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Genetically Modified Foods: Safe or Unsafe?  Caren Villano

With an ever-growing population and the problems of world hunger, there has been a high demand for an increased food supply and a better food supply. Technology has been called upon to meet this challenge. The advent of genetically engineered foods, sometimes called transgenic crops or genetically modified foods, is not a new concept, but the controversy over it is. Can these "frankenfoods" be harmful to humans? What are their effects on the environment? The following paper will focus on such questions as well as providing a better understanding of what genetically modified foods are and how they should be regulated.

Although traditional plant breeding has been around for ages, the development of recombinant DNA techniques have offered a wide range of valuable genes and methods of inserting them into the plant genomes. Two major advances in molecular biology have resulted in new plant breeding technology:

"The construction of genetic maps saturated with DNA markers, and the subsequent design of relatively simple PCR-based assays to facilitate the selection of desired alleles at closely linked loci and the resulting development of plant lines with desired combinations of traits;

The cloning and DNA sequencing of specific genes, the reassembly of specific DNA fragments into functional chimeric genes, and the transfer of such genes to single plant cells from which complete plants can be regenerated via cell and tissue culture."

(Conner et. al, 1999)

It is the second method of breeding that has come into the most light recently and offers the opportunity to develop a wide variety of new crop cultivars. Transgenic plants are usually made up of a genetic marker (antibiotic or herbicide resistance) and a well-characterized gene which expression some economically important or valuable trait. The coding region of the gene is usually fused to a promoter, most commonly used is the 35S promoter from cauliflower mosaic virus (CMV), in order to promote higher expression levels. (Snow et. al, 1997) The popular method for genetic engineering of crop plants is natural gene transfer via an Agrobacterium tumefaciens vector, a bacterium normally found in soils. The transfer-DNA (T-DNA) vector is made by inserting the desired gene fragment in between specific 25bp repeat domains in the bacterium. The vector is then inserted into the Agrobacterium and "the virulence gene products of Agrobacterium actively recognize, excise, transport, and integrate the T-DNA region into the host plant genomes." (Conner et. al, 1999) The amount of DNA transferred is only about 10kb and the nature of the gene is usually well understood. The expression of the gene introduced can also be controlled by adding additional sequences that might allow the gene to be constitutively expressed, expressed only in certain cell types, or expressed as a result of different environmental changes. This method of gene transfer, however, will only work for the natural host range of the bacterium and therefore other methods are used for additional crop plants. Such methods are uptake of naked DNA by electroporation or particle gun bombardment. The use of genetic markers, as mentioned previously, allows for the preferential growth of cultures that contain the new genetic material.

There are some variables when it comes to transfer of genetic material. The DNA may be partially inserted (truncated), inserted completely, or backwards. In addition, it can be inserted as a single copy, multiple copies, or at one or more integration sites. Some vector sequences outside of the gene of interest may become integrate as well. However, it is most common that one gene fragment is inserted at a single locus. Molecular tools such as Southern blotting and fluorescence in situ hybridization can be used to characterize the genetic material inserted after a genetically engineered plant is made.

There are four main advantages of genetically engineering plants over traditional methods. First, the source of the DNA is not limited to related wild plants. It may come from other plant species, animal, microorganisms, or even lab synthesized genes. Next, transfer of new genes is more direct and does not require many generations of breeding to recover the new cultivar. Also, while traditional methods of gene transfer may result in the transfer of closely linked or unwanted genes, genetic methods allow for a more discrete transfer of a single valuable gene. Lastly, new gene constructs can be made, using molecular biology techniques, which could not be found in wild plants used for traditional breeding.

Producing plants that are tolerant to specific herbicides is one of the largest uses of plant genetic engineering. Herbicide tolerant crops "will allow nonpersistent herbicides (e.g. glyphosphate) to be more widely used and will permit postemergence spraying of herbicide-resistant crops." (Snow et. al, 1997) Herbicides work by effecting a single enzyme, which causes a metabolic change in the plant. There are three methods by which a plant can convey herbicide resistance (OCDE, 1999):

1. Producing an enzyme which detoxified the enzyme
2. Producing an altered target enzyme which is not affected by the herbicide
3. Producing physical or physiological barriers to the uptake of the herbicide

Plants have been genetically engineered to be tolerant of a wide variety of herbicides. For the simplicity of this paper, glyphosphate-tolerant plants will be used as an example. Glyphosphate is a synthetic herbicide and is the active ingredient in Monsanto’s herbicide Roundup®. Glyphosphate works by inhibiting the enzyme 5-enolpyruvyl-3-phosphoshikimic acid synthase (EPSPS), resulting in a disruption of the plants’ biosynthesis and ultimately death. A two-fold method has been used to produce crops that are glyphosphate-resistant. One part of the method uses recombinant DNA techniques to introduce plants that encode a glyphosphate-resistant EPSPS enzyme and the other introduces an enzyme that inactivates glyphosphate, glyphosphate oxidoreductase (GOX). (OCDE, 1999) Since crops are highly sensitive to glyphosphate, it was normally used as a pre-crop emergence herbicide. These new resistant cultivars will allow application both before and after crops emerge, with little to no crop damage.

