Genetic Engineering

Summary

Genetic engineering, also known as genetic modification, is an interdisciplinary scientific technique using molecular techniques to directly alter the basic genetic blueprint (DNA) of bacteria, plants, animals, humans, and other living organisms to achieve or enhance a specific trait or useful characteristic. Genetic engineering, though often controversial, is used in diverse areas, including medicine and agriculture, to diagnose and treat diseases, produce industrial products, neutralize pollutants, create hardier and higher-yielding crops, create vaccines, and perform scientific research. The genetic engineering process uses the tools of molecular genetics to explore and change living systems on a fundamental level and has revolutionized scientists' ability to understand, modify, and enhance the natural world.

Definition and Basic Principles

Genetic engineering is the direct and purposeful alteration of an organism's DNA—the basic genetic blueprints of a bacterium, plant, animal, human, or other living organism—to add or enhance a specific characteristic or trait. Although genetic engineering is most often discussed in the controversial arenas of crop production or theoretical human genetic manipulation, genetic engineering is used in diverse areas such as medicine, industry, and agriculture to treat disease, diagnose problems, produce industrial products, convert industrial waste, create hardier crops, and perform better scientific research. Genetic engineering was also employed in creating several vaccines against COVID-19.

The focus of genetic engineering is the gene. Genes are the basic units of inheritance that contain information and instructions for the creation, maintenance, and reproduction of living organisms. Genes are composed of DNA, a highly organized molecule located in almost every cell of an organism's body. In genetic engineering, scientists add very specific pieces of useful genetic material to another organism's genes to change an organism's natural characteristics.

Genetic engineering was made possible by the development of new molecular genetic procedures, often called recombinant DNA technology, that can identify the particular DNA sequence of a gene or an entire genome, allow scientists to find the genetic material that codes for useful or desired features, and then insert the new material into the correct place in another organism's genetic code.

Organisms that have had new genetic material inserted into their code are referred to as genetically modified organisms (GMOs) or genetically engineered organisms (GEOs). Examples of GMOs range from corn that has been engineered to produce an innate insecticide to cows that produce milk containing human insulin.

Background and History

Before modern genetic engineering was possible, farmers had long selected for desired traits by breeding plants and animals with the desirable traits, a process known as selective breeding. Brewers and bakers also changed grains and flour into preferred products such as beer and bread through the use of small organisms called yeast and the process of fermentation.

By the early twentieth century, plant scientists had begun to use the work done by Gregor Mendel in the nineteenth century on the inheritance patterns of specific plant features to more formally introduce improvements in a plant species in a process called classic selection. However, the features of the basic unit of inheritance were not known until James D. Watson and Francis Crick identified the structure of DNA in 1953 with the double-helix model.

The nature of DNA and the technology to manipulate and modify the genetics of an organism was not available until twenty years later, when the first successful recombinant organism was created by Herbert Boyer and Stanley Cohen. Boyer and his laboratory had isolated an enzyme that could precisely cut segments of DNA in an organism, and Cohen found a way to introduce antibiotic-carrying plasmids into bacteria and a way to isolate and clone the genes in the plasmids. They combined their knowledge to create a way to clone genetically engineered molecules in foreign cells. Their discoveries led to the creation of a quick and easy way to make chemicals such as human growth hormone and synthetic insulin.

After Boyer and Cohen, many other scientists worked with recombinant DNA techniques to improve the procedures and develop a variety of genetically modified organisms designed to meet specific scientific, agricultural, industrial, and medical needs. Over time, these techniques and applications in genetic engineering spawned the multibillion-dollar biotechnology industry.

As the biotechnology industry grew and genetically modified organisms became more widespread, it became important to define which organisms were genetically modified organisms and which were products of classic selection. It also became necessary to determine if living organisms produced through genetic engineering could be patented by the companies and universities designing them. In 1980, the US Supreme Court ruled in the case Diamond v. Chakrabarty that genetically altered life-forms can be patented.

