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Pharmacology => Drug => Genetic Engineering
Genetic Engineering
INTRODUCTION
Genetic Engineering, alteration of an organism's genetic, or hereditary, material to eliminate undesirable characteristics or to produce desirable new ones. Genetic engineering is used to increase plant and animal food production; to diagnose disease, improve medical treatment, and produce vaccines and other useful drugs; and to help dispose of industrial wastes. Included in genetic engineering techniques are the selective breeding of plants and animals, hybridization (reproduction between different strains or species), and recombinant deoxyribonucleic acid (DNA).
SELECTIVE BREEDING
The first genetic engineering technique, still used today, was the selective breeding of plants and animals, usually for increased food production. In selective breeding, only those plants or animals with desirable characteristics are chosen for further breeding. Corn has been selectively bred for increased kernel size and number and for nutritional content for about 7,000 years. More recently, selective breeding of wheat and rice in an effort called the green revolution has helped supply the world's ever-increasing need for food.
Cattle and pigs were first domesticated about 8,000 years ago and through selective breeding have become main sources of animal food for humans. Dogs and horses have been selectively bred for thousands of years for work and recreational purposes, resulting in more than 130 different dog breeds and 100 different horse breeds.
HYBRIDIZATION
Hybridization (cross-breeding) may involve different strains of a species (that is, members of the same species with different characteristics) or members of different species in an effort to combine the most desirable characteristics of both. For at least 3,000 years, female horses have been bred with male donkeys to produce mules, and male horses have been bred with female donkeys to produce hinnies, for use as work animals.
RECOMBINANT DNA
In recent decades, genetic engineering has been revolutionized by a technique known as recombinant DNA, or gene splicing, which scientists use to directly alter genetic material. Genes consist of the molecule DNA. In recombinant DNA, one or more genes of an organism are introduced to a second organism. If the second organism incorporates the new DNA into its own, recombined DNA results. In humans, recombinant DNA is the basis of gene therapy, in which DNA is introduced into body, or somatic cells, where it may alter their genetic makeup. These alterations cannot be passed to future generations since sperm and eggs, or germ cells, are not affected.
Specific genes and their DNA direct an organism's characteristics through the formation of specific proteins such as enzymes and hormones. Proteins perform vital functions-for example, enzymes initiate many of the chemical reactions that take place within an organism, and hormones regulate various processes such as growth, metabolism, and reproduction. Recombinant DNA technology essentially alters the characteristics of an organism by changing its protein makeup.
° Techniques
Recombinant DNA techniques have transformed genetic engineering in plant and animal food production, industry, and medicine. In most cases, DNA cannot be transferred directly from its original organism, known as the donor, to the recipient organism, known as the host. Instead, the donor DNA must be cut and recombined with a matching fragment of DNA from a vector-that is, an organism that can carry the donor DNA into the host. The host organism is often a rapidly multiplying microorganism such as a harmless bacterium, which serves as a factory where the recombined (recombinant) DNA can be cloned (that is, duplicated) in large quantities. The subsequently produced protein can then be removed from the host, purified, and used as a genetically engineered product in humans, other animals, plants, or bacteria or viruses. The naked DNA can be introduced directly into an organism by techniques such as injection through the cell walls of plants or into the fertilized egg of an animal. Plants and animals that develop from a cell into which new DNA has been introduced are called transgenic organisms.
A related technique performed specifically with animals is known as cloning. In cloning, scientists remove the DNA-containing nucleus from a female's egg and replace it with a nucleus from a different animal of the same species. The scientists then place the egg in the uterus of a third animal. The result, first demonstrated by the birth of a cloned sheep named Dolly in 1997, is the birth of an animal that is nearly genetically identical to the animal from which the nucleus was obtained. Such an animal is genetically unrelated to the surrogate mother. Cloning is still in its infancy, but it may pave the way for improved farm animals and medical products.