Plants that have been field-tested include beets, corn, cotton, lettuce, poplar, potato, rapeseed, soybean, tobacco, tomato, and wheat.

There is a variety of other herbicide tolerant plants that exist or are currently being developed for similar use or for use as selectable markers to identify transformed plants. Other types of herbicide tolerance that has reached field-testing stages in the U.S. are listed in Table 1.

Table 1. Herbicides and herbicide-tolerant cultivars (adapted from Snow et. al, 1997)

Devastation to crops by pests has been dealt with historically by the use of chemical pesticides. However, many of these chemicals have proven to be either ineffective or toxic. Therefore, a new strategy was needed and the miracle of recombinant technology answered the call. Plants have been produced that contain natural plant toxins that kill pests. The most common type of genetically engineered plant, the Bt plant, will be used here as an example for explanation purposes. Bt plants are created by inserting into a host plant’s genome the gene for Bacillus thuringiensis, a soil bacterium known to be a natural endotoxin. Bt toxins work by damaging the membrane or the pest’s midgut, then causing massive water uptake and eventually death. Bt toxin, however, is not harmful to humans or other invertebrates. It has been used naturally as an external pesticide, but breaks down quickly, especially in water. Transgenic Bt plants provide constant doses of the toxin and can kill pests in a single feeding. (Snow, et. al, 1997) Monsanto Corporation has recently developed a Bt corn plant to combat infestations by corn rootworms. A more widely known Bt corn exists that aids in resistance to corn borers. (Ferber, 2000) Monsanto also produces a Bt tomato and potato, while Ciba-Geigy, Mycogen Corporation, Northrup King, and Genetique SARL have their own Bt corn products. (Steinbrecher, 1996) Other insect-resistant plants have been made to produce lectins, which disrupt midgut epithelial cells, and inhibitors of certain digestive enzymes. However, none are as effective as transgenic Bt crops.

Crops are susceptible to a variety of viral, bacterial, and fungal diseases. For example, a major invader of corn is Aspergillus flavus, which can be a threat to farm animals that eat contaminated feed. A. flavus gives off a carcinogenic by-product called aflatoxin, known the cause hepatitis, cirrhosis, and death in many countries. (Brown, 1999) For this reason as well as many others, recombinant technology has developed genetically engineered plants with disease resistance. By inserting genes that code for viral coat proteins into a host cultivar, plants have been shown to have immunity to certain viral pathogens. Consequently, a variety of constructs are needed to provide resistance against a broad spectrum of viral diseases since one type of coat protein will only provide resistance to one virus or very close relatives. Fungal diseases, such as rust, mildew, and wilts, have been difficult to combat in the past. Transgenic plants carrying genes for chitinases or glucanases have been produced, which can break down chitins and carbohydrates found in fungal cell walls. This method has been introduced into tobacco, corn, potato, lettuce, squash, melon, and petunias. (Snow et. al, 1997)

There are a handful of other genetically engineered cultivars out that have helped with environmental stress tolerance or improved product quality. Some genes have been found to increase cold tolerance or drought tolerance in plants that suffer physiological stress from these factors. In addition, plants have been produced that provide better tasting or better looking product, products with increase shelf lives, altered nutritional value, or easier harvesting methods. Some transgenic plants may even be used to produce pharmaceuticals and marketable compounds.

With all this new technology comes question and fear. What are the risks of "tampering with Mother Nature"? What effects will this have on the environment? Are there health concerns consumers should be aware of? Is recombinant technology really beneficial? The following section will address some major concerns about the risks involved with genetically modified foods and recombinant technology, touching up environmental risks as well as health risks.

