice with beta-carotene to help reduce/eliminated childhood blindness from malnutrition [1]. One such example is when a tomato plant was genetically altered to increase the bioavailability of Lycopene through the editing of the carotenoid metabolic pathway [9]. Another example includes the increased protein production in barley when d-hordelein was subject to the knockout process, as was a low-gluten transgene-free wheat was developed for those with a high sensitivity to gluten [9]. One major concern to consider for patients with allergies is to understand that the potential for new allergies/sensitivities may occur when a new gene product comes to market such as when a transfer of a protein from one plant to another in merged. However, with CRISPR Cas-9, scientists have been able to remove 35 of the 45 gene responsible for gliadin synthesis (gluten) linked to gluten/wheat allergy and/or celiac disease with an astounding 85% reduction in immunoreactivity [1].

6. GMO risks

The ability to edit plant gene expression to resist herbicides is a risk that most people would not consider. When one thinks of resisting an herbicide, it sounds like less herbicide will be used on the plants; however, quite the contrary, more herbicide is being used to ensure less weeds in the crops. The half-life of glyphosate (Round Up) is a concern because it stays in the soil and accumulates [6, 10]. This accumulation enters the roots of the plant with water and enters the water supply through run off thereby tainting the eco system with lasting effects of Round Up exposure and/or ingestion. The side-effects are discussed at length earlier in the chapter. This trojan horse uses GMO products/plants to make huge profits at the expense of the public [6, 10]

In 1966 the transfer of the Brazil nut protein to soybeans provided a way for the protein from the Brazil nut to be inserted “knocked in” to the soybean, hence this addition of a foreign protein into the soybean triggered allergic reactions from participants that volunteered to evaluate the new product. One major concern to consider for patients with allergies is to understand that the potential for new allergies/sensitivities may occur when a new gene product comes to market such as when a transfer of a protein from one plant to another in merged [4]. When an unfamiliar protein binds to Immunoglobulin E the risk of the protein converting to an allergen in increased. The other risk is that of toxins in new genetically altered foods when a transgene encodes a specific toxin that is now overexpressed [4].

The good news about glyphosate and the health of GMO foods is that glyphosate was to be removed from public home use sales by its new owner Bayer. Glyphosate’s previous owner, Monsanto, sold the Roundup company to Bayer in 2018. Bayer stopped selling Roundup to the public in 2023 due to excessive lawsuits regarding glyphosate (Roundup) and its impact on people’s health and having caused cancer in those who used it for home use [18]. The sale of commercial glyphosate herbicide has yet to be discontinued from the market amid multi-million-dollar lawsuits. If Bayer’s mounting legal troubles are any indication, the commercial formulation may be under scrutiny as well for removal in the commercial sector in the future. One other point to ponder, Bayer is a pharmaceutical company that sells prescriptions for various disease processes, and it owns Round Up which is known to cause various chronic conditions and cancer. Do you think this is a conflict of interest for Bayer to sell the product that causes different disease processes and/or cause damage to humans’ health and then turn around and benefit from selling the “treatment/cure?”

7. Conclusion

In conclusion, foods that have undergone insertion/deletion of specific DNA or RNA strands to improve the plant’s quality and nutritional value through an ethical and thoughtful purpose poses little threat. The threats lie within the intent and lack of thorough research to determine the risk of human consumption and what that looks like. This includes the exposure to toxic levels of glyphosate, allergens, and foreign components within the altered plant that may be toxic to humans. However, if food products are only released once determined safe for human consumption and are labeled correctly for its modifications and risk for exposure to allergens, then this can be avoided with the appropriate warnings (i.e.: may contain nut protein) [7]. Through trial and error in the development of this new technology, ethical policies and procedures have been initiated to ensure public safety [1, 7]. The time and cost that researchers place on the safety of new products takes years before any GMO products are released for production/planting and processing for foods to be consumed by the public [5, 9].

The public needs to always be weary of the trojan horse from herbicides such as glyphosate (Round Up) and other chemicals that can alter the health, benefit, and purpose of the GMO plant/food [10]. Also, be aware of foods that may increase food allergies due to GE manipulation and cross-contamination of non-GMO plants with GE crops. All scenarios are possible. The takeaway for those wanting to know if it is safe is that there will always be anomalies, but for most GMO products, they are safe to consume. Look for labels that state that the GMO product/food is free from herbicides as well and read food allergy warnings on the package to ensure there is not a risk of food allergy exposure [7]. Knowledge is your best advocate. The more you know, the better equipped you will be to understand the risks and benefits of this new technology and embrace it or make an informed decision to choose/purchase non-GMO products instead [7].

Conflict of interest

The author declares no conflict of interest.