° Food Production
Recombinant DNA has been used to combat one of the greatest problems in plant food production: the destruction of crops by plant viruses. For example, by transferring the protein-coat gene of the zucchini yellow mosaic virus to squash plants that had previously sustained great damage from the virus, scientists were able to create transgenic squash plants with immunity to this virus. Scientists also have developed transgenic potato and strawberry plants that are frost-resistant; potatoes, corn, tobacco, and cotton that resist attacks by certain insect pests; and soybeans, cotton, corn, and oilseed rape (the source of canola oil) that have increased resistance to certain weed-killing chemicals called herbicides.
Similarly, in animal food production, the growth hormone gene of rainbow trout has been transferred directly into carp eggs. The resultant transgenic carp produce both carp and rainbow trout growth hormones and grow to be one-third larger than normal carp. Other fish that have been genetically engineered include salmon, which have been modified for faster growth, and trout, which have been altered so that they are more resistant to infection by a blood virus.
Recombinant DNA also has been used to clone large quantities of the gene responsible for the cattle growth hormone bovine somatotropin (BST) in the bacterium Escherichia coli. The hormone is then extracted from the bacterium, purified, and injected into dairy cows, increasing their milk production by 10 to 15 percent.
° Industry
Gene transfers also have been applied in the management of industrial wastes. Genetically altered bacteria can be used to decompose many forms of garbage and to break down petroleum products. Recombinant DNA technology also can be used to monitor the breakdown of pollutants. For example, naphthalene, an environmental pollutant present in artificially manufactured soils, can be broken down by the bacterium Pseudomonas fluorescens. To monitor this process, scientists transferred a light-producing enzyme called luciferase, found in the bacterium Vibrio fischeri, to the Pseudomonas fluorescens bacterium. The genetically altered Pseudomonas fluorescens bacterium produces light in proportion to the amount of its activity in breaking down the naphthalene, thus providing a way to monitor the efficiency of the process (see Bioremediation).
° Medicine
In 1982 the United States Food and Drug Administration (FDA) approved for the first time the medical use of a recombinant DNA protein, the hormone insulin, which had been cloned in large quantities by inserting the human insulin gene in Escherichia coli bacteria. Previously, this hormone, used by insulin-dependent people with diabetes mellitus, had been available only in limited quantities from hogs.
Since that time, the FDA has approved other genetically engineered proteins for use in humans, including two cloned in hamster cell cultures: tissue plasminogen activator (tPA), an enzyme used to dissolve blood clots in people who have suffered heart attacks, and erythropoetin, a hormone used to stimulate the production of red blood cells in people with severe anemia. Another important genetically engineered drug is interferon, a chemical that is produced by the body in tiny amounts. Engineered interferon is used to fight viral diseases and as an anticancer drug.
Scientists also have employed recombinant DNA techniques to produce medically useful human proteins in animal milk. In this procedure, the human gene responsible for the desired protein is first linked to specific genes of the animal that are active only in its mammary (milk-producing) glands. The egg of the animal is then injected with the linked genes. The resulting transgenic animals will have these linked genes in every cell of their body but will produce the human protein only in their milk. The human protein is finally extracted from the animal's milk for use as medicine. In this way, sheep's milk is used to produce alpha-1-antitrypsin, an enzyme used in the treatment of emphysema; cow's milk is used to produce lactoferrin, a protein that combats bacterial infections; and goat's milk is used as yet another way to produce tPA, the blood-clot-dissolving enzyme also cloned in hamster cell
cultures.
Recombinant DNA technology also is used in the production of vaccines against disease. A vaccine contains a form of an infectious organism that does not cause severe disease but does cause the body's immune system to form protective antibodies against the organism. When a person is vaccinated against a viral disease, the production of antibodies is actually a reaction to the surface proteins of the coat of the virus. With recombinant DNA technology, scientists have been able to transfer the genes for some viral-coat proteins to the vaccinia, or cowpox, virus, which was used against smallpox in the first efforts at vaccination, and which gave the process its name. Vaccination with genetically altered vaccinia is now being used against hepatitis, influenza, and herpes simplex viruses. Genetically engineered vaccinia is considered safer than using the disease-causing virus itself and is equally as effective.