Many similar problems arise with pest-resistant and herbicide-resistant plants. The evolution of resistant pests and weeds termed superbugs and superweeds is one. Resistance can evolve whenever selective pressure is strong enough. If these cultivars are planted on a commercial scale, there will be strong selective pressure in that habitat, which could cause the evolution of resistant insects in a few years and nullify the effects of the transgenes. Likewise, if spraying of herbicides becomes more regular due to new cultivars, surrounding weeds could develop a resistance to the herbicide tolerant by the crop. This would cause an increase in herbicide dose or change in herbicide, as well as an increase in the amount and types of herbicides on crop plants. Ironically, chemical companies that sell weed killers are a driving force behind this research. (Steinbrecher, 1996)

Another issue is the uncertainty in whether the pest-resistant characteristic of these crops can escape to their weedy relatives causing resistant and increased weeds. (Traynor and Westwood, eds., 1999) It is also possible that if insect-resistant plants cause increased death in one particular pest, it may decrease competition and invite minor pests to become a major problem. In addition, it could cause the pest population to shift to another plant population that was once unthreatened. These effects can branch out much further. A study of Bt crops showed that "beneficial insects, so named because they prey on crop pests, were also exposed to harmful quantities of Bt." It was stated that it is possible for the effects to reach further up the foodweb to effect plants and animals consumed by humans. (Halweil, 1999).

Also, from a toxicological standpoint, further investigation is required to determine if residues from herbicide or pest resistant plants could harm key groups of organisms found in surrounding soil, such as bacteria, fungi, nematodes, and other microorganisms. (Snow et. al, 1997)

The potential risks accompanied by disease resistant plants deal mostly with viral resistance. It is possible that viral resistance can lead to the formation of new viruses, and therefore new diseases. It has been reported that naturally occurring viruses can recombine with viral fragments that are introduced to create transgenic plants, forming new viruses. Additionally, there can be many variations of this newly formed virus. (Steinbrecher, 1996)

Health risks associated with genetically modified foods are concerned with toxins, allergens, or genetic hazards. The mechanisms of food hazards fall into three main categories (Conner et. al, 1999):

Inserted genes and their expression products

Secondary and pleiotropic effects of gene expression

Insertional mutagenesis resulting from gene integration

With regards to the first category, it is not the transferred gene itself that would pose a health risk. It should be the expression of the gene and the affects of the gene product that are considered. New proteins can be synthesized that can produce unpredictable allergenic effects. For example, bean plants that were genetically modified to increase cysteine and methionine content were discarded after the discovery that the expressed protein of the transgene was highly allergenic. (Butler et. al, 1999) Consideration should be taken for foods engineered with genes from foods that commonly cause allergies, such as milk, eggs, nuts, wheat, legumes, fish, mollusks, and crustacea. ( Maryanski, 1997) However, since the products of the transgene are usually previously identified, the amount and effects of the product can be assessed before public consumption. Also, any potential risk, immunological, allergenic, toxic, or genetically hazardous, could be recognized and evaluated if health concerns arise.

More concern comes with secondary and pleiotropic effects. For example, many transgenes encode an enzyme that alters biochemical pathways. This could cause an increase or decrease in certain biochemicals. Presence of a new enzyme could cause depletion in the enzymatic substrate and subsequent build up of the enzymatic product, also. In addition, newly expressed enzymes may cause metabolites to diverge from one secondary metabolic pathway to another. (Conner et. al, 1999) These changes in metabolism can lead to an increase in toxin concentrations. Assessing toxins is a more difficult task due to limitations of animal models. Animals have high variation between experimental groups and it is challenging to attain relevant doses of transgenic foods in animals that would provide results comparable to humans. (Butler et. al, 1999) Consequently, biochemical and regulatory pathways in plants are poorly understood.

Insertional mutagenesis can disrupt or change the expression of existing genes in a host plant. Random insertion can cause inactivation of endogenous genes, producing mutant plants. Moreover, fusion proteins can be made from plant DNA and inserted DNA. Many of these genes create nonsense products or are eliminated in crop selection due to incorrect appearance. However, of most concern is the activation or upregulation of silent or low expressed genes. This is due to the fact that it is possible to activate "genes that encode enzymes in biochemical pathways toward the production of toxic secondary compounds." (Conner et. al, 1999) This becomes a greater issue when the new protein or toxic compound is expressed in the edible portion of the plant, so that the food is no longer substantially equal to its traditional counterpart.

There is a great deal of unknowns when it comes to the risks of genetically modified foods. One critic declared "foreign proteins that have never been in the human food chain will soon be consumed in large amounts. It took us 60 years to realize that DDT might have oestrogenic activities and affect humans, but we are now being asked to believe that everything is OK with [genetically modified] foods because we haven’t seen any dead bodies yet." (Butlet et. al, 1999) As result of the growing public concerns over genetically modified foods, national governments have been working to regulate production and trade of GM foods.

