Genetically Modified Organisms (GMOs): Transgenic Crops and Recombinant DNA Technology

People have been altering the genomes of plants and animals for many years using traditional breeding techniques. Artificial selection for specific, desired traits has resulted in a variety of different organisms, ranging from sweet corn to hairless cats. But this artificial selection, in which organisms that exhibit specific traits are chosen to breed subsequent generations, has been limited to naturally occurring variations. In recent decades, however, advances in the field of genetic engineering have allowed for precise control over the genetic changes introduced into an organism. Today, we can incorporate new genes from one species into a completely unrelated species through genetic engineering, optimizing agricultural performance or facilitating the production of valuable pharmaceutical substances. Crop plants, farm animals, and soil bacteria are some of the more prominent examples of organisms that have been subject to genetic engineering.

Agricultural plants are one of the most frequently cited examples of genetically modified organisms (GMOs). Some benefits of genetic engineering in agriculture are increased crop yields, reduced costs for food or drug production, reduced need for pesticides, enhanced nutrient composition and food quality, resistance to pests and disease, greater food security, and medical benefits to the world's growing population. Advances have also been made in developing crops that mature faster and tolerate aluminum, boron, salt, drought, frost, and other environmental stressors, allowing plants to grow in conditions where they might not otherwise flourish (Table 1; Takeda & Matsuoka, 2008). Other applications include the production of nonprotein (bioplastic) or nonindustrial (ornamental plant) products. A number of animals have also been genetically engineered to increase yield and decrease susceptibility to disease. For example, salmon have been engineered to grow larger (Figure 1) and mature faster (Table 1), and cattle have been enhanced to exhibit resistance to mad cow disease (United States Department of Energy, 2007).

Table 1: Examples of GMOs Resulting from Agricultural Biotechnology

Genetically Conferred Trait	Example Organism	Genetic Change
APPROVED COMMERCIAL PRODUCTS
Herbicide tolerance	Soybean	Glyphosate herbicide (Roundup) tolerance conferred by expression of a glyphosate-tolerant form of the plant enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) isolated from the soil bacterium Agrobacterium tumefaciens, strain CP4
Insect resistance	Corn	Resistance to insect pests, specifically the European corn borer, through expression of the insecticidal protein Cry1Ab from Bacillus thuringiensis
Altered fatty acid composition	Canola	High laurate levels achieved by inserting the gene for ACP thioesterase from the California bay tree Umbellularia californica
Virus resistance	Plum	Resistance to plum pox virus conferred by insertion of a coat protein (CP) gene from the virus
PRODUCTS STILL IN DEVELOPMENT
Vitamin enrichment	Rice	Three genes for the manufacture of beta-carotene, a precursor to vitamin A, in the endosperm of the rice prevent its removal (from husks) during milling
Vaccines	Tobacco	Hepatitis B virus surface antigen (HBsAg) produced in transgenic tobacco induces immune response when injected into mice
Oral vaccines	Maize	Fusion protein (F) from Newcastle disease virus (NDV) expressed in corn seeds induces an immune response when fed to chickens
Faster maturation	Coho salmon	A type 1 growth hormone gene injected into fertilized fish eggs results in 6.2% retention of the vector at one year of age, as well as significantly increased growth rates

The pharmaceutical industry is another frontier for the use of GMOs. In 1986, human growth hormone was the first protein pharmaceutical made in plants (Barta et al., 1986), and in 1989, the first antibody was produced (Hiatt et al., 1989). Both research groups used tobacco, which has since dominated the industry as the most intensively studied and utilized plant species for the expression of foreign genes (Ma et al., 2003). As of 2003, several types of antibodies produced in plants had made it to clinical trials. The use of genetically modified animals has also been indispensible in medical research. Transgenic animals are routinely bred to carry human genes, or mutations in specific genes, thus allowing the study of the progression and genetic determinants of various diseases.

Many industries stand to benefit from additional GMO research. For instance, a number of microorganisms are being considered as future clean fuel producers and biodegraders. In addition, genetically modified plants may someday be used to produce recombinant vaccines. In fact, the concept of an oral vaccine expressed in plants (fruits and vegetables) for direct consumption by individuals is being examined as a possible solution to the spread of disease in underdeveloped countries, one that would greatly reduce the costs associated with conducting large-scale vaccination campaigns. Work is currently underway to develop plant-derived vaccine candidates in potatoes and lettuce for hepatitis B virus (HBV), enterotoxigenic Escherichia coli (ETEC), and Norwalk virus. Scientists are also looking into the production of other commercially valuable proteins in plants, such as spider silk protein and polymers that are used in surgery or tissue replacement (Ma et al., 2003). Genetically modified animals have even been used to grow transplant tissues and human transplant organs, a concept called xenotransplantation. The rich variety of uses for GMOs provides a number of valuable benefits to humans, but many people also worry about potential risks.