Gene therapy, in which a healthy gene can be directly inserted into a person with a malfunctioning gene, is perhaps the most revolutionary and promising of recombinant DNA technologies, but many problems remain to be solved in getting the healthy gene into human cells. Although the use of gene therapy has been approved in more than 100 clinical trials for diseases such as cystic fibrosis, emphysema, muscular dystrophy, and adenosine deaminase deficiency, in some instances with promising results, there have as yet been no cures.
PATENTING RECOMBINANT DNA PRODUCTS
It takes an average of seven to nine years and an investment of about $55 million to develop, test, and market a new genetically engineered product. Because of this great cost, companies have sought to patent the results of their discoveries. In 1980 the Patent and Trademark Office of the U.S. Department of Commerce issued its first patent on an organism that had been produced with recombinant DNA. The patent was for a so-called oil-eating bacterium that could be used in the bioremediation (that is, the cleaning up by natural means) of oil spills from ships and storage tanks. Since then, hundreds of patents have been granted for genetically altered bacteria, viruses, and plants. In 1988 the first patent was issued on a transgenic animal, a strain of laboratory mice whose cells were engineered to contain a cancer-predisposing gene. The mice are used to test low doses of suspected carcinogens, or cancer-causing substances, and to test the effectiveness of anticancer therapies.
CONTROVERSIES
Public reaction to the use of recombinant DNA in genetic engineering has been mixed. The production of medicines through the use of genetically altered organisms has generally been welcomed. However, critics of recombinant DNA fear that the pathogenic, or disease-producing, organisms used in some recombinant DNA experiments might develop extremely infectious forms that could cause worldwide epidemics. In an effort to prevent such an occurrence, the National Institutes of Health (NIH) in the United States has established regulations restricting the types of recombinant DNA experiments that can be performed using such pathogens. In Canada, recombinant DNA products are regulated by various government departments, including Agriculture and Agri-Food Canada, Health Canada, Fisheries and Oceans Canada, and Environment Canada.
Transgenic plants also present controversial issues. Environmentalists fear that the transgenic plants may interbreed with weeds, producing weeds with unwanted characteristics, such as resistance to herbicides. An example of such interbreeding has been demonstrated in experiments involving transgenic oilseed rape. Environmentalists also argue that, due to natural selection, insects quickly develop resistance to plants that have been engineered to incorporate biological pesticides.
Allergies are another potential problem of genetically engineered food crops. Allergens can be transferred from one food crop to another through genetic engineering. In an attempt to increase the nutritional value of soybeans, a genetic engineering firm experimentally transferred a Brazil nut gene producing a nutritious protein into the soybean plant. However, when a study found that the genetically engineered soybeans caused an allergic reaction in people sensitive to Brazil nuts, the project was canceled.
Animal rights groups have argued that the production of transgenic animals is harmful to animals. Genetically engineered fish raise problems because of the ability of fish to swim far from their place of origin. Engineered fish are typically confined to fish farms, but some escape into rivers and streams, where they may interbreed with other fish that have not been genetically altered. Some experts fear that this process may change the characteristics of wild fish in unpredictable and possibly undesirable ways. A related concern is that engineered fish may compete with wild fish for food and replace wild fish in some areas.
The use of bovine growth hormone to increase the milk yield of dairy cows is particularly controversial. Some critics question the safety of BST in regard to both the cows that are injected with it and the humans who drink the resulting milk. In the United States, a large percentage of dairy cows are treated with BST, but in Canada, BST cannot legally be sold. Scientists at Health Canada rejected the legalization of BST in 1999, based on evidence that BST causes health problems for cows. In particular, the Canadian scientists found that BST increases a cow's likelihood of developing mastitis, or infection of the udder, and it also makes cows more susceptible to infertility and lameness. Nevertheless, the scientists consider the milk obtained from cows injected with BST to be safe for human consumption.
Some critics object to the patenting of genetically altered organisms because it makes the organisms the property of particular companies. For example, Costa Rica has enacted laws to prohibit the patenting of genes of native Costa Rican species by drug companies in other countries. To date, no laws are in place in the United States regulating the use of cloning technology, and some people fear the prospect of human cloning. If this technology remains unregulated, critics fear that it will provide the ability to create an "improved" human being with characteristics predetermined according to a scientist's particular bias.
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