In 1982, the US Food and Drug Administration (FDA) approved the first consumer product developed through modern genetic engineering: a biosynthetic human insulin, sold under the trademark Humulin. The bacterially produced insulin created by Genentech and marketed by Eli Lilly revolutionized the treatment of diabetes, as it produced fewer immune reactions and its supply no longer depended on the availability of animals.

In 1996, Genzyme Transgenics (which in 2002 became GTC Biotherapeutics) created a transgenic goat that produced milk containing a cancer-fighting protein. It soon created additional transgenic animals that could produce specific human proteins to treat human disease. The ability to produce human hormones, enzymes, and other therapeutic products has decreased the risk of disease transmittal from donors to recipients of human products, increased supply, decreased immune reactions, and decreased the variability between medication batches that had been seen in the past.

In the 1990s, scientists sought to develop genetically modified plants and crops, including genetically engineered foods. By 1992, the first plant designed for human consumption (the Flavr Savr tomato) was approved for commercial production by the US Department of Agriculture. In 1994, the European Union approved genetically modified tobacco in France. After these genetically modified crops gained approval, genetically engineered plants and other organisms became more widespread in the United States and reached supermarket shelves. It has been estimated that more than 75 percent of food products on store shelves may contain at least a small quantity of genetically engineered crops.

The Human Genome Project (1990–2003), a collaborative international scientific research initiative spearheaded by the National Institutes of Health, advanced genetic engineering by its publication of human DNA sequencing data. These data allowed scientists to learn more about the physical and functional aspects of genes and DNA. By its completion, the Human Genome Project had fully sequenced the human genome and provided a basic genetic road map for scientists to find human DNA segments of interest.

During the 1900s, scientists also used genetic engineering technology to develop numerous varieties of investigational organisms with very specific characteristics for use in research. Some genetically modified organisms were used to learn more about the natural progression of particular diseases. Others were created to test experimental therapies before moving to humans. These genetically modified organisms have helped scientists learn more about genetic disease, cancer, aging, and other chronic diseases.

In academic and industry laboratories, modern genetic engineering continues to solve problems related to health, disease, industry, and agriculture. Additional applications in humans and human disease have been assisted by government-funded initiatives such as the Human Genome Project. Although controversial at times, genetic engineering is a modern tool to be used in addressing a wide range of problems.

How It Works

Although the types of organisms modified vary substantially in genome size and structure, all genetic engineering involves several general steps: identifying the desired feature or end application, isolating the gene segment that codes for the feature, inserting the gene segment into a vector, and adding it to the target organism, a process called transformation.

Identification. To create genetically modified organisms that will meet a specific need or solve a particular issue, the best way to engineer a solution must be determined. For example, if a large oil spill required cleanup, the first step would be to determine the type of organism and the desired features that would be most effective at removing the spilled oil. Issues to consider in solving a problem through genetic engineering include the desired size and type of organism to be modified, the availability of desired characteristics or features with a known DNA segment, and the possible positive and negative environmental impact resulting from a modified organism.

Isolation of the Proper Gene Segment. To modify an organism through insertion of a gene or DNA segment, the specific DNA segment in the donor organism must be known and be able to be effectively removed from its host genome. In some cases, the DNA segment coding for the desired characteristic is known and available because of previous scientific work. In other cases, this step can be very labor intensive and require long-term research.

After the DNA segment is identified, a particular recombinant technique, often a restriction enzyme, is used to cut the desired gene or DNA segment out of the donor organism and move it into a vector. Depending on the genetic engineering requirements, other techniques such as polymerase chain reaction or agarose gel electrophoresis can be used to isolate a gene or gene segment.

Insertion. Insertion is the genetic engineering step during which the desired gene or DNA segment is integrated into the vector. In this step, restriction enzymes are used to cut the vector open in a particular place so that the desired gene or DNA segment can attach itself to the vector. Then a special enzyme glue called ligase is used to attach the DNA segment to the vector. The most commonly used vectors in genetic engineering are circular form of DNA called bacterial plasmids; however, the type of vector used for a particular application depends on the size of the gene or segment being moved and the organism being modified.

