Biotechnology and genetic engineering

Definitions: Biotechnology is the use of living organisms, or substances obtained from such organisms, to produce products or processes of value to humankind; genetic engineering is the manipulation of deoxyribonucleic acid (DNA) and the transfer of genes or gene components from one species to another.

Biotechnology has made tremendous advances possible in human and veterinary medicine, agriculture, food production, and other fields. However, debates continue regarding the potential of biotechnology, in particular genetic engineering, to produce organisms that may disrupt ecosystems, negatively affect human health, or be used in ethically inappropriate ways.

The term “biotechnology” is relatively new in the twenty-first century, but the practice of biotechnology is as old as civilization. Civilization did not evolve until humans learned to produce food crops and domestic livestock through the controlled breeding of selected plants and animals. The pace of modifying organisms accelerated during the twentieth century. Through carefully controlled breeding programs, plant architecture and fruit characteristics of crops were modified to facilitate mechanical harvesting. Plants were developed to produce specific drugs or spices, and microorganisms were selected to produce antibiotics such as penicillin and other useful medicinal and food products.

The ability to utilize artificial media to propagate plants led to the development of a technology called tissue culture. In some plant tissue culture, the tissue is treated with the proper plant hormones to produce masses of undifferentiated cells called callus tissue, which can also be separated into single cells to establish a cell suspension culture. Specific drugs or other chemicals can be produced with callus tissue and cell suspensions, or this tissue can be used to regenerate entire plants. Tissue culture technology is used as a propagation tool in commercial-scale plant production.

Numerous advances have also occurred in animal biotechnology. Artificial insemination, the process in which semen is collected from the male animal and deposited into the female reproductive tract through artificial techniques rather than natural mating, emerged as a practical procedure around the onset of the twentieth century, although as early as 1784, Italian biologist Lazzaro Spallanzani successfully inseminated a dog. Males in species such as cattle can sire hundreds of thousands of offspring through artificial insemination, whereas they could sire only fifty or fewer through natural means.

Embryo transfer is a technique used in humans to facilitate conception after in vitro fertilization, a procedure in which eggs are surgically removed from the ovaries and manually combined with sperm in a laboratory. Once fertilization and cell division are confirmed, the embryos are placed in the uterus. The eggs may be supplied by a woman who is unable to conceive naturally but who can carry a child to term. They may also be provided by an egg donor to a woman who cannot otherwise get pregnant; or a woman who cannot carry a child to term may supply eggs to be fertilized in vitro and implanted in a surrogate mother. Superovulation is the process in which females that are to provide eggs are injected with hormones to stimulate increased egg production. Embryo splitting is the mechanical division of an embryo into identical twins, quadruplets, sextuplets, and so on. Both superovulation and embryo splitting have made routine embryo transfers possible. In livestock, embryo transfer technology is used to combine the sperm from a superior male animal and several eggs, each of which can then be split into several offspring, from a superior female. The resulting embryos can then be transferred to the reproductive tracts of inferior surrogate females.

Recombinant DNA Technology

Biotechnological advances have enabled scientists to tap into the world gene pool. This technology has great potential, and its full magnitude is far from being fully realized. Theoretically, it is possible to transfer one or more genes or gene segments from any organism in the world into any other organism. Because genes ultimately control how an organism functions, gene transfer can have a dramatic impact on agricultural resources and human health.

Research has provided the means by which genes can be identified and manipulated at the molecular and cellular levels. This identification and manipulation depend primarily on recombinant DNA technology. In concept, recombinant DNA methodology is fairly easy to comprehend, but in practice it is rather complex. The genes in all living cells are very similar in that they are all composed of the same chemical, deoxyribonucleic acid, or DNA. The DNA of all cells, whether from bacteria, plants, lower animals, or humans, is very similar, and when DNA from a foreign species is transferred into a different cell, it functions exactly as the native DNA functions; that is, it codes for protein.

The simplest protocol for this transfer involves the use of a vector, usually a piece of circular DNA called a plasmid, which is removed from a microorganism such as a bacterium and cut open by an enzyme called a restriction endonuclease or restriction enzyme. A section of DNA from the donor cell that contains a previously identified gene of interest is cut out from the donor cell DNA by the same restriction endonuclease. The section of donor cell DNA with the gene of interest is then combined with the open plasmid DNA, and the plasmid closes with the new gene as part of its structure. The recombinant plasmid (DNA from two sources) is placed back into the bacterium, where it will replicate and code for protein just as it did in the donor cell. The bacterium can be cultured and the gene product (protein) harvested, or the bacterium can be used as a vector to transfer the gene to another species, where it will also be expressed. This transfer of genes, and therefore of inherited traits, between different species has revolutionized biotechnology and provides the potential for genetic changes in plants and animals that have not yet been envisioned.

