Genetic engineering risks

SIGNIFICANCE: The application of biotechnology, specifically genetic engineering, creates real and foreseeable risks to humans and to the environment. Furthermore, like any new technology, it may cause unforeseen problems. How to predict the occurrence and severity of both anticipated and unexpected problems resulting from biotechnology is a subject of much debate in the scientific community.

The Nature of Biotechnological Risks

Most of the potential risks of biotechnology center on the use of transgenic organisms. Potential hazards can result from the specific protein products of newly inserted or modified genes; interactions between existing, altered, and new protein products; the movement of transgenes into unintended organisms; or changes in the behavior, ecology, or fitness of transgenic organisms. It is not the process of removing, recombining, or inserting DNA that usually causes problems. Genetically modifying an organism using laboratory techniques creates a plant, animal, or microbe that has DNA and RNA that is fundamentally the same as that found in nature.

Risks to Human Health and Safety

The problem most likely to result from ingesting genetically modified (GM) foods is unexpected allergenicity. Certain foods, such as milk or Brazil nuts, contain allergenic proteins that, if placed into other foods using recombinant DNA technology, could cause the same allergic reactions as the food from which the allergenic protein originally came. Scientists and policymakers will, no doubt, guard against or severely restrict the movement of known allergens into the food supply. New or unknown allergens, however, could necessitate extensive testing of each GM food product prior to general public consumption. Safety testing will be especially important for proteins that have no known history of human consumption.

Unknown, nonfunctional genes that produce compounds harmful or toxic to humans and animals could become functional as a result of the random insertion of transgenes into an organism. Unlike traditional breeding methods, recombinant DNA technology provides scientists with the ability to introduce specific genes without extra genetic material. These methods, however, usually cannot control where the gene is inserted within the target genome. As a result, transgenes are randomly placed among all the genes that an organism possesses, and sometimes insertional mutagenesis occurs. This is the disruption of a previously functional gene by the newly inserted gene. This same process may also activate previously inactive genes residing in the target genome. Early testing of transgenic organisms would easily reveal those with acute toxicity problems; however, testing for problems caused by the long-term intake of new proteins is difficult.

Many human and animal disease organisms are becoming resistant to antibiotics. Some scientists worry that biotechnology may accelerate that process. Recombinant DNA technologies usually require the use of antibiotic resistance genes as “reporter” genes in order to identify cells that have been genetically modified. Consequently, most transgenic plants contain antibiotic resistance genes that are actively expressed. Although unlikely, it is possible that resistance genes could be transferred from plants to bacteria or that the existence of plants carrying active antibiotic resistance genes could encourage the selection of antibiotic-resistant bacteria. As long as scientists continue using naturally occurring antibiotic resistance genes that are already commonly found in native bacterial populations, there is little reason to believe that plants with these genes will affect the rate of bacteria becoming resistant to antibiotics.

Another possible problem associated with antibiotic resistance genes is the reduction or loss of antibiotic activity in individuals who are taking antibiotic medication while eating foods containing antibiotic resistance proteins. Would the antibiotic be rendered useless if transgenic foods were consumed? Scientists have found that this is not the case for the most commonly used resistance gene, NPTII (neomycin phosphotransferase II), which inactivates and provides resistance to kanamycin and neomycin. Studies have shown this protein to be completely safe to humans, to be broken down in the human gut, and to be present in the current food supply. Each person consumes, on average, more than one million kanamycin-resistant bacteria daily through the ingestion of fresh fruit and vegetables. These results are probably similar for other naturally occurring resistance genes of bacterial origin.

Risks to the Environment

If environmentally advantageous genes are added to transgenic crops, then those crops, or crop-weed hybrids, may become weeds, or their weediness may increase. For example, tolerance to high-salt environments is a useful and highly desirable trait for many food crops. The addition of transgenes for salt tolerance may allow crop-weed hybrids to displace naturally occurring salt-tolerant species in high-salt environments. Most crop plants are poor competitors in natural ecosystems and probably would not become weeds even with the addition of one or a few genes conferring some competitive advantage. Hybrids between crops and related weed species, however, can show increased weediness, and certain transgenes may also contribute to increased weediness.