Transformation. The next step of genetic engineering is called transformation. During this step, the desired gene or DNA segment is introduced and successfully added to the organism being modified. A variety of methods can be used to send the vector containing the desired DNA segment into the organism being modified in such a way that the new genetic information is added to the organism's standard genes. These methods include microinjection, use of a gene gun, electroporation, or use of viruses. In each of these methods, the vector carrying the desired genetic segment is forced into the new cells of the organism being modified. Completion of the transformation step relies on testing that determines whether the inserted DNA segment is producing the desired effect or trait in the newly modified organism.

CRISPR. A specific method of genetic engineering, known as CRISPR (clustered regularly interspaced short palindromic repeats) or CRISPR-Cas9, was developed in the first decades of the twenty-first century and was soon viewed as a revolutionary technique. The process is based on segments of DNA, also called CRISPR, from microorganisms including certain bacteria that are able to manipulate the DNA of invading viruses. The enzyme Cas9 and a segment of guide RNA (gRNA) are used as scissors on the molecular level to cut DNA at precise points, allowing fine control of gene editing. The process allowed for much faster and successful genetic engineering than previous methods, opening up the possibility of a much wider application of genetic modification.

Applications and Products

Genetic engineering has far-reaching applications in food production, industry, medicine, and research.

Crops. One of the most widespread but also most controversial uses of genetic engineering is in the creation of genetically modified crops and food. The goal of genetic modification varies from crop to crop. Soybeans have been modified with a DNA segment conveying resistance to herbicides sprayed over fields to kill weeds growing amid the soybeans. The Flavr Savr tomato was engineered to decrease ripening time and increase shelf life. Varieties of rice and corn have been engineered using DNA segments for other plant genomes to have increased levels of vitamins.

From the first commercially grown genetically engineered product for human consumption (the Flavr Savr tomato), adoption of genetically engineered crops in the United States has increased quickly. By 2020, according to data from the US Department of Agriculture's Economic Research Service, more than 90 percent of the cotton, corn, and soybeans planted in the United States came from genetically engineered seeds (herbicide-tolerant, insect-resistant, or both).

Supporters of genetically modified crops feel that the plants can increase food production to meet the world's needs using lower amounts of pesticides and increasing farmer profits. Opponents of genetically engineered crops are concerned about perceived safety issues regarding food produced from these crops, ecological issues around increased use of herbicides, contamination between genetically modified and naturally grown crops because of cross-pollination of fields, and economic difficulties dealing with patents on genetically modified crops.

Livestock. Although farmers have bred particular varieties of livestock such as cows, goats, chickens, and sheep for thousands of years to maximize desirable qualities, genetic engineering allows a more rapid introduction of specific qualities that may or not occur naturally in the animals. The benefits of genetically engineered livestock are numerous and affect the producers, environment, and consumers. Producers benefit by having disease-resistant, increasingly productive, or fast-growing animals. For example, the gene responsible for regulating milk production in cows can be modified to increase milk production. Also, if animals are engineered to have milder waste, the environment will benefit. The FDA has reviewed genetically modified pigs that are better able to digest and process phosphorus in ways that release up to 70 percent less phosphorus in their waste. Consumers benefit from more nutritious, vitamin-enriched meat, as in the case of pigs that are engineered to produce omega-3 fatty acids through the expression of a roundworm gene.

Many of the concerns that apply to crops also apply to livestock. In 2015, the FDA stated that a type of salmon called AquAdvantage, genetically modified to grow twice as fast as conventional Atlantic salmon, was safe for human consumption, the first time a genetically engineered meat was approved by the organization. The FDA has placed several genetically modified animals under review in a category called food-drug. The FDA considers a modified DNA segment to be like a drug and is regulating transgenic organisms in the same way it oversees animals that receive growth hormones or antibiotics. In 2020 the FDA approved pigs that were modified to eliminate an allergen that affects many people for human consumption, and in early 2022 the agency approved beef cattle for consumption that had been modified using the CRISPR method to have short hair enabling greater sustainability in hotter weather.