Despite the fact that the genes being transferred occur naturally in other species, there are unknown consequences to altering the natural state of an organism through foreign gene expression. After all, such alterations can change the organism's metabolism, growth rate, and/or response to external environmental factors. These consequences influence not only the GMO itself, but also the natural environment in which that organism is allowed to proliferate. Potential health risks to humans include the possibility of exposure to new allergens in genetically modified foods, as well as the transfer of antibiotic-resistant genes to gut flora.

Horizontal gene transfer of pesticide, herbicide, or antibiotic resistance to other organisms would not only put humans at risk, but it would also cause ecological imbalances, allowing previously innocuous plants to grow uncontrolled, thus promoting the spread of disease among both plants and animals. Although the possibility of horizontal gene transfer between GMOs and other organisms cannot be denied, in reality, this risk is considered to be quite low. Horizontal gene transfer occurs naturally at a very low rate and, in most cases, cannot be simulated in an optimized laboratory environment without active modification of the target genome to increase susceptibility (Ma et al., 2003).

In contrast, the alarming consequences of vertical gene transfer between GMOs and their wild-type counterparts have been highlighted by studying transgenic fish released into wild populations of the same species (Muir & Howard, 1999). The enhanced mating advantages of the genetically modified fish led to a reduction in the viability of their offspring. Thus, when a new transgene is introduced into a wild fish population, it propagates and may eventually threaten the viability of both the wild-type and the genetically modified organisms.

In 1971, the first debate over the risks to humans of exposure to GMOs began when a common intestinal microorganism, E. coli, was infected with DNA from a tumor-inducing virus (Devos et al., 2007). Initially, safety issues were a concern to individuals working in laboratories with GMOs, as well as nearby residents. However, later debate arose over concerns that recombinant organisms might be used as weapons. The growing debate, initially restricted to scientists, eventually spread to the public, and in 1974, the National Institutes of Health (NIH) established the Recombinant DNA Advisory Committee to begin to address some of these issues.

In the 1980s, when deliberate releases of GMOs to the environment were beginning to occur, the U.S. had very few regulations in place. Adherence to the guidelines provided by the NIH was voluntary for industry. Also during the 1980s, the use of transgenic plants was becoming a valuable endeavor for production of new pharmaceuticals, and individual companies, institutions, and whole countries were beginning to view biotechnology as a lucrative means of making money (Devos et al., 2007). Worldwide commercialization of biotech products sparked new debate over the patentability of living organisms, the adverse effects of exposure to recombinant proteins, confidentiality issues, the morality and credibility of scientists, the role of government in regulating science, and other issues. In the U.S., the Congressional Office of Technology Assessment initiatives were developed, and they were eventually adopted worldwide as a top-down approach to advising policymakers by forecasting the societal impacts of GMOs.

Then, in 1986, a publication by the Organization for Economic Cooperation and Development (OECD), called "Recombinant DNA Safety Considerations," became the first intergovernmental document to address issues surrounding the use of GMOs. This document recommended that risk assessments be performed on a case-by-case basis. Since then, the case-by-case approach to risk assessment for genetically modified products has been widely accepted; however, the U.S. has generally taken a product-based approach to assessment, whereas the European approach is more process based (Devos et al., 2007). Although in the past, thorough regulation was lacking in many countries, governments worldwide are now meeting the demands of the public and implementing stricter testing and labeling requirements for genetically modified crops.

Proponents of the use of GMOs believe that, with adequate research, these organisms can be safely commercialized. There are many experimental variations for expression and control of engineered genes that can be applied to minimize potential risks. Some of these practices are already necessary as a result of new legislation, such as avoiding superfluous DNA transfer (vector sequences) and replacing selectable marker genes commonly used in the lab (antibiotic resistance) with innocuous plant-derived markers (Ma et al., 2003). Issues such as the risk of vaccine-expressing plants being mixed in with normal foodstuffs might be overcome by having built-in identification factors, such as pigmentation, that facilitate monitoring and separation of genetically modified products from non-GMOs. Other built-in control techniques include having inducible promoters (e.g., induced by stress, chemicals, etc.), geographic isolation, using male-sterile plants, and separate growing seasons.

GMOs benefit mankind when used for purposes such as increasing the availability and quality of food and medical care, and contributing to a cleaner environment. If used wisely, they could result in an improved economy without doing more harm than good, and they could also make the most of their potential to alleviate hunger and disease worldwide. However, the full potential of GMOs cannot be realized without due diligence and thorough attention to the risks associated with each new GMO on a case-by-case basis.