The term “genetic engineering” encompasses all techniques involved in the artificial manipulation, modification, and recombination of DNA or other nucleic acid molecules. These techniques are employed to alter organisms or populations of organisms.
Genetic engineering generally refers to recombinant DNA technology, which originated from basic research in microbial genetics. The techniques developed have led to the production of medically important products, including human insulin, human growth hormone, and the hepatitis B vaccine, as well as the development of genetically modified organisms (GMOs), such as disease-resistant plants.
Genetic Engineering and Insulin Production
Initially, the term “genetic engineering” referred to various techniques used to modify or manipulate organisms through heredity and reproduction processes. This included artificial selection and biomedical interventions like artificial insemination, in vitro fertilization (e.g., test-tube babies), cloning, and genetic manipulation. However, by the late 20th century, the term became more closely associated with recombinant DNA technology, where DNA molecules from two or more sources are combined within cells or in vitro, and then inserted into host organisms for propagation.
The possibility of recombinant DNA technology emerged with the discovery of restriction enzymes in 1968 by Swiss microbiologist Werner Arber. A year later, American microbiologist Hamilton O. Smith purified Type II restriction enzymes, which became essential for genetic engineering due to their ability to cleave DNA at specific sites (unlike Type I enzymes, which cleave DNA at random sites). Building on Smith’s work, American molecular biologist Daniel Nathans promoted DNA recombination techniques in 1970-71, demonstrating the utility of Type II enzymes in genetic studies. Genetic engineering based on recombination was pioneered in 1973 by American biochemists Stanley N. Cohen and Herbert W. Boyer, who were among the first to cut DNA into fragments, reassemble different fragments, and insert the new genes into the bacterium E. coli, allowing these genes to be passed on to future generations.
Process and Techniques
Most recombinant DNA technology involves inserting foreign genes into plasmids of common laboratory strains of bacteria. Plasmids are small rings of DNA that do not form part of the bacterial chromosome (the organism’s primary genetic information repository). However, plasmids can direct protein synthesis and, like chromosomal DNA, are reproduced and passed on to the bacterium’s progeny. Thus, by incorporating foreign DNA (e.g., a mammalian gene) into a bacterium, researchers can obtain almost unlimited copies of the inserted gene. Furthermore, if the inserted gene is functional (i.e., if it directs protein synthesis), the modified bacterium will produce the protein specified by the foreign DNA.
A later generation of genetic engineering techniques, emerging in the early 21st century, focused on gene editing. Gene editing, based on a technology known as CRISPR-Cas9, allows researchers to customize the genetic sequence of a living organism by making very specific changes to its DNA. Gene editing has a wide range of applications and is used for the genetic modification of crops, livestock, and laboratory model organisms (e.g., mice).
Applications of Gene Editing
Gene editing has advanced the understanding of many theoretical and practical aspects of gene function and organization. Through recombinant DNA techniques, bacteria capable of synthesizing human insulin, human growth hormone, alpha interferon, a hepatitis B vaccine, and other medically useful substances have been created. Plants can be genetically modified to enable them to fix nitrogen, and genetic diseases can potentially be corrected by replacing dysfunctional genes with normally functioning ones.
Toxin-producing genes that kill insects have been introduced into several plant species, including corn and cotton. Bacterial genes that confer herbicide resistance have also been introduced into crop plants. Other genetic engineering attempts in plants have aimed to improve the plant’s nutritional value.
Controversy and Ethical Issues
In 1980, “new” microorganisms created through recombinant DNA research were deemed patentable, and in 1986, the U.S. Department of Agriculture approved the sale of the first genetically altered living organism: a virus used as a vaccine against pseudorabies, from which a single gene had been cut. Since then, several hundred patents have been granted for genetically modified bacteria and plants. However, patents on genetically modified organisms, particularly crops and other foods, were a contentious issue and remained so in the early 21st century.
There has been particular concern about genetic engineering due to fears that it could result in the introduction of unfavorable and potentially dangerous traits in microorganisms that were previously free of them—for example, antibiotic resistance, toxin production, or a tendency to cause diseases. Indeed, the possibilities for the misuse of genetic engineering are enormous. There was great concern about genetically modified organisms, especially modified crops, and their impact on human and environmental health. For example, genetic manipulation could potentially alter the allergenic properties of crops. Additionally, it was unclear whether some genetically modified crops, such as golden rice, fulfilled the promise of better health benefits. The release of genetically modified mosquitoes and other organisms into the environment also raised concerns.
In the 21st century, significant progress in developing gene editing tools brought new urgency to discussions about the ethical and social implications surrounding the genetic engineering of humans. The application of gene editing in humans generated significant ethical concerns, particularly regarding its potential use to alter traits such as intelligence and beauty.
More practically, some researchers attempted to use gene editing to alter genes in human sperm, allowing edited genes to be passed on to future generations, while others sought to alter genes that increase the risk of certain types of cancer to reduce cancer risk in offspring. However, the impacts of genetic editing on human genetics were unknown, and regulations to guide its use were largely lacking.