Diagnosis. Genetic engineering has allowed the development of faster, cheaper, and more accurate diagnostic tests for certain diseases to be used both in the laboratory and in the body. The tests based on genetic engineering are used to identify infectious diseases, hormonal changes, pregnancies, cancer, and other diseases and conditions. For example, a series of faster and more accurate tests for the presence of the human immunodeficiency virus (HIV) have been developed based on genetically modified HIV antigens. Other tests can diagnose diseases by detecting particular substances in specific locations in the body. These exams rely on genetically modified antibodies with markers that can be injected into the body.

Medications. The use of genetically modified organisms to produce human hormones, enzymes, vaccines, and medications has revolutionized the pharmaceutical industry. Since 1982, when Genentech's biosynthetic human insulin was introduced, the ability to manufacture new products in a controlled environment instead of collecting similar substances from the limited supply of human and animal sources has led to more readily available, effective, and reliable medications. Products include human growth hormone to treat children with insufficient growth, plasminogen activator to dissolve blood clots, and erythropoietin to treat low blood iron (anemia). In 1994, genetic engineering also led to innovative treatments for rare genetic disorders such as Gaucher disease with the production of specific human enzymes in genetically modified Chinese hamster ovary cells. The point of this enzyme replacement therapy is to replace the enzyme that the affected individuals are missing through intravenous injections of genetically engineered human enzymes. In multiple situations, the use of genetically engineered organisms to create medications has saved lives and decreased the burden of disease in ways that could not be imagined before. Future applications of genetic engineering in medicine are likely to focus on the creation of better medications for life-threatening indications.

Genetic engineering led to development of effective vaccines against COVID-19 in 2020. Researchers used genetically engineered messenger ribonucleic acid (mRNA) to teach human cells to make a harmless piece of the spike protein found on the surface of the virus. This teaches the immune system to recognize that the spike protein is foreign. The body produces antibodies that protect against the coronavirus that causes the illness. If a fully vaccinated individual is infected with the virus, the body's immune system already knows how to produce the necessary antibodies and can quickly mount a defense. While mRNA research had been taking place for decades, this was the first successful use of this form of genetic engineering to create a vaccine for widespread use. Human trials of mRNA vaccines to fight cancer began about 2011 and were ongoing. Researchers were working to apply the process to vaccines against other illnesses including influenza.

Disease Cures. Genetic engineering made it possible to develop gene therapy. Genetic diseases are inherited conditions that occur because of one or more genetic changes or mutations that prevent the correct functioning of a particular gene. Most genetic diseases do not have a treatment or cure. However, with genetic engineering techniques, scientists hope that they will be able to transform an affected individual's mutated gene into a working gene by replacing it with a functional copy of the gene. Gene therapy has shown some success in helping individuals with severe combined immunodeficiency (SCID), hemophilia type B, and several other genetic diseases, and even has been applied to cancer. However, this type of treatment is still under investigation to determine if it can safely and permanently cure genetic conditions, and other concerns also remain, including ethoeconomic issues over the potential high cost and limited availability of effective treatments.

Research. Genetic engineering and genome sequencing have been used to improve investigative techniques through the ability to manipulate organisms on a basic, genetic level. In genetic research, genetic engineering techniques have allowed scientists to create mice and other organisms affected by a specific gene change for detailed study of a specific genetic disease. For example, a genetically modified mouse that lacks the gene to produce amyloids has been used to study Alzheimer's disease. On a broader scale, genetic engineering allows detailed analysis of an organism's structure, function, and development. Through the insertion of a marker in or near a gene coding for a product of interest, scientists can track the location of that gene's product over time.

Organ Transplantation. Researchers have developed some animals in hopes of improving the chances of individuals who require organ transplants. The amount of available organs falls far short of meeting the demand. Moreover, the recipient's immune system must be suppressed to reduce chances of the body rejecting the donor organ. This has led to development of pigs genetically engineered to allow their organs to be transplanted into humans and not be rejected. This process, called xenotransplantation, has been used several times. In October 2021 surgeons implanted a kidney grown in a genetically altered pig into a human patient; it worked normally for several days. In January 2022 a man with severe heart disease received a heart from a genetically altered pig; he lived for a month before he died of unknown causes.