Biotechnology and Agriculture

Biotechnology has had a tremendous impact on agriculture. Traditional breeding programs may be too slow to keep pace with the needs of a rapidly expanding human population. Biotechnology provides a means of developing higher-yielding crops in one-third of the time it takes to develop them though traditional plant breeding programs because the genes for desired characteristics can be inserted directly into a plant without having to go through several generations to establish the trait. Also, there is often a need or desire to diversify agricultural production in a given area, but soil or climate conditions may severely limit the amount of diversification that can take place. Biotechnology can provide the tools to help solve this problem: Crops with high cash value can be developed to grow in areas that would not support unmodified versions of such crops. In addition, biotechnology can be used to increase the cash value of crops, as plants can be developed that can produce new and novel products such as antibiotics, hormones, and other pharmaceuticals.

As public pressure has grown for crop production to be more friendly to the environment, biotechnology has been touted as an important tool for the development of a long-term, sustainable, environmentally friendly agricultural system. Biotechnology is already being used to develop crops with improved resistance to pests. For example, a gene from the bacterium Bacillus thuringiensis (B.t.) codes for an insecticidal protein that kills insects but is harmless to other organisms. When this gene is transferred from the bacterium to a plant, insect larvae are killed if they eat from the leaves or roots of the plant. A number of B.t. plants have been developed, including cotton and potatoes. Crop varieties engineered for improved pest resistance have the potential to reduce reliance on pesticides; however, insect pests have developed resistance to some of these crops.

Biotechnology also plays an important role in the livestock industry. Bovine somatotropin, a hormone that stimulates growth in cattle, is harvested from recombinant bacteria and injected in dairy cattle to enhance milk production. However, questions have arisen as to whether overstimulating milk production is humane or healthy for cows, and fears regarding the health implications for humans consuming milk that contains bovine hormone residues have made many people seek organic dairy products free from artificial hormones. Some countries do not allow the use of these hormones in milk intended for human consumption.

Researchers are exploring the possibilities of genetically engineering animals that can resist disease or produce novel and interesting products such as pharmaceuticals. The cloning of Dolly the sheep in Scotland in 1996 opened a whole new avenue in the use of biotechnology for livestock production. The use of cloning technology in conjunction with surrogate mothers provides the means to produce a whole herd of genetically superior animals in a short period of time. However, reproductive cloning is expensive, its success rate is low, and many cloned animals have been found to be unhealthy and short-lived.

Biotechnology and Medicine

DNA technology also has a direct impact on human health and is used to manufacture a variety of gene products that are utilized in the clinical treatment of diseases. Several human hormones produced by this methodology were in use in 2022. The hormone insulin, for instance, which is used to treat insulin-dependent diabetics, was the first major success in using a product of recombinant technology. Recombinant DNA-produced insulin has been used to treat diabetic patients since 1982. Genetic engineering has also been used to synthesize protropin, a human growth hormone (HGH) employed in the treatment of growth failure conditions such as hyposomatotropism. Without treatment with HGH, people suffering from these conditions do not produce enough growth hormone to achieve a typical adult height.

Somatostatin, another pituitary hormone, has also been produced through recombinant DNA techniques. This hormone controls the release of insulin and HGH. Small proteins called interferons normally produced by cells to combat viral infections have been produced using recombinant DNA methodology, as have some vaccines against viral diseases. Recombivax HB, the first of these vaccines, is used in vaccinating against hepatitis B, an incurable and sometimes fatal liver disease.

The potential for the future application of gene therapy has also been enhanced by advances in biotechnology. Among the forms of gene therapy currently being considered are gene surgery, in which a mutant gene that may or may not be replaced by its normal counterpart is excised from the DNA; gene repair, in which defective DNA is repaired within the cell to restore the genetic code; and gene insertion, in which a normal gene complement is inserted in cells that carry a defective gene.