Biotechnology may accelerate the development of difficult-to-control pests. Crops and domesticated animals are usually protected from important diseases and insect pests by specific host resistance genes. Genetic resistance is the most efficient, effective, and environmentally friendly means for controlling and preventing agricultural losses caused by pests. Such genes are bred into plants and animals by mating desirable genotypes to those that carry genes for resistance. This method is limited to those species that can interbreed. Biotechnology provides breeders with methods for moving resistance genes across species barriers, which was not possible prior to the 1980s. Bacteria and viruses, however, have been moving bits of DNA in a horizontal fashion (that is, across species and kingdom barriers) since the beginning of life. The widespread use of an effective, specific host resistance gene in domesticated species historically has led to adaptation in the pest population, eventually making the resistance gene ineffective. Recombinant methods will likely accelerate the loss of resistance genes as compared with traditional methods because one resistance gene can be expressed simultaneously in many species, is often continuously expressed at high levels within the host, and will more likely be used over large areas because of the immediate economic benefits such a gene will bring to a grower or producer.

Hybrid plants carrying genes that increase fitness—through, for example, disease resistance or drought tolerance—may decrease the native genetic diversity of a wild population through competitive or selection advantage. As new genes or genes from unrelated species are developed and put into domesticated species, engineered genes may move, by sexual outcrossing, into related wild populations. Gene flow from nontransgenic species into wild species has been taking place ever since crops were first domesticated, and there is little evidence that such gene flow has decreased genetic diversity. In most situations, transgene flow will likewise have little or no detrimental effect on the genetic diversity of wild populations; however, frequent migration of transgenes for greatly increased fitness could have a significant impact on rare native genes in the world’s centers of diversity. A center of diversity harbors most of the natural genetic resources for a given crop and is a region in which wild relatives of a crop exist in nature. These centers are vital resources for plant breeders seeking to improve crop plants. The impact of new transgenes on such centers should be fully investigated before transgenic crops are grown near their own center of diversity.

In 2013, Kevin Esvelt, then a fellow at Harvard University's Wyss Institute for Biologically Inspired Engineering devised a way to use a precise gene editing technology known as CRISPR (clustered regularly interspaced short palindromic repeats) to build a gene drive. A gene drive is a genetic alteration that ensures that specific, altered genes are inherited by all progeny in every successive generation. In normal inheritance, altered genes are only inherited by 50 percent of progeny. While gene drives are touted by proponents as a way to quickly eradicate dangerous pests, such as mosquitoes that spread malaria to humans, the technology has the potential to render entire species extinct in the wild, which could have unforeseen long-term environmental consequences.

Researchers are developing ways to safeguard CRISPR-based gene drive experiments to prevent accidentally spreading gene drives to wild populations. In 2019, researchers at Cornell University demonstrated that using synthetic target sites and split drives in gene-drive experiments are two viable ways, other than physical containment, to limit the unintended release of organisms carrying gene drives outside of the lab. Additional progress in the effort to safeguard CRISPR-based gene drive experiments came in 2023 when researchers at the University of California (UC) San Diego successfully developed a flexible genetic hacking system that allows spilt drives to be safely converted into full drives.

Impact and Applications

The risks associated with genetically modified organisms have been both overstated and understated. Proponents of biotechnology have downplayed likely problems, while opponents have exaggerated the risks of the unknown. As with any new technology, there will be unforeseen problems; however, as long as transgenic organisms are scientifically and objectively evaluated on a case-by-case basis prior to release or use, society should be able to avoid the obvious and most likely problems associated with biotechnology and benefit from its application.

Key terms

• fitnessthe probability of a particular genotype surviving to maturity and reproducing
• genomethe genetic content of a single set of chromosomes
• genotypethe genetic makeup of an individual, referring to some or all of its specific genetic traits
• selectiona natural or artificial process that removes genotypes of lower fitness from the population and results in the inheritance of traits from surviving individuals
• transgenic organisman organism that has had its genome deliberately modified using genetic engineering techniques and that is usually capable of transmitting those changes to offspring

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