Industrial Applications. Genetically engineered organisms are used in several manufacturing arenas in production, processing, and waste removal. Most industrial applications of biotechnology are based on naturally occurring processes using modified bacteria, yeast, and other small organisms to digest, transform, and synthesize natural materials from one form into another. More specifically, genetically modified microorganisms have been used to produce industrial chemicals such as ethylene oxide (for making plastics), ethylene glycol (antifreeze), and alcohol. Bacteria have also been engineered to remove toxic wastes from the environment, for example, the varieties of genetically engineered bacteria that consume oil by chemically transforming its compounds into usable basic molecules. Future directions in industry include production of textile fibers, fuels, plastics, and other industrial chemicals out of industrial wastes or raw materials.

Careers and Course Work

Courses in molecular genetics, biochemistry, human genetics, developmental biology, cell biology, microbiology, biological systems engineering, and biotechnology are the foundational requirements for students interested in pursuing careers in genetic engineering. Depending on the student's desired area of study, courses in animal husbandry or medicine might be required. A bachelor's degree in biology, chemistry, applied biotechnology, or genetics is appropriate preparation for graduate work in genetic engineering. In most circumstances a master's degree, medical degree, or doctorate is necessary for the most advanced career opportunities in both academia and industry. However, technician and laboratory roles for those without advanced degrees are often available.

Other career possibilities include marketing and sales staff for pharmaceutical companies, doctors and nurses involved in prenatal genetic testing, genetic ethicists, and genetic counselors. Whether students pursue a scientific, academic, or socially oriented position, they should take a variety of courses beyond the natural sciences to be aware of cultural and societal issues surrounding genetic engineering.

Social Context and Future Prospects

Genetic engineering has already altered the course of agriculture, industry, and medicine with its life-changing applications. Crops have been modified so that they are more nutritious and naturally produce pesticides. Life-saving medications made of human hormones integrated into bacteria are widely available in consistent and purified forms. Bacteria that convert toxic chemicals into harmless basic elements have been developed. Great strides have been made in using gene therapy to cure genetic diseases. Much of the future of genetic engineering will be marked by further refinement of these applications and processes, as well as by unforeseeable breakthroughs made possible by future technological development. However, these significant scientific strides also come with important ethical questions and safety concerns.

Environmentalists are concerned about the impact of genetically modified crops on ecosystems, in particular whether the genes introduced into genetically modified crops will be transferred to conventional crops through cross-pollination. Some researchers express concern that the true impact of GMOs is untested, and that widespread availability of such organisms should be delayed until more data is collected.

Despite general scientific consensus that GMOs as currently produced pose no health risks to humans, some individuals and organizations strongly protest otherwise. While many such opponents cross into the realm of conspiracy theories, some legitimate organizations continue to pose questions. Advocacy groups such as Greenpeace and the World Wildlife Fund are concerned about the safety of genetically modified food and feel that the available data do not prove that there are no risks to human health from consumption. Despite statements from the Royal Society of Medicine and the US National Academy of Sciences in support of the safety of such foods, these groups have called for additional and more rigorous testing.

Other countries have significant concerns about the safety of genetically modified foods. The European Union regulates genetically modified food imported from other nations, including the United States. In 2015 Venezuela banned the growing of genetically modified crops. India issued a moratorium on the cultivation of genetically modified foods in 2009 pending an investigation into safety concerns. In December 2014 India's Genetic Engineering Appraisal Committee approved twelve genetically modified crops for experimental trials to gather more information on their safety and utility, but as of 2022 farmers were still not permitted to grow GM food crops. Other countries such as Japan, Russia, and Zambia have also registered concerns over the safety of genetically modified foods.

There is significantly less controversy over the use of genetically modified organisms in industrial production and medicines. However, the use of genetic engineering techniques for human gene therapy and related applications has touched off a firestorm of ethical debate. Controversy continues to flare up on issues including the ethoeconomic issues of genetic testing, the potential for designer babies, and the possibility of body enhancement through genetics, as well as over the general ethical and religious implications of altering the human genome at any level. These debates are complicated by a lack of cohesive regulation regarding human genetic engineering.

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