Gene surgery and gene repair techniques are extremely complex and remain in the experimental stages. Gene insertion can potentially be done in germ-line cells such as the egg or sperm, the fertilized ovum or zygote, the fetus, or the somatic cells (nonreproductive cells) of children or adults. Although zygote therapy holds the most promise, as this technique could eliminate genetic disease, gene insertion in zygotes also represents a means by which traits such as strength or intelligence might be enhanced and the genetic traits of future generations artificially selected, a possibility that raises a host of ethical questions. Germ-line genetic modification has been performed successfully in laboratory animals, but unwanted mutations with serious or lethal consequences have also sometimes resulted.

Gene insertion into somatic cells does not make changes that are passed on to subsequent generations, so it does not present the ethical dilemma that germ-line manipulation does. In this technique, a gene or gene segment is inserted into specific organs or tissues as a treatment for an existing condition. In human clinical trials, somatic gene therapy has shown success in treating advanced melanoma, myeloid disorders, inherited childhood blindness, and severe combined immunodeficiency. However, the carrier molecules used to deliver the therapeutic gene to the target cells have the potential to provoke a serious or fatal immune response in the patient.

Environmental Issues

The potential benefits of biotechnology for human health, agriculture, and the environment are accompanied by potential drawbacks. Since the first recombinant DNA experiments in 1973, numerous social, ethical, and scientific questions have been raised about the possible detrimental effects of genetically engineered organisms on public health and the environment. The major environmental concerns are related to containment, or how to prevent genetically engineered organisms from escaping into the environment.

In the mid-1970s, U.S. scientists invoked a self-imposed moratorium on genetic engineering experiments until the government could establish committees to develop safety guidelines that would apply to all recombinant DNA experimentation in the United States. This resulted in the formulation of guidelines specifying the degree of containment required for various types of genetic engineering experiments. Two types of containment, biological and physical, are addressed by the guidelines. “Physical containment” refers to the methods required to prevent an engineered organism from escaping from the laboratory; “biological containment” refers to the techniques used to ensure that an engineered organism cannot survive outside the laboratory. The guidelines associated with containment, particularly physical containment, are sometimes difficult to monitor and enforce.

Some observers have noted that despite the rigors of the containment guidelines, the possibility remains that an engineered organism will eventually escape into the environment. Should this occur, the organism could cause environmental damage as great as or greater than that caused in the past by the introduction of foreign species to new habitats. For example, the introduction of rabbits to Australia dramatically upset the ecological balance on that continent. Hence field experiments with genetically engineered organisms must be strenuously controlled and monitored.

Although numerous safe field trials have been conducted with genetically engineered organisms, such as B.t. plants, widespread opposition to such practices remains. There appear to be few risks that cannot be ascertained within the laboratory associated with the release of genetically engineered higher plants, but opponents have expressed the fear that engineered genes could possibly be transferred by cross-pollination to other species of plants. Such a transfer could, for example, produce a highly vigorous species of weed. In addition, such gene transfers could potentially result in a plant that produces a toxin that would be detrimental to other plants, animals, or humans.

Because viruses and bacteria are major components of numerous natural biochemical cycles and readily exchange genetic information in a variety of ways, it is even more difficult to envision all the ramifications associated with releasing these genetically altered organisms into the environment. Field testing of genetically engineered organisms will always involve some element of risk, and assessment of the risks of such testing is easier for some species, such as higher plants, than for other species, such as bacteria.

A clear need exists for rigid controls, and minimizing the risks also requires integral cooperation among industry, governments, and regulatory organizations. Under the Cartagena Protocol on Biosafety, which entered into force in 2003, before an importing nation may release living modified organisms (LMOs) into the environment, the country into which the LMO is to be imported must first give its informed consent. The importer must clearly identify the LMO, detail its traits and characteristics, and explain its proper handling, storage, transport, and use.

With advances in the cloning of plants and animals, environmentalists and others have expressed concerns about losses in genetic variability. In nature, species survival is dependent on the genetic variability, or diversity, of the population. Genetic variability obtained through normal sexual reproduction provides a species with the ability to adapt to changes in the environment; because the environment is continually changing, loss of genetic variability usually leads to extinction of the species. Because cloning results in genetically identical individuals, the cloning of large numbers of animals or plants of particular species at the expense of those produced through sexual reproduction can lead to the loss of genetic variability and thus to eventual extinction of those species.

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