Currently in the United States, government agencies and the food industry share the assessment of genetically modified foods. The Food and Drug Administration (FDA), under the Federal Food, Drug, and Cosmetic Act (the Act), controls standards for safety of most foods that are derived by recombinant techniques. The FDA states that "a food or food ingredient developed by genetic engineering must meet the same rigorous safety standards under the Act as other food products, and the FDA has broad authority to take legal action against a substance that poses a hazard to the public." (FDA/CFSAN) The FDA, in 1992, published a policy that describes their guidelines for food safety and regulation of all foods developed through genetic engineering, which can be accessed on the web. Their website (http://vm.cfsan.fda.gov) provides detailed and updated information on policies regarding genetically modified crops and offers consumers information regarding what genetic engineering of crops entails. In addition, the EPA is involved in setting standards for pesticides used in and on crops, with the help of the FDA who monitors the foods. The USDA also helps regulate transgenic crops by assessing such things as the presence of food allergens. Other prestigious organizations that aid in safety assessment are the National Research Council, the World Health Organization, the Food and Agriculture Organization of the United Nations, and the Organization for Economic Cooperation and Development.

Currently, genetically modified foods do not need to be labeled as such. The FDA states that it is "not aware of information that would distinguish genetically engineered foods as a class from food developed through other methods of plant breeding, and, thus require such foods to be specially labeled to disclose the method of development." (FDA/CFSAN) Under the 1992 policy, they require GM foods to be labeled if it differs from its traditional counterpart or introduces a food allergen. The USDA has, however, developed standards for foods to be labeled "organic" and will prohibit the use of recombinant DNA crops in organic farming. (Mitten et. al, 1999)

So far, there have been no reported cases where labeling of genetically modified foods has been mandated by the FDA.

After reading extensive material on genetically modified foods, it can only be concluded that this technology is so new that a clear line cannot be drawn. It is true that genetically modified foods can provide benefits such as increased nutrients, spoilage reduction, and a decrease of chemical contamination. (Golden, 1999) On the other hand, there are many potential hazards that have not been fully investigated, as well as long- term effects that cannot be measured. A major problem is the lack of research going into this field. Many scientists are deterred from this type of research because the results tend to be negative and difficult to publish; therefore, it is difficult to receive support for this research by funding agencies.

So much is still unknown about these techniques and the possible outcomes. Genetic engineering is a powerful tool that should be used with caution and respect. If genetically modified foods are to remain in such wide use, the rest of society, along with the scientific community, should weigh the risks and benefits of them. As for now, we can only hope that in the future, the repercussion of current technology is not detrimental to humanity.

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Brown, Kathryn. New corn technology: Scientists are all eyes and ears. Environmental Health Perspectives. Vol. 107, no. 10, Oct. 1999. Pp. 514-516.

3. Butler, Decian and Tony Reichhardt. Long-term effect of GM crops serves up food for thought. Nature. Vol. 398, no. 6729, 1999. Pp. 651-653.

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FDA/CFSAN (U.S. Food and Drug Administration/Center for Food Safety and

Applied Nutrition. FDA’s policy for foods developed by biotechnology. Proceedings of American Chemical Society Symposium Series No. 605, 1995. http://vm.cfsan.fda.gov/~lrd/biopolcy.html

Ferber, Dan. New corn plant draws fire from GM food opponents. Science. Vol. 287, no. 5457, Feb. 25, 2000. p. 1390.

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Maryanski, Ph.D., James H. Bioengineered foods: Will they cause allergic reactions? U.S. Food and Drug Administration (FDA)/Center for Food Safety and Applied Nutrition (CFSAN), Oct./Nov. 1997. http://vm.cfsan.fda.gov/~dms/publargy.html

Mitten, Donna, Rob MacDonald, and Dirk Klonus. Regulation of foods derived from genetically engineered crops. Current Opinion in Biotechnology. Vol. 10, 1999. Pp. 298-302.

OCDE (Organization for Economic Cooperation and Development). Consensus document on general information concerning the genes and their enzymes that confer tolerance to glyphosphate herbicide.1999.

http://www.oecd.org/ehs/ehsmono/#BIO

Snow, Allison and Pedro Moran Palma. Commercialization of transgenic plants: potential ecological risks. BioScience. Vol. 47, Feb. 1997. Pp. 86-96.

Steinbrecher, Ricarda A. From green to gene evolution: the environmental risks of genetically engineered crops. The Ecologist. Vol. 26, Nov./Dec., 1996. Pp. 273-281.

14. Traynor, Patricia and James H. Westwood, Eds. Proceedings of a workshop on: ecological effects of pest resistance genes in managed ecosystems (Jan. 31-Feb. 3, 1999). Information Systems for Biotechnology. http://www.isb